Is Mohammed a Strategic Leader?

DTIC Science & Technology

2011-03-01

followers began to raid caravans running trade between Mecca, Medina, and Syria. He had no income other than booty from the spoils of war. He established...tide of the battle turned when his lead swordsmen and archers abandoned their posts to gather booty thereby allowing the Meccan cavalry to flank the

Walking boot assembly

NASA Technical Reports Server (NTRS)

Vykukal, H. C.; Chambers, A. B.; Stjohn, R. H. (Inventor)

1977-01-01

A walking boot assembly particularly suited for use with a positively pressurized spacesuit is presented. A bootie adapted to be secured to the foot of a wearer, an hermetically sealed boot for receiving the bootie having a walking sole, an inner sole, and an upper portion adapted to be attached to an ankle joint of a spacesuit, are also described.

The "booty call": a compromise between men's and women's ideal mating strategies.

PubMed

Jonason, Peter K; Li, Norman P; Cason, Margaret J

2009-01-01

Traditionally, research on romantic and sexual relationships has focused on one-night stands and monogamous pairs. However, as the result of men and women pursuing their ideal relationship types, various compromise relationships may emerge. One such compromise is explored here: the "booty call." The results of an act-nomination and frequency study of college students provided an initial definition and exploration of this type of relationship. Booty calls tend to utilize various communication mediums to facilitate sexual contact among friends who, for men, may represent low-investment, attractive sexual partners and, for women, may represent attractive test-mates. The relationship is discussed as a compromise between men's and women's ideal mating strategies that allows men greater sexual access and women an ongoing opportunity to evaluate potential long-term mates.

Dynamical investigations of the multiple stars

NASA Astrophysics Data System (ADS)

Kiyaeva, Olga V.; Zhuchkov, Roman Ya.

2017-11-01

Two multiple stars - the quadruple star - Bootis (ADS 9173) and the triple star T Taury were investigated. The visual double star - Bootiswas studied on the basis of the Pulkovo 26-inch refractor observations 1982-2013. An invisible satellite of the component A was discovered due to long-term uniform series of observations. Its orbital period is 20 ± 2 years. The known invisible satellite of the component B with near 5 years period was confirmed due to high precision CCD observations. The astrometric orbits of the both components were calculated. The orbits of inner and outer pairs of the pre-main sequence binary T Taury were calculated on the basis of high precision observations by the VLT and on the Keck II Telescope. This weakly hierarchical triple system is stable with probability more than 70%.

Evaluations and Future Plans After Casual Sexual Experiences: Differences Across Partner Type.

PubMed

Wesche, Rose; Claxton, Shannon E; Lefkowitz, Eva S; van Dulmen, Manfred H M

2017-03-24

Casual sexual relationships and experiences (CSREs) are common among emerging adults, and their diversity may contribute to variability in their associations with mental health and future romantic relationship development. The present research used multiple regression analyses to examine how CSRE type (casual dating, friends with benefits [FWB], or booty call/one-night stand) is associated with short-term outcomes of these experiences, including positive and negative evaluations, plans to start a romantic relationship with a CSRE partner, and general plans for future CSREs. College students and non-college-attending emerging adults (N = 192, 80% female, mean age = 22.09 years) reported on recent sexual encounters through daily diaries collected around an alcohol consumption holiday. Individuals with casual dating partners evaluated their experiences more positively and/or less negatively than individuals with booty calls/one-night stands; these associations were moderated by gender and sexual behavior type. Individuals with casual dating partners were more oriented toward pursuing a romantic relationship with their partners than individuals with FWB or booty calls/one-night stands. However, no association was found between CSRE type and plans for future CSREs in general. Results highlight the diversity of CSREs and suggest that casual dating may be more rewarding than FWB and booty calls/one-night stands, particularly for women.

Searching for Dust around Hyper Metal Poor Stars

NASA Astrophysics Data System (ADS)

Venn, Kim A.; Puzia, Thomas H.; Divell, Mike; Côté, Stephanie; Lambert, David L.; Starkenburg, Else

2014-08-01

We examine the mid-infrared fluxes and spectral energy distributions for stars with iron abundances [Fe/H] <-5, and other metal-poor stars, to eliminate the possibility that their low metallicities are related to the depletion of elements onto dust grains in the formation of a debris disk. Six out of seven stars examined here show no mid-IR excesses. These non-detections rule out many types of circumstellar disks, e.g., a warm debris disk (T <= 290 K), or debris disks with inner radii <=1 AU, such as those associated with the chemically peculiar post-asymptotic giant branch spectroscopic binaries and RV Tau variables. However, we cannot rule out cooler debris disks, nor those with lower flux ratios to their host stars due to, e.g., a smaller disk mass, a larger inner disk radius, an absence of small grains, or even a multicomponent structure, as often found with the chemically peculiar Lambda Bootis stars. The only exception is HE0107-5240, for which a small mid-IR excess near 10 μm is detected at the 2σ level; if the excess is real and associated with this star, it may indicate the presence of (recent) dust-gas winnowing or a binary system.

HD 54272, a classical λ Bootis star and γ Doradus pulsator

NASA Astrophysics Data System (ADS)

Paunzen, E.; Skarka, M.; Holdsworth, D. L.; Smalley, B.; West, R. G.

2014-05-01

We detect the second known λ Bootis star (HD 54272) which exhibits γ Doradus-type pulsations. The star was formerly misidentified as a RR Lyrae variable. The λ Bootis stars are a small group (only 2 per cent) of late B to early F-type, Population I stars which show moderate to extreme (up to a factor 100) surface underabundances of most Fe-peak elements and solar abundances of lighter elements (C, N, O, and S). The photometric data from the Wide Angle Search for Planets (WASP) and All Sky Automated Survey (ASAS) projects were analysed. They have an overlapping time base of 1566 d and 2545 d, respectively. Six statistically significant peaks were identified (f1 = 1.410 116 d-1, f2 = 1.283 986 d-1, f3 = 1.293 210 d-1, f4 = 1.536 662 d-1, f5 = 1.157 22 d-1 and f6 = 0.226 57 d-1). The spacing between f1 and f2, f1 and f4, f5 and f2 is almost identical. Since the daily aliasing is very strong, the interpretation of frequency spectra is somewhat ambiguous. From spectroscopic data, we deduce a high rotational velocity (250 ± 25 km s-1) and a metal deficiency of about -0.8 to -1.1 dex compared to the Sun. A comparison with the similar star, HR 8799, results in analogous pulsational characteristics but widely different astrophysical parameters. Since both are λ Bootis-type stars, the main mechanism of this phenomenon, selective accretion, may severely influence γ Doradus-type pulsations.

VizieR Online Data Catalog: AR Sco VLA radio observations (Stanway+, 2018)

NASA Astrophysics Data System (ADS)

Stanway, E. R.; Marsh, T. R.; Chote, P.; Gaensicke, B. T.; Steeghs, D.; Wheatley, P. J.

2018-02-01

Time series VLA radio observations were undertaken of the highly variable white dwarf binary AR Scorpii. These were analysed for periodicity, spectral behaviour and other characteristics. Here we present time series data in the Stokes I parameter at three frequencies. These were centred at 1.5GHz (1GHz bandwidth), 5GHz (2GHz bandwidth) and 9GHz (2GHz bandwidth). The AR Sco binary is unresolved at these frequencies. In the case of the 1.5GHz data, fluxes have been deconvolved with those of a neighbouring object. (3 data files).

Mechanisms of Alizarin Red S and Methylene blue biosorption onto olive stone by-product: Isotherm study in single and binary systems.

PubMed

Albadarin, Ahmad B; Mangwandi, Chirangano

2015-12-01

The biosorption process of anionic dye Alizarin Red S (ARS) and cationic dye methylene blue (MB) as a function of contact time, initial concentration and solution pH onto olive stone (OS) biomass has been investigated. Equilibrium biosorption isotherms in single and binary systems and kinetics in batch mode were also examined. The kinetic data of the two dyes were better described by the pseudo second-order model. At low concentration, ARS dye appeared to follow a two-step diffusion process, while MB dye followed a three-step diffusion process. The biosorption experimental data for ARS and MB dyes were well suited to the Redlich-Peterson isotherm. The maximum biosorption of ARS dye, qmax = 16.10 mg/g, was obtained at pH 3.28 and the maximum biosorption of MB dye, qmax = 13.20 mg/g, was observed at basic pH values. In the binary system, it was indicated that the MB dye diffuses firstly inside the biosorbent particle and occupies the biosorption sites forming a monodentate complex and then the ARS dye enters and can only bind to untaken sites; forms a tridentate complex with OS active sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hadronic model for the non-thermal radiation from the binary system AR Scorpii

NASA Astrophysics Data System (ADS)

Bednarek, W.

2018-05-01

AR Scorpii is a close binary system containing a rotation powered white dwarf and a low-mass M type companion star. This system shows non-thermal emission extending up to the X-ray energy range. We consider hybrid (lepto-hadronic) and pure hadronic models for the high energy non-thermal processes in this binary system. Relativistic electrons and hadrons are assumed to be accelerated in a strongly magnetised, turbulent region formed in collision of a rotating white dwarf magnetosphere and a magnetosphere/dense atmosphere of the M-dwarf star. We propose that the non-thermal X-ray emission is produced either by the primary electrons or the secondary e± pairs from decay of charged pions created in collisions of hadrons with the companion star atmosphere. We show that the accompanying γ-ray emission from decay of neutral pions, which are produced by these same protons, is expected to be on the detectability level of the present and/or the future satellite and Cherenkov telescopes. The γ-ray observations of the binary system AR Sco should allow us to constrain the efficiency of hadron and electron acceleration and also the details of the radiation processes.

A radio-pulsing white dwarf binary star.

PubMed

Marsh, T R; Gänsicke, B T; Hümmerich, S; Hambsch, F-J; Bernhard, K; Lloyd, C; Breedt, E; Stanway, E R; Steeghs, D T; Parsons, S G; Toloza, O; Schreiber, M R; Jonker, P G; van Roestel, J; Kupfer, T; Pala, A F; Dhillon, V S; Hardy, L K; Littlefair, S P; Aungwerojwit, A; Arjyotha, S; Koester, D; Bochinski, J J; Haswell, C A; Frank, P; Wheatley, P J

2016-09-15

White dwarfs are compact stars, similar in size to Earth but approximately 200,000 times more massive. Isolated white dwarfs emit most of their power from ultraviolet to near-infrared wavelengths, but when in close orbits with less dense stars, white dwarfs can strip material from their companions and the resulting mass transfer can generate atomic line and X-ray emission, as well as near- and mid-infrared radiation if the white dwarf is magnetic. However, even in binaries, white dwarfs are rarely detected at far-infrared or radio frequencies. Here we report the discovery of a white dwarf/cool star binary that emits from X-ray to radio wavelengths. The star, AR Scorpii (henceforth AR Sco), was classified in the early 1970s as a δ-Scuti star, a common variety of periodic variable star. Our observations reveal instead a 3.56-hour period close binary, pulsing in brightness on a period of 1.97 minutes. The pulses are so intense that AR Sco's optical flux can increase by a factor of four within 30 seconds, and they are also detectable at radio frequencies. They reflect the spin of a magnetic white dwarf, which we find to be slowing down on a 10 7 -year timescale. The spin-down power is an order of magnitude larger than that seen in electromagnetic radiation, which, together with an absence of obvious signs of accretion, suggests that AR Sco is primarily spin-powered. Although the pulsations are driven by the white dwarf's spin, they mainly originate from the cool star. AR Sco's broadband spectrum is characteristic of synchrotron radiation, requiring relativistic electrons. These must either originate from near the white dwarf or be generated in situ at the M star through direct interaction with the white dwarf's magnetosphere.

Interpersonal aggression victimization within casual sexual relationships and experiences.

PubMed

Klipfel, Katherine M; Claxton, Shannon E; van Dulmen, Manfred H M

2014-02-01

The frequent occurrence of aggression within committed romantic relationships is well documented. However, little is known about experiences of interpersonal aggression within casual sexual relationships and experiences. This study aimed to describe the occurrence of emotional, physical, and sexual aggression victimization within committed romantic relationships, casual dating relationships, friends-with-benefit relationships, booty-calls, and one-night stands. College students (N = 172) provided data regarding the lifetime occurrence of emotional, physical, and sexual aggression across different forms of casual sexual relationships and experiences (friends-with-benefits, booty-call, casual dating, one-night stands, committed relationships). Emotional, physical, and sexual subtypes of aggression were reported across all casual sexual relationships and experiences. While a higher percentage of individuals who had been involved in committed relationships reported experiencing at least one form of aggression (approximately 69%), prevalence of at least one form of aggression ranged from approximately 31% to 36% for the various casual sexual relationships/experiences. Across relationships/experiences, emotional and sexual aggression were more common than physical aggression. The findings from this study indicate that emotional, physical, and sexual aggression occur across types of relationships and experiences. Thus, the current study underscores the importance of considering casual dating, friends-with-benefits, booty-calls, and one-night stands when assessing interpersonal aggression.

Quartz 9-inch size mask blanks for ArF PSM (Phase Shift Mask)

NASA Astrophysics Data System (ADS)

Harashima, Noriyuki; Isozaki, Tatsuya; Kawanishi, Arata; Kanai, Shuichiro; Kageyama, Kagehiro; Iso, Hiroyuki; Chishima, Tatsuya

2017-07-01

Semiconductor technology nodes are steadily miniaturizing. On the other hand, various efforts have been made to reduce costs, mass production lines have shifted from 200 mmφ of Si wafer to 300 mmφ, and technology development of Si wafer 450 mmφ is also in progress. As a photomask, 6-inch size binary Cr mask has been used for many years, but in recent years, the use of 9-inch binary Cr masks for Proximity Lithography Process in automotive applications, MEMS, packages, etc. has increased, and cost reduction has been taken. Since the miniaturization will progress in the above applications in the future, products corresponding to miniaturization are also desired in 9-inch photomasks. The high grade Cr - binary mask blanks used in proximity exposure process, there is a prospect of being able to use it by ULVAC COATING CORPORATION's tireless research. As further demands for miniaturization, KrF and ArF Lithography Process, which are used for steppers and scanners , there are also a demand for 9-inch size Mask Blanks. In ULVAC COATING CORPORATION, we developed a 9 - inch size KrF PSM mask Blanks prototype in 2016 and proposed a new high grade 9 - inch photomask. This time, we have further investigated and developed 9-inch size ArF PSM Mask Blanks corresponding to ArF Lithography Process, so we report it.

The 1982 ultraviolet eclipse of the symbiotic binary AR Pav

NASA Technical Reports Server (NTRS)

Hutchings, J. B.; Cowley, A. P.; Ake, T. B.; Imhoff, C. L.

1983-01-01

Observations with the International Ultraviolet Explorer (IUE) of the symbiotic binary AR Pav through its 1982 eclipse show that the hot star is not eclipsed. The hot star is associated with an extended region of continuum emission which is partially eclipsed. The eclipsed radiation is hotter near to its center, with a maximum temperature of about 9000 K. The uneclipsed flux is hotter than this. UV emission lines are not measurably eclipsed and presumably arise in a much larger region than the continuum. These data provide new constraints on models of the system but also are apparently in contradiction to those based on ground-based data.

Four functions for four relationships: consensus definitions of university students.

PubMed

Jonason, Peter K

2013-11-01

In this study (N = 192; 124 women, 68 men), consensus definitions of one-night stands, booty-call relationships, friends-with-benefits, and serious romantic relationships were fashioned using a sample of university students. Participants provided a Likert and forced-choice assessment of how each relationship was characterized by the functions of sexual gratification, trial run, placeholder, and socioemotional support. Serious romantic relationships were primarily used to gain socioemotional support. Friends-with-benefits relationships were motivated by seeking a placeholder until someone better came along and as a trial run for a more serious relationship. Booty-call relationships and one-night stands were motivated primarily by a desire for sexual gratification. Men ascribed a greater range of reasons to engage in sexual relationships than women did and the more short-term the relationship was in nature, the greater the emergence of sex differences in ascribed functions.

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.

PubMed

Hsu, Cheng-Lung; Liu, Jai-Shin; Wu, Po-Long; Guan, Hong-Hsiang; Chen, Yuh-Ling; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Yeh, Shauh-Der; Ma, Wen-Lung; Chen, Chung-Jung; Wu, Wen-Guey; Chang, Chawnshang

2014-12-01

Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

AR Sco: the first white dwarf pulsar?

NASA Astrophysics Data System (ADS)

Gaensicke, Boris

2015-10-01

AR Sco was mis-classified in 1971 as a pulsating delta-Scuti star, and has received little attention until now. In May this year, we became aware of the truly unique nature of this object: besides a two-magnitude modulation on the 3.56h orbital period, we detected a coherent 2min variability from the optical into the radio, and a spectacular infrared excess across the WISE bands. Our optical spectroscopy reveals a late-type companion star, clearly identifying AR Sco as a compact binary. While most of its observational characteristics are reminiscent of neutron star or black hole binaries, the 2min modulation is archetypical of the spin period of a strongly magnetic white dwarf. We believe that AR Sco is the first white dwarf radio pulsar, where the combination of a large field and rapid rotation results in the acceleration of relativisitic particles that blast the inner hemisphere of the M-dwarf companion, akin to the well-known milli-second pulsars. The ultimate proof of our hypothesis relies on the unambiguous identification of the white dwarf, which will be achieved through the detection of Zeeman-split Ly alpha absorption in the requested COS/G140L observations.

Calculating the surface tension of binary solutions of simple fluids of comparable size

NASA Astrophysics Data System (ADS)

Zaitseva, E. S.; Tovbin, Yu. K.

2017-11-01

A molecular theory based on the lattice gas model (LGM) is used to calculate the surface tension of one- and two-component planar vapor-liquid interfaces of simple fluids. Interaction between nearest neighbors is considered in the calculations. LGM is applied as a tool of interpolation: the parameters of the model are corrected using experimental surface tension data. It is found that the average accuracy of describing the surface tension of pure substances (Ar, N2, O2, CH4) and their mixtures (Ar-O2, Ar-N2, Ar-CH4, N2-CH4) does not exceed 2%.

Multiwavelength observations of magnetic fields and related activity on XI Bootis A

NASA Technical Reports Server (NTRS)

Saar, Steven H.; Huovelin, J.; Linsky, Jeffrey L.; Giampapa, Mark S.; Jordan, Carole

1988-01-01

Preliminary results of coordinated observations of magnetic fields and related activity on the active dwarf, Xi Boo A, are presented. Combining the magnetic fluxes with the linear polarization data, a simple map of the stellar active regions is constructed.

An Intense Polarized Radio Flare from AR Lac

NASA Astrophysics Data System (ADS)

Mutel, R. L.; Neff, J. E.; Bookbinder, J.; Pagano, I.

1992-12-01

We have detected an intense, highly circularly polarized radio flare from the close binary system AR Lacertae during a 4 day multi-wavelength observing campaign in 1991 December. The flare lasted more than 6 hours and was preceded by a strong CIV flare one day earlier. The peak circular polarization was 70%, 38%,and 39% RCP at 1.4, 4.9, and 8.4 GHz respectively, with ~ 15% LCP at 15 and 22 GHZ. The high degree of circular polarization over such a large time scale and frequency range is highly unusual compared with previously observed radio flares from RS CVn binaries. Given these unusual characteristics, it is difficult to interpret the radiation mechanism either as a result of gyrosynchrotron emission or a coherent process such as an electron cyclotron maser.

What we learn from eclipsing binaries in the ultraviolet

NASA Technical Reports Server (NTRS)

Guinan, Edward F.

1990-01-01

Recent results on stars and stellar physics from IUE (International Ultraviolet Explorer) observations of eclipsing binaries are discussed. Several case studies are presented, including V 444 Cyg, Aur stars, V 471 Tau and AR Lac. Topics include stellar winds and mass loss, stellar atmospheres, stellar dynamos, and surface activity. Studies of binary star dynamics and evolution are discussed. The progress made with IUE in understanding the complex dynamical and evolutionary processes taking place in W UMa-type binaries and Algol systems is highlighted. The initial results of intensive studies of the W UMa star VW Cep and three representative Algol-type binaries (in different stages of evolution) focused on gas flows and accretion, are included. The future prospects of eclipsing binary research are explored. Remaining problems are surveyed and the next challenges are presented. The roles that eclipsing binaries could play in studies of stellar evolution, cluster dynamics, galactic structure, mass luminosity relations for extra galactic systems, cosmology, and even possible detection of extra solar system planets using eclipsing binaries are discussed.

Orbital period studies of the two contact binaries TZ Bootis and Y Sextantis

NASA Astrophysics Data System (ADS)

Qian, S.; Liu, Q.

2000-03-01

The physical properties of the two A-type contact binaries TZ Boo and Y Sex are nearly the same. In the present paper, many of their published times of light minima are collected and the changes in their orbital periods are analyzed. It is indicated that the orbital period of TZ Boo shows several alternating jumps while it undergoes a secular decrease of -11.8x10-8 days/year. Several random jumps superposed on a secular decrease (-5.5x10-8 days/year) are also found in the period of Y Sex. The secular decrease is usually interpreted as mass transfer from the more to the less massive components, or mass and angular momentum loss (AML) from the systems. According to the AML theory, on the contact stage, the orbital AML is mainly caused by the mass transfer from the less to the more massive component and the mass ratio decreasing and orbital period gradually increasing are the corresponding results. The extremely low mass ratio and orbital angular momentum of the two systems show that they are evolved via AML and the present secular decrease in the periods may suggest that the magnetic activity in the two systems are very strong. The relation between the changes of the orbital periods and the magnetic activity in the two systems are discussed. We think that the interplay between the variable AML and variable magnetic coupling can explain both the jumps and secular decrease in the orbital periods of the two systems. Table~2 and Table~4 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strabg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html

Learning Optimized Local Difference Binaries for Scalable Augmented Reality on Mobile Devices.

PubMed

Xin Yang; Kwang-Ting Cheng

2014-06-01

The efficiency, robustness and distinctiveness of a feature descriptor are critical to the user experience and scalability of a mobile augmented reality (AR) system. However, existing descriptors are either too computationally expensive to achieve real-time performance on a mobile device such as a smartphone or tablet, or not sufficiently robust and distinctive to identify correct matches from a large database. As a result, current mobile AR systems still only have limited capabilities, which greatly restrict their deployment in practice. In this paper, we propose a highly efficient, robust and distinctive binary descriptor, called Learning-based Local Difference Binary (LLDB). LLDB directly computes a binary string for an image patch using simple intensity and gradient difference tests on pairwise grid cells within the patch. To select an optimized set of grid cell pairs, we densely sample grid cells from an image patch and then leverage a modified AdaBoost algorithm to automatically extract a small set of critical ones with the goal of maximizing the Hamming distance between mismatches while minimizing it between matches. Experimental results demonstrate that LLDB is extremely fast to compute and to match against a large database due to its high robustness and distinctiveness. Compared to the state-of-the-art binary descriptors, primarily designed for speed, LLDB has similar efficiency for descriptor construction, while achieving a greater accuracy and faster matching speed when matching over a large database with 2.3M descriptors on mobile devices.

AR Sco observing campaign

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2016-08-01

Dr. Thomas Marsh (University of Warwick) and colleagues have requested AAVSO coverage of the intriguing binary AR Sco in support of upcoming Newton-XMM observations scheduled for 2016 September 10 15:41 - September 11 02:26 UT. This fascinating binary system is the subject of an exciting paper in the July 2016 issue of Nature (Marsh et al., 2016Natur.537..374M; pre-print version at arXiv (http://arxiv.org/abs/1607.08265). Marsh writes of their research on AR Sco: "...it was down to [the amateurs [who are co-authors] on the paper that we got onto it in the first place. Coverage immediately before, after and (especially) during [the XMM observations] would be great. The most challenging aspect is the time resolution: ideally one wants a cadence < 29 seconds because of the strong harmonic of the basic 2 minute period, and the faster the better. Observers should use whatever filter (including clear/white light) is needed to allow them to match this constraint. Accurate timing is also essential - the centres of the exposures need to be known to better than ± 2 seconds, and preferably better." A page of materials on AR Sco related to the Nature paper may be found at http://deneb.astro.warwick.ac.uk/phsaap/arsco-info/ . Item #9 on that page is a YouTube video of a fascinating movie Dr. Marsh made of AR Sco from their data (https://www.youtube.com/watch?v=QJGAv2jCF4s&feature=youtu.be). Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

Selective dry etching of III-V nitrides in Cl{sub 2}/Ar, CH{sub 4}/H{sub 2}/Ar, ICi/Ar, and IBr/Ar

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

Vartuli, C.B.; Pearton, S.J.; MacKenzie, J.D.

1996-10-01

The selectivity for etching the binary (GaN, AlN, and InN) and ternary nitrides (InGaN and InAlN) relative to each other in Cl{sub 2}/Ar, CH{sub 4}/H{sub 2}/Ar, ICl/Ar, or IBr/Ar electron cyclotron resonance (ECR) plasmas, and Cl{sub 2}/Ar or CH{sub 4}/H{sub 2}/Ar reactive ion (RIE) plasmas was investigated. Cl-based etches appear to be the best choice for maximizing the selectivity of GaN over the other nitrides. GaN/AlN and GaN/InGaN etch rate ratios of {approximately} 10 were achieved at low RF power in Cl{sub 2}/Ar under ECR and RIE conditions, respectively. GaN/InN selectivity of 10 was found in ICl under ECR conditions.more » A relatively high selectivity (> 6) of InN/GaN was achieved in CH{sub 4}/H{sub 2}/Ar under ECR conditions at low RF powers (50 W). Since the high bond strengths of the nitrides require either high ion energies or densities to achieve practical etch rates it is difficult to achieve high selectivities.« less

Individual and combined in vitro (anti)androgenic effects of certain food additives and cosmetic preservatives.

PubMed

Pop, Anca; Drugan, Tudor; Gutleb, Arno C; Lupu, Diana; Cherfan, Julien; Loghin, Felicia; Kiss, Béla

2016-04-01

The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti-androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha-dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transform-Based Wideband Array Processing

DTIC Science & Technology

1992-01-31

Breusch and Pagan [2], it is possible to test which model, M,€, 0 AR or random coefficient, will better fit typical array data. Li The test indicates that...bearing estimation problems," Proc. IEEE, vol. 70, no. 9, pp. 1018-1028, 1982. (2] T. S. Breusch and A. R. Pagan , "A simple test for het...cor- relations do not obey an AR relationship across the array; relations in the observations. Through the use of a binary hypothesis test , it is

One-step argon/nitrogen binary plasma jet irradiation of Li4Ti5O12 for stable high-rate lithium ion battery anodes

NASA Astrophysics Data System (ADS)

Lan, Chun-Kai; Chuang, Shang-I.; Bao, Qi; Liao, Yen-Ting; Duh, Jenq-Gong

2015-02-01

Atmospheric pressure Ar/N2 binary plasma jet irradiation has been introduced into the manufacturing process of lithium ions batteries as a facile, green and scalable post-fabrication treatment approach, which enhanced significantly the high-rate anode performance of lithium titanate (Li4Ti5O12). Main emission lines in Ar/N2 plasma measured by optical emission spectroscopy reveal that the dominant excited high-energy species in Ar/N2 plasma are N2*, N2+, N∗ and Ar∗. Sufficient oxygen vacancies have been evidenced by high resolution X-ray photoelectron spectroscopy analysis and Raman spectra. Nitrogen doping has been achieved simultaneously by the surface reaction between pristine Li4Ti5O12 particles and chemically reactive plasma species such as N∗ and N2+. The variety of Li4Ti5O12 particles on the surface of electrodes after different plasma processing time has been examined by grazing incident X-Ray diffraction. Electrochemical impedance spectra (EIS) confirm that the Ar/N2 atmospheric plasma treatment facilitates Li+ ions diffusion and reduces the internal charge-transfer resistance. The as-prepared Li4Ti5O12 anodes exhibit a superior capacity (132 mAh g-1) and excellent stability with almost no capacity decay over 100 cycles under a high C rate (10C).

Underwater Cycle Ergometry: Power Requirements With and Without Diver Thermal Dress

DTIC Science & Technology

2009-01-01

cycle ergometers were built at NEDU as successors to the waterproofed Collins Pedal Mate ergometers that are no longer available. A pedal shaft drives...8217 feet to the pedals. In contrast to the large foot cups and neoprene booties used at NEDU, regular bicycle pedals with toe straps2 over canvas shoes

The Small Schools Movement: Implications for Health Education

ERIC Educational Resources Information Center

Cleary, Michael; English, Gary

2005-01-01

Approximately 70% of American high schools enroll 1000 or more students each, while almost one half of high schools enroll more than 1500 students each. A growing booty of evidence, however, is showing that small schools, especially small secondary schools, result in positive benefits for students, families, and communities that go beyond letter…

BRAZILIAN BOOTY RETINOPATHY: PURTSCHER-LIKE RETINOPATHY WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH PMMA INJECTION INTO BUTTOCKS.

PubMed

Khatibi, Azadeh

2018-01-01

To report a case of Purtscher-like retinopathy with paracentral acute middle maculopathy preceded by febrile illness after filler injection into the buttock muscles bilaterally for cosmesis to achieve a "Brazilian booty." Retrospective case report. A 35-year-old female presented with febrile illness and then decreased vision after repeat polymethyl methacrylate injections into her buttock muscles in Mexico. Examination was significant for retinal whitening, especially in the perifoveal areas, and intraretinal hemorrhages. Optical coherence tomography and fluorescein angiography imaging were consistent with small-vessel ischemic disease in the retina and choroid. Once systemic infection was ruled out, patient was treated with high-dose intravenous and then oral steroids. Vision recovery was good, with retinal atrophy on optical coherence tomography in the previous areas of retinal whitening. A Purtscher-like retinopathy with paracentral acute middle maculopathy and loss of vision may occur after filler injection below the neck, not just the face. This is the first report of vision loss caused by filler injected outside the face.

Long-term magnetic activity in close binary systems. I. Patterns of color variations

NASA Astrophysics Data System (ADS)

Messina, S.

2008-03-01

Aims:This is the first of a series of papers in which we present the results of a long-term photometric monitoring project carried out at Catania Astrophysical Observatory aimed at studying magnetic activity in late-type components of close binary systems, its dependence on global stellar parameters, and its evolution on different time scales from days to years. In this first paper, we present the complete observation dataset and new results of an investigation into the origin of brightness and color variations observed in the well-known magnetically active close binary stars: AR Psc, VY Ari, UX Ari, V711 Tau, EI Eri, V1149 Ori, DH Leo, HU Vir, RS CVn, V775 Her, AR Lac, SZ Psc, II Peg and BY Dra Methods: About 38 000 high-precision photoelectric nightly observations in the U, B and V filters are analysed. Correlation and regression analyses of the V magnitude vs. U-B and B-V color variations are carried out and a comparison with model variations for a grid of active region temperature and filling factor values is also performed. Results: We find the existence of two different patterns of color variation. Eight stars in our sample: BY Dra, VY Ari, V775 Her, II Peg, V1149 Ori, HU Vir, EI Eri and DH Leo become redder when they become fainter, as is expected from the presence of active regions consisting of cool spots. The other six stars show the opposite behaviour, i.e. they become bluer when they become fainter. For V711 Tau this behaviour could be explained by the increased relative U- and B-flux contribution by the earlier-type component of the binary system when the cooler component becomes fainter. On the other hand, for AR Psc, UX Ari, RS CVn, SZ Psc and AR Lac the existence of hot photospheric faculae must be invoked. We also found that in single-lined and double-lined binary stars in which the fainter component is inactive or much less active the V magnitude is correlated to B-V and U-B color variations in more than 60% of observation seasons. The correlation is found in less than 40% of observation seasons when the fainter component has a non-negligible level of activity and/or hot faculae are present but they are either spatially or temporally uncorrelated to spots. I dedicate this paper to the memory of the P.I. of this project, Prof. Marcello Rodonò, who suddenly passed away on October 23, 2005. To him my sincere estimation and deepest gratitude. Based on observations collected at INAF-Catania Astrophysical Observatory, Italy.

CASTLE BRAVO: Fifty Years of Legend and Lore. A Guide to Off-Site Radiation Exposures

DTIC Science & Technology

2013-01-31

Radiological Surveys ............................................................... 90 4.2 The HASL Fixed Instrument Network...87 Figure 4-1. The radiation survey party comes ashore on Rongelap Island, 20 April 1954 .......... 89 Figure 4-2. The task... survey party from the USS Nicholas (DDE-449) lands at Rongelap Island. Note anticontamination booties worn over shoes. 9 March 1954

[Theft with subsequent murder].

PubMed

Rothschild, M A; Schneider, V

1990-01-01

We studied 39 cases from autopsies made between 1978 and 1988 in the Institut für Rechtsmedizin der Freien Universität Berlin and the Landesinstitut für gerichtliche und soziale Medizin Berlin in which the public prosecutor's office had investigated about robbery in coincidence with killing. The average age of the victims was 75 years, the average age of the perpetrators was 21 years. One third of the victims died because of bronchopneumonia. 5 victims only showed slight injuries, the autopsy showed no definite cause of death, but we found severe signs of illness of the organs resp. of the heart. In these cases we diagnosed a "psycho-physiological cause of death". One third of the victims had a severe stenosis of the coronary system and one third showed cardiac hypertrophy of over 450 g. Head and face had been the favorite target of the perpetrators. Most localisations of crime had been the apartments of the victims and the booty often was less than DM 100,-. 75% of the perpetrators had been previously convicted. In the cases with "psycho-physiological" cause of death the court condemned the perpetrators only because of booty but never because of killing.

Spins of complex fragments in binary reactions within a dinuclear system model

NASA Astrophysics Data System (ADS)

Paşca, H.; Kalandarov, Sh. A.; Adamian, G. G.; Antonenko, N. V.

2017-10-01

The average angular momenta and widths of the spin distributions of reaction products are calculated within the dinuclear system model. The thermal excitation of rotational bearing modes is considered in the dinuclear system. The calculated fragment spins (γ multiplicities) and their variances in the reactions 20Ne (166 MeV) + 63Cu, 40Ar (280 MeV) + 58Ni, 20Ne (175 MeV) + natAg, 40Ar (237 MeV) + 89Y, 40Ar (288 and 340 MeV) + Ag,109107, and 16O (100 MeV) + 58Ni are compared with the available experimental data. The influence of the entrance channel charge (mass) asymmetry and bombarding energy on the characteristics of spin distribution is studied.

Absolute dimensions of eclipsing binaries. XXVI.. Setting a new standard: Masses, radii, and abundances for the F-type systems AD Bootis VZ Hydrae, and WZ Ophiuchi

NASA Astrophysics Data System (ADS)

Clausen, J. V.; Torres, G.; Bruntt, H.; Andersen, J.; Nordström, B.; Stefanik, R. P.; Latham, D. W.; Southworth, J.

2008-09-01

Context: Accurate mass, radius, and abundance determinations from binaries provide important information on stellar evolution, fundamental to central fields in modern astrophysics and cosmology. Aims: We aim to determine absolute dimensions and abundances for the three F-type main-sequence detached eclipsing binaries AD Boo, VZ Hya, and WZ Oph and to perform a detailed comparison with results from recent stellar evolutionary models. Methods: uvby light curves and uvbyβ standard photometry were obtained with the Strömgren Automatic Telescope at ESO, La Silla, radial velocity observations at CfA facilities, and supplementary high-resolution spectra with ESO's FEROS spectrograph. State-of-the-art methods were applied for the analyses: the EBOP and Wilson-Devinney binary models, two-dimensional cross-correlation and disentangling, and the VWA abundance analysis tool. Results: Masses and radii that are precise to 0.5-0.7% and 0.4-0.9%, respectively, have been established for the components, which span the ranges of 1.1 to 1.4 M⊙ and 1.1 to 1.6 R⊙. The [Fe/H] abundances are from -0.27 to +0.10, with uncertainties between 0.07 and 0.15 dex. We find indications of a slight α-element overabundance of [α/Fe] ˜ + 0.1 for WZ Oph. The secondary component of AD Boo and both components of WZ Oph appear to be slightly active. Yale-Yonsai and Victoria-Regina evolutionary models fit the components of AD Boo and VZ Hya almost equally well, assuming coeval formation, at ages of about 1.75/1.50 Gyr (AD Boo) and 1.25/1.00 Gyr (VZ Hya). BaSTI models, however, predict somewhat different ages for the primary and secondary components. For WZ Oph, the models from all three grids are significantly hotter than observed. A low He content, decreased envelope convection coupled with surface activity, and/or higher interstellar absorption would remove the discrepancy, but its cause has not been definitively identified. Conclusions: We have demonstrated the power of testing and comparing recent stellar evolutionary models using eclipsing binaries, provided their abundances are known. The strongest limitations and challenges are set by T_eff and interstellar absorption determinations, and by their effects on and correlation with abundance results. Based on observations carried out at the Strömgren Automatic Telescope (SAT) and the 1.5 m and 2.2 m telescopes at ESO, La Silla, Chile (62.L-0284, 63.H-0080, 71.D-0554); the 1.5 m Wyeth reflector at the Oak Ridge Observatory, Harvard, Massachusetts, USA; the 1.5-m Tillinghast reflector and the Multiple Mirror Telescope at the F. L. Whipple Observatory, Mt. Hopkins, Arizona.

Binary asteroid orbit evolution due to primary shape deformation

NASA Astrophysics Data System (ADS)

Hirabayashi, Masatoshi; Jacobson, Seth A.; Davis, Alex

2017-10-01

About a sixth of all small asteroid systems are binary [Margot et al., Science, 2002]. Many binary asteroids consist of an elongated synchronous secondary body orbiting a fast-rotating spheroidal primary body with ridges on its equator. The primary in such systems has experienced a long-term spin-up due to the YORP effect [Vokrouhlick'y et al., Asteroid IV, 2015]. This spin-up process can make the primary reach its spin barrier inducing shape deformation processes that ease the structural condition for failure inside the primary [e.g., Holsapple, Icarus, 2010]. Earlier works have shown that structural heterogeneities in the primary such as the shape and density distribution induce asymmetric deformation [Sánchez and Scheeres, Icarus, 2016]. Here, we investigate how asymmetric shape deformation in the primary affects the mutual motion of a binary system. We use a dynamics model for an irregularly shaped binary system that accounts for possible deformation of the primary [Hirabayashi et al., LPSC, 2017]. In this model, we consider asymmetric deformation that occurs based on structural failure in the primary and thus it modifies the location of the center of mass of the system. Using 1999 KW4 as an example, we study a hypothetical case in which the primary is initially identical to the current shape [Ostro et al., Science, 2006] with an aspect ratio (AR) of 0.83 and then suddenly changes its shape to an AR of 0.76. The results show that the asymmetric deformation process and the shift of the center of mass excite the eccentricity of the mutual orbit. Considering that the original mutual orbit has an eccentricity of 0.0004, after the primary shape change the eccentricity reaches values up to 0.15. Also, since the gravity field is modified after deformation, the secondary’s spin is desynchronized from the mutual orbit. Since synchronicity is a requirement for the binary YORP (BYORP) effect, which modifies the semi-major axis of binary asteroids, a primary shape change temporarily pauses the BYORP effect, in effect lengthening the effective BYORP timescale.

Dynamic secondary ion mass spectroscopy of Au nanoparticles on Si wafer using Bi3+ as primary ion coupled with surface etching by Ar cluster ion beam: The effect of etching conditions on surface structure

NASA Astrophysics Data System (ADS)

Park, Eun Ji; Choi, Chang Min; Kim, Il Hee; Kim, Jung-Hwan; Lee, Gaehang; Jin, Jong Sung; Ganteför, Gerd; Kim, Young Dok; Choi, Myoung Choul

2018-01-01

Wet-chemically synthesized Au nanoparticles were deposited on Si wafer surfaces, and the secondary ions mass spectra (SIMS) from these samples were collected using Bi3+ with an energy of 30 keV as the primary ions. In the SIMS, Au cluster cations with a well-known, even-odd alteration pattern in the signal intensity were observed. We also performed depth profile SIMS analyses, i.e., etching the surface using an Ar gas cluster ion beam (GCIB), and a subsequent Bi3+ SIMS analysis was repetitively performed. Here, two different etching conditions (Ar1600 clusters of 10 keV energy or Ar1000 of 2.5 keV denoted as "harsh" or "soft" etching conditions, respectively) were used. Etching under harsh conditions induced emission of the Au-Si binary cluster cations in the SIMS spectra of the Bi3+ primary ions. The formation of binary cluster cations can be induced by either fragmentation of Au nanoparticles or alloying of Au and Si, increasing Au-Si coordination on the sample surface during harsh GCIB etching. Alternatively, use of the soft GCIB etching conditions resulted in exclusive emission of pure Au cluster cations with nearly no Au-Si cluster cation formation. Depth profile analyses of the Bi3+ SIMS combined with soft GCIB etching can be useful for studying the chemical environments of atoms at the surface without altering the original interface structure during etching.

Cumulative Effects of In Utero Administration of Mixtures of Reproductive Toxicants that Disrupt Common Target Tissues via Diverse Mechanisms of Toxicity

PubMed Central

Rider, Cynthia V.; Furr, Johnathan R.; Wilson, Vickie S.; Gray, L. Earl

2010-01-01

Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act required the US Environmental Protection Agency to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures of chemicals to elucidate mechanisms of joint action at the systemic level with the end goal of providing a framework for assessing the cumulative effects of reproductive toxicants. Previous mixture studies conducted with antiandrogenic chemicals are reviewed briefly and two new studies are described in detail. In all binary mixture studies, rats were dosed during pregnancy with chemicals, singly or in pairs at dosage levels equivalent to approximately one half of the ED50 for hypospadias or epididymal agenesis. The binary mixtures included: androgen receptor (AR) antagonists (vinclozolin plus procymidone), phthalate esters (DBP plus BBP and DEHP plus DBP), a phthalate ester plus an AR antagonist (DBP plus procymidone), a mixed mechanism androgen signaling disruptor (linuron) plus BBP, and two chemicals which disrupt epididymal differentiation through entirely different toxicity pathways: DBP (AR pathway) plus 2,3,7,8 TCDD (AhR pathway). We also conducted multi-component mixture studies combining several “antiandrogens” together. In the first study, seven chemicals (four pesticides and three phthalates) that elicit antiandrogenic effects at two different sites in the androgen signaling pathway (i.e. AR antagonist or inhibition of androgen synthesis) were combined. In the second study, three additional phthalates were added to make a ten chemical mixture. In both the binary mixture studies and the multi-component mixture studies, chemicals that targeted male reproductive tract development displayed cumulative effects that exceeded predictions based upon a response addition model and most often were in accordance with predictions based upon dose addition models. In summary, our results indicate that compounds that act by disparate mechanisms of toxicity to disrupt the dynamic interactions among the interconnected signaling pathways in differentiating tissues produce cumulative dose-additive effects, regardless of the mechanism or mode of action of the individual mixture component. PMID:20487044

Development of a mobile borehole investigation software using augmented reality

NASA Astrophysics Data System (ADS)

Son, J.; Lee, S.; Oh, M.; Yun, D. E.; Kim, S.; Park, H. D.

2015-12-01

Augmented reality (AR) is one of the most developing technologies in smartphone and IT areas. While various applications have been developed using the AR, there are a few geological applications which adopt its advantages. In this study, a smartphone application to manage boreholes using AR has been developed. The application is consisted of three major modules, an AR module, a map module and a data management module. The AR module calculates the orientation of the device and displays nearby boreholes distributed in three dimensions using the orientation. This module shows the boreholes in a transparent layer on a live camera screen so the user can find and understand the overall characteristics of the underground geology. The map module displays the boreholes on a 2D map to show their distribution and the location of the user. The database module uses SQLite library which has proper characteristics for mobile platforms, and Binary XML is adopted to enable containing additional customized data. The application is able to provide underground information in an intuitive and refined forms and to decrease time and general equipment required for geological field investigations.

A study of nonflammable ArCO 2-hydrocarbon gas mixtures for limited streamer tubes

NASA Astrophysics Data System (ADS)

Cartwright, S.; Schneekloth, U.; Alpat, B.; Artemi, C.; Battiston, R.; Bilei, G.; Italiani, M.; Pauluzzi, M.; Servoli, L.; Messner, R.; Wyss, J.; Zdarko, R.; Johnson, J.

1989-04-01

The gas mixtures generally used until now in limited streamer tube detectors (Ar+C 4H 10 or Ar+CO 2+C 5H 12) are very flammable when leaked into air. The safety issues are therefore very relevant for large-volume underground experiments. We have found a set of completely safe (i.e. nonflammable) ternary mixtures of the kind Ar + hydrocarbon + CO 2 containing less than ˜ 5% of Ar and less than ˜ 10% of hydrocarbon. We tested C 4H 10, C 5H 12 and C 6H 14 as quenching agents. The main characteristics of the various mixtures have been measured: singles (untriggered) counting rate versus high voltage and with different dead times, and average charge. The stability of these mixtures is good, and their spurious streamer activity is compared with the standard binary or ternary mixture. We studied in particular the combination Ar(2.5%) + C 4H 10(9.5%) + CO 2(88%). All the data suggest that this or a similar gas mixture can successfully replace standard flammable mixtures both in tracking devices and hadron calorimeters.

Can Russia Reform? Economic, Political, and Military Perspectives

DTIC Science & Technology

2012-06-01

formation of a diversified economic model , it did not halt the growth of the gap between Russia and the developed world either. The result will be...years. The pure model was a unitary state economic governance scheme where Tsars, (principals) unable to micro-plan and command production...subsistence, and dividing the booty arbitrarily among themselves. TSARIST STATE ECONOMIC MANAGEMENT REFORM The core model served its purpose and was

Transverse optic-like modes in binary liquids

NASA Astrophysics Data System (ADS)

Bryk, Taras; Mryglod, Ihor

1999-10-01

Generalized collective mode approach and MD simulations are applied for the study of transverse dynamics in a LJ fluid KrAr and a liquid alloy Mg 70Zn 30. The optic-like excitations, caused by the mass-concentration fluctuations, are found in both mixtures considered. Mode contributions into the total spectral function are investigated.

Use of Relativistic Effective Core Potentials in the Calculation of Electron-Impact Ionization Cross Sections

NASA Technical Reports Server (NTRS)

Huo, Winifred M.; Kim, Yong-Ki

1999-01-01

Based on the Binary-Encounter-Bethe (BEB) model, the advantage of using relativistic effective core potentials (RECP) in the calculation of total ionization cross sections of heavy atoms or molecules containing heavy atoms is discussed. Numerical examples for Ar, Kr, Xe, and WF6 are presented.

Period changes of the sample of eclipsing binaries with active chromospheres

NASA Astrophysics Data System (ADS)

Jableka, D.; Zola, S.; Zakrzewski, B.; Szymanski, T.; Kuzmicz, A.; de Villiers, S. N.; Zejda, M.; Koziel-Wierzbowska, D.

2012-11-01

In this work we present results derived from analysis of the O-C behaviour of ten eclipsing binary systems: AR Lac, CG Cyg, HP Aur, MM Her, RS CVn, RT And, SV Cam, V471 Tau, WW Dra and CF Tuc. It was proved on the basis of moments of minima compiled from the literature and new ones determined from recent observations, that these binaries show long term (19-91 years) modulations of their orbital periods, clearly visible in their O-C diagrams. Two possible explanations for this effect are considered: (1) the light-travel time effect due to the presence of a third body orbiting the eclipsing systems; (2) the Applegate mechanism predicting period modulation by changes in the distribution of angular momentum as a star goes through its activity cycles. It was found that in the case of four systems the existence of a third star, orbiting the binary, is a more plausible explanation of observations.

TIME-VARIABLE ALUMINUM ABSORPTION IN THE POLAR AR URSAE MAJORIS, AND AN UPDATED ESTIMATE FOR THE MASS OF THE WHITE DWARF

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

Bai, Yu; Justham, Stephen; Liu, JiFeng

2016-09-01

We present spectra of the extreme polar AR Ursae Majoris (AR UMa), which display a clear Al i absorption doublet, alongside spectra taken less than a year earlier in which that feature is not present. Re-examination of earlier SDSS spectra indicates that the Al i absorption doublet was also present ≈8 years before our first non-detection. We conclude that this absorbing material is unlikely to be on the surface of either the white dwarf (WD) or the donor star. We suggest that this Al i absorption feature arises in circumstellar material, perhaps produced by the evaporation of asteroids as theymore » approach the hot WD. The presence of any remaining reservoir of rocky material in AR UMa might help to constrain the prior evolution of this unusual binary system. We also apply spectral decomposition to find the stellar parameters of the M dwarf companion, and attempt to dynamically measure the mass of the WD in AR UMa by considering both the radial velocity curves of the H {sub β} emission line and the Na i absorption line. Thereby we infer a mass range for the WD in AR UMa of 0.91 M {sub ⊙} < M {sub WD} < 1.24 M {sub ⊙}.« less

Time-variable Aluminum Absorption in the Polar AR Ursae Majoris, and an Updated Estimate for the Mass of the White Dwarf

NASA Astrophysics Data System (ADS)

Bai, Yu; Justham, Stephen; Liu, JiFeng; Guo, JinCheng; Gao, Qing; Gong, Hang

2016-09-01

We present spectra of the extreme polar AR Ursae Majoris (AR UMa), which display a clear Al I absorption doublet, alongside spectra taken less than a year earlier in which that feature is not present. Re-examination of earlier SDSS spectra indicates that the Al I absorption doublet was also present ≈8 years before our first non-detection. We conclude that this absorbing material is unlikely to be on the surface of either the white dwarf (WD) or the donor star. We suggest that this Al I absorption feature arises in circumstellar material, perhaps produced by the evaporation of asteroids as they approach the hot WD. The presence of any remaining reservoir of rocky material in AR UMa might help to constrain the prior evolution of this unusual binary system. We also apply spectral decomposition to find the stellar parameters of the M dwarf companion, and attempt to dynamically measure the mass of the WD in AR UMa by considering both the radial velocity curves of the H β emission line and the Na I absorption line. Thereby we infer a mass range for the WD in AR UMa of 0.91 M ⊙ < M WD < 1.24 M ⊙.

Assessment of combined antiandrogenic effects of binary parabens mixtures in a yeast-based reporter assay.

PubMed

Ma, Dehua; Chen, Lujun; Zhu, Xiaobiao; Li, Feifei; Liu, Cong; Liu, Rui

2014-05-01

To date, toxicological studies of endocrine disrupting chemicals (EDCs) have typically focused on single chemical exposures and associated effects. However, exposure to EDCs mixtures in the environment is common. Antiandrogens represent a group of EDCs, which draw increasing attention due to their resultant demasculinization and sexual disruption of aquatic organisms. Although there are a number of in vivo and in vitro studies investigating the combined effects of antiandrogen mixtures, these studies are mainly on selected model compounds such as flutamide, procymidone, and vinclozolin. The aim of the present study is to investigate the combined antiandrogenic effects of parabens, which are widely used antiandrogens in industrial and domestic commodities. A yeast-based human androgen receptor (hAR) assay (YAS) was applied to assess the antiandrogenic activities of n-propylparaben (nPrP), iso-propylparaben (iPrP), methylparaben (MeP), and 4-n-pentylphenol (PeP), as well as the binary mixtures of nPrP with each of the other three antiandrogens. All of the four compounds could exhibit antiandrogenic activity via the hAR. A linear interaction model was applied to quantitatively analyze the interaction between nPrP and each of the other three antiandrogens. The isoboles method was modified to show the variation of combined effects as the concentrations of mixed antiandrogens were changed. Graphs were constructed to show isoeffective curves of three binary mixtures based on the fitted linear interaction model and to evaluate the interaction of the mixed antiandrogens (synergism or antagonism). The combined effect of equimolar combinations of the three mixtures was also considered with the nonlinear isoboles method. The main effect parameters and interaction effect parameters in the linear interaction models of the three mixtures were different from zero. The results showed that any two antiandrogens in their binary mixtures tended to exert equal antiandrogenic activity in the linear concentration ranges. The antiandrogenicity of the binary mixture and the concentration of nPrP were fitted to a sigmoidal model if the concentrations of the other antiandrogens (iPrP, MeP, and PeP) in the mixture were lower than the AR saturation concentrations. Some concave isoboles above the additivity line appeared in all the three mixtures. There were some synergistic effects of the binary mixture of nPrP and MeP at low concentrations in the linear concentration ranges. Interesting, when the antiandrogens concentrations approached the saturation, the interaction between chemicals were antagonistic for all the three mixtures tested. When the toxicity of the three mixtures was assessed using nonlinear isoboles, only antagonism was observed for equimolar combinations of nPrP and iPrP as the concentrations were increased from the no-observed-effect-concentration (NOEC) to effective concentration of 80%. In addition, the interactions were changed from synergistic to antagonistic as effective concentrations were increased in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP. The combined effects of three binary antiandrogens mixtures in the linear ranges were successfully evaluated by curve fitting and isoboles. The combined effects of specific binary mixtures varied depending on the concentrations of the chemicals in the mixtures. At low concentrations in the linear concentration ranges, there was synergistic interaction existing in the binary mixture of nPrP and MeP. The interaction tended to be antagonistic as the antiandrogens approached saturation concentrations in mixtures of nPrP with each of the other three antiandrogens. The synergistic interaction was also found in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP, at low concentrations with another method of nonlinear isoboles. The mixture activities of binary antiandrogens had a tendency towards antagonism at high concentrations and synergism at low concentrations.

Effect of eccentricity on searches for gravitational waves from coalescing compact binaries in ground-based detectors

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

Brown, Duncan A.; Zimmerman, Peter J.

2010-01-15

Inspiralling compact binaries are expected to circularize before their gravitational-wave signals reach the sensitive frequency band of ground-based detectors. Current searches for gravitational waves from compact binaries using the LIGO and Virgo detectors therefore use circular templates to construct matched filters. Binary formation models have been proposed which suggest that some systems detectable by the LIGO-Virgo network may have non-negligible eccentricity. We investigate the ability of the restricted 3.5 post-Newtonian order TaylorF2 template bank, used by LIGO and Virgo to search for gravitational waves from compact binaries with masses M{<=}35M{sub {center_dot},} to detect binaries with nonzero eccentricity. We model themore » gravitational waves from eccentric binaries using the x-model post-Newtonian formalism proposed by Hinder et al.[I. Hinder, F. Hermann, P. Laguna, and D. Shoemaker, arXiv:0806.1037v1]. We find that small residual eccentricities (e{sub 0} < or approx. 0.05 at 40 Hz) do not significantly affect the ability of current LIGO searches to detect gravitational waves from coalescing compact binaries with total mass 2M{sub {center_dot}<}M<15M{sub {center_dot}.} For eccentricities e{sub 0} > or approx. 0.1, the loss in matched filter signal-to-noise ratio due to eccentricity can be significant and so templates which include eccentric effects will be required to perform optimal searches for such systems.« less

High-mass heterogeneous cluster formation by ion bombardment of the ternary alloy Au 7Cu 5Al 4

DOE PAGES

Zinovev, Alexander V.; King, Bruce V.; Veryovkin, Igor V.; ...

2016-02-04

The ternary alloy Au 7Cu 5Al 4 was irradiated with 0.1–10 keV Ar + and the surface composition analyzed using laser sputter neutral mass spectrometry. Ejected clusters containing up to seven atoms, with masses up to 2000 amu, were observed. By monitoring the signals from sputtered clusters, the surface composition of the alloy was seen to change with 100 eV Ar + dose, reaching equilibrium after 10 nm of the surface was eroded, in agreement with TRIDYN simulation and indicating that the changes were due to preferential sputtering of Al and Cu. Ejected gold containing clusters were found to increasemore » markedly in intensity while aluminum containing clusters decreased in intensity as a result of Ar sputtering. Such an effect was most pronounced for low energy (<1 keV) Ar + sputtering and was consistent with TRIDYN simulations of the depth profiling. As a result, the component sputter yields from the ternary alloy were consistent with previous binary alloy measurements but showed greater Cu surface concentrations than expected from TRIDYN simulations.« less

Enrichment, geo-accumulation and risk surveillance of toxic metals for different environmental compartments from Mehmood Booti dumping site, Lahore city, Pakistan.

PubMed

Aiman, Umme; Mahmood, Adeel; Waheed, Sidra; Malik, Riffat Naseem

2016-02-01

The present study was designed to probe the levels of heavy metals (Cd, Pb, Cr, Mn, Cu, Ni, Zn and Fe) for different environmental matrices (ground water, wastewater, sediment, soil, dust and leachates). Impact of solid waste dumping site on nearby human population has also been assessed. The results revealed that concentration of Pb, Fe, Cd, Mn and Cu surpassed the permissible limits of World Health Organization (WHO) and US Environmental Protection Agency (USEPA) in water, soil, sediments, while aforesaid metals in wastewater were above the National Environmental Quality Standards (NEQS). Our results for enrichment factor (EF) and geo-accumulation (I(geo)) values revealed that soils and sediments were contaminated with Cd, Pb, Ni and Mn. The Cd content caused a considerably high potential ecological risk (E(r)(i) ≥ 320) in soil and sediments. Pb and Cd caused high health risk (HR > 1) to local residents via dust and drinking water intake. Potential cancer risk for Pb was higher than USEPA standard values (1.0E-06-1.0E-04) through water intake. The Mehmood Booti dumping site is a potential source of toxic pollutants contamination to the surrounding population. It is recommended to take proper actions for its management to resolve this issue. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Navy SEAL Physical Fitness Guide

DTIC Science & Technology

1997-08-01

chafing. Thermal protection is not as good with the neck exposed . A good hood preserves a great deal of the swimmer’s heat. " Gloves may have webbed...the arms and also for the fins to chafe. Get thin booties without soles for fin use and consider using some vaseline or aquaphor ointment for other...specific activity that is to follow. This type of warm-up should be performed prior to high-intensity activities (e.g., O-Course, power-lifting, “ burn

Near-IR Direct Detection of Water Vapor in Tau Bootis b

DTIC Science & Technology

2014-02-24

transmission spectroscopy and secondary eclipses. Investigators have measured spectra of some of the larger transiting planets ( Charbonneau et al. 2002... Charbonneau , D., Désert, J.-M., et al. 2012, ApJ, 747, 35 Birkby, J. L., de Kok, R. J., Brogi, M., et al. 2013, MNRAS, 436, L35 Borucki, W. J...Williams, E., Hauser, H., & Shirts, P. 1997, ApJL, 474, L115 Butler, R. P., Wright, J. T., Marcy, G. W., et al. 2006, ApJ, 646, 505 Charbonneau , D

0{degree} binary encounter electron production in 30-MeV O{ital {sup q}}{sup +}+H{sub 2}, He, O{sub 2}, Ne, and Ar collisions

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

Zouros, T.J.; Wong, K.L.; Grabbe, S.

Double-differential cross sections (DDCS{close_quote}s) for the production of binary encounter electrons (BEE{close_quote}s) were measured for collisions of 30-MeV O{sup {ital q}+} projectiles with H{sub 2}, He, O{sub 2}, Ne, and Ar targets with {ital q}=4{endash}8 and an electron ejection angle of {theta}=0{degree} with respect to the beam direction. Particular interest focused on (a) the evaluation of the contributions of the different electron subshells of the multielectron targets, O{sub 2}, Ne, and Ar; (b) the study of the well-known enhancement of the BEE DDCS{close_quote}s with decreasing projectile charge-state {ital q}; here this dependence was tested for higher collision energies and newmore » targets; (c) the study of the dependence of the BEE {ital peak} {ital energy} on the particular target and projectile charge state. Results were analyzed in terms of the impulse approximation, in which target electrons in the projectile frame undergo 180{degree} elastic scattering in the field of the projectile ion. The electron scattering calculations were performed in a partial-wave treatment using the Hartree-Fock model. Good agreement with the data was found for the H{sub 2} and He targets, while for the multielectron targets O{sub 2}, Ne, and Ar only electrons whose velocity was lower than the projectile velocity needed to be included for good agreement. All measured BEE DDCS{close_quote}s were found to increase with decreasing projectile charge state, in agreement with other recent BEE results. The BEE peak energies were found to be independent of the projectile charge state for all targets utilized. {copyright} {ital 1996 The American Physical Society.}« less

Modeling the interaction of binary mixtures of estradiol and bisphenol A or its analogues in an in vitro estrogen mediated transcriptional activation assay (T47D-KBIuc).

EPA Science Inventory

Bisphenol A (BPA) is a ubiquitous monomer used to manufacture polycarbonate plastics. BPA is used in composites and sealants in dentistry, for epoxy resins used as protective liners in metallic cans, and as additives in various plastics. Approximately 1.7 billion pounds of BPA ar...

Oxidation-chlorination of binary Ni-Cr alloys in flowing Ar-O2-Cl2 gas mixtures at 1200 K

NASA Technical Reports Server (NTRS)

Mcnallan, M. J.; Lee, Y. Y.; Chang, Y. W.; Jacobson, N. S.; Doychak, J.

1991-01-01

Nickel-chromium alloys are resistant to oxidation because of the selective oxidation of chromium to form a protective Cr2O3 scale. In chlorine-containing environments, volatile corrosion products can also be formed. The mixed oxidation-chlorination of Ni-4.5Cr, Ni-13.8Cr, and Ni-26.5Cr (by weight) alloys in Ar-O2-Cl2 gas mixtures is investigated using thermogravimetric analysis and atmospheric-pressure-sampling mass spectrometry, followed by examination of the corrosion products using scanning electron microscopy and X-ray diffraction analysis. The overall kinetics of the corrosion are affected by the relative amounts of oxides and chlorides formed and the composition of the oxide corrosion products.

A MODEL OF WHITE DWARF PULSAR AR SCORPII

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

Geng, Jin-Jun; Huang, Yong-Feng; Zhang, Bing, E-mail: gengjinjun@gmail.com, E-mail: hyf@nju.edu.cn, E-mail: zhang@physics.unlv.edu

2016-11-01

A 3.56 hr white dwarf (WD)–M dwarf (MD) close binary system, AR Scorpii, was recently reported to show pulsating emission in radio, IR, optical, and UV, with a 1.97 minute period, which suggests the existence of a WD with a rotation period of 1.95 minutes. We propose a model to explain the temporal and spectral characteristics of the system. The WD is a nearly perpendicular rotator, with both open field line beams sweeping the MD stellar wind periodically. A bow shock propagating into the stellar wind accelerates electrons in the wind. Synchrotron radiation of these shocked electrons can naturally accountmore » for the broadband (from radio to X-rays) spectral energy distribution of the system.« less

High Resolution Spectroscopy of Vega-like Stars: Abundances and Circumstellar Gas

NASA Technical Reports Server (NTRS)

Dunkin, S. K.; Barlow, M. J.; Ryan, Sean G.

1996-01-01

Vega-like stars are main-sequence stars exhibiting excess infrared emission. In an effort to improve the information available on this class of star, 13 stars have been analyzed which have been classed as Vega-like, or have an infra-red excess attributable to dust in their circumstellar environment. In a separate paper stellar properties such as effective temperature and log g have been derived and in this poster we highlight the results of the photospheric abundance analysis also carried out during this work. King recently drew attention to the possible link between Vega-like stars and the photospheric metal-depleted class of A-stars, the Lambda Bootis stars. Since Vega-like stars are thought to have disks of dust, it might be expected that accretion of depleted gas onto the surface of these stars may cause this same phenomenon. In the 6 stars studied for depletions, none showed the extreme underabundance patterns observed in Lambda Bootis stars. However, depletions of silicon and magnesium were found in two of the sample, suggesting that these elements are in silicate dust grains in the circumstellar environment of these stars. Absorption lines attributed to circumstellar gas have been positively identified in three stars in our sample. Individual cases show evidence either of high-velocity outflowing gas, variability in the circumstellar lines observed, or evidence of circumstellar gas in excited lines of Fe II. No previous identification of circumstellar material has been made for two of the stars in question.

Foraging recruitment by the Giant Tropical Ant Paraponera clavata (Hymenoptera, Formicidae)

USGS Publications Warehouse

Barrett, Bruce A.; Jorgenson, Clive D.; Looman, Sandra J.

1985-01-01

Increased foraging of an exceptionally abundant, but ephemeral, food source by ants can result from foraging excitement that does not include pheromone trails, tandem running, or from recruitment of other workers along pheromone trails (Carrol and Janzen, 1973). They also provided rationale for two types of short-lived pheromone trails resulting in mass or group recruitment. These both seem to fall into the Type II foraging strategy described by Oster and Wilson (1978). Neither of these discussions conveniently allow for pheromone recruitment by relatively small colonies of a primitive monomorphic species such as Paraponera clavata. Our observations suggest that recruitment to an abundant ephemeral food source does occur naturally and can be induced artificially in colonies of P. clavata.Paraponera clavata is considered primitive (Wilson, 1958), particularly in foraging habits (Young and Hermann, 1980; Young, 1977). Hermann (1973, 1975) reported the P. clavata, unlike more advanced species, forages independently; following shot periods of apparent group activity outside of the colony (Young and Hermann, 1980). It reportedly does not return to a food source when only part has been harvested. After returning to its colony with booty, a single worker resumes foraging independently, with no observable tendency to return to partially harvested booty or without recruiting additional workers to collect the remaining food (Hermann, 1973; Young and Hermann, 1980). Reports of independent foraging, lack of forager recruitment, and apparent lack of food source fidelity resulted in the assumption that P. clavata probably lacks an effective pheromone trail communication system (Young and Hermann, 1980).

Long-term magnetic field monitoring of the Sun-like star ξ Bootis A

NASA Astrophysics Data System (ADS)

Morgenthaler, A.; Petit, P.; Saar, S.; Solanki, S. K.; Morin, J.; Marsden, S. C.; Aurière, M.; Dintrans, B.; Fares, R.; Gastine, T.; Lanoux, J.; Lignières, F.; Paletou, F.; Ramírez Vélez, J. C.; Théado, S.; Van Grootel, V.

2012-04-01

Aims: We aim to investigate the long-term temporal evolution of the magnetic field of the solar-type star ξ Bootis A, both from direct magnetic field measurements and from the simultaneous estimate of indirect activity indicators. Methods: We obtained seven epochs of high-resolution, circularly-polarized spectra from the NARVAL spectropolarimeter between 2007 and 2011, for a total of 76 spectra. Using approximately 6100 photospheric spectral lines covering the visible domain, we employed a cross-correlation procedure to compute a mean polarized line profile from each spectrum. The large-scale photospheric magnetic field of the star was then modelled by means of Zeeman-Doppler Imaging, allowing us to follow the year-to-year evolution of the reconstructed magnetic topology. Simultaneously, we monitored the width of several magnetically sensitive spectral lines, the radial velocity, the line asymmetry of intensity line profiles, and the chromospheric emission in the cores of the Ca II H and Hα lines. Results: During the highest observed activity states, in 2007 and 2011, the large-scale field of ξ Bootis A is almost completely axisymmetric and is dominated by its toroidal component. The toroidal component persists with a constant polarity, containing a significant fraction of the magnetic energy of the large-scale surface field through all observing epochs. The magnetic topologies reconstructed for these activity maxima are very similar, suggesting a form of short cyclicity in the large-scale field distribution. The mean unsigned large-scale magnetic flux derived from the magnetic maps varies by a factor of about 2 between the lowest and highest observed magnetic states. The chromospheric flux is less affected and varies by a factor of 1.2. Correlated temporal evolution, due to both rotational modulation and seasonal variability, is observed between the Ca II emission, the Hα emission and the width of magnetically sensitive lines. The rotational dependence of polarimetric magnetic measurements displays a weak correlation with other activity proxies, presumably due to the different spatial scales and centre-to-limb darkening associated with polarimetric signatures, as compared to non-polarized activity indicators. Better agreement is observed on the longer term. When measurable, the differential rotation reveals a strong latitudinal shear in excess of 0.2 rad d-1. Based on observations obtained at the Bernard Lyot Telescope (TBL, Pic du Midi, France) of the Midi-Pyrénées Observatory, which is operated by the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France.Tables 3-6 are available in electronic form at http://www.aanda.org

Large-scale Exploration of Neuronal Morphologies Using Deep Learning and Augmented Reality.

PubMed

Li, Zhongyu; Butler, Erik; Li, Kang; Lu, Aidong; Ji, Shuiwang; Zhang, Shaoting

2018-02-12

Recently released large-scale neuron morphological data has greatly facilitated the research in neuroinformatics. However, the sheer volume and complexity of these data pose significant challenges for efficient and accurate neuron exploration. In this paper, we propose an effective retrieval framework to address these problems, based on frontier techniques of deep learning and binary coding. For the first time, we develop a deep learning based feature representation method for the neuron morphological data, where the 3D neurons are first projected into binary images and then learned features using an unsupervised deep neural network, i.e., stacked convolutional autoencoders (SCAEs). The deep features are subsequently fused with the hand-crafted features for more accurate representation. Considering the exhaustive search is usually very time-consuming in large-scale databases, we employ a novel binary coding method to compress feature vectors into short binary codes. Our framework is validated on a public data set including 58,000 neurons, showing promising retrieval precision and efficiency compared with state-of-the-art methods. In addition, we develop a novel neuron visualization program based on the techniques of augmented reality (AR), which can help users take a deep exploration of neuron morphologies in an interactive and immersive manner.

AR Sco as a possible seed of highly magnetized white dwarf

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Banibrata; Rao, A. R.; Bhatia, Tanayveer Singh

2017-12-01

We explore the possibility that the recently discovered white dwarf pulsar AR Sco acquired its high spin and magnetic field due to repeated episodes of accretion and spin-down. An accreting white dwarf can lead to a larger mass and consequently a smaller radius thus causing an enhanced rotation period and a magnetic field. This spinning magnetic white dwarf temporarily can inhibit accretion, spin down and eventually, the accretion can start again due to the shrinking of the binary period by gravitational radiation. A repetition of the above cycle can eventually lead to a high magnetic field white dwarf, recently postulated to be the reason for overluminous type Ia supernovae. We also point out that these high magnetic field spinning white dwarfs are attractive sites for gravitational radiation.

Production of Ar and Xe metastables in rare gas mixtures in a dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Mikheyev, Pavel A.; Han, Jiande; Clark, Amanda; Sanderson, Carl; Heaven, Michael C.

2017-12-01

Optically pumped all-rare-gas lasers (OPRGL) utilize metastable atoms of the heavier rare gases as lasing species. The required number density of metastables for efficient laser operation is 1012-1013 cm-3 in He buffer gas at pressures in the 400-1000 Torr range. Such metastable densities are easily produced in a nanosecond pulsed discharge, even at pressures larger than atmospheric, but problems appear when one is trying to achieve continuous production. The reason for low production efficiency in many types of continuous discharge at atmospheric pressure is the low value of the E/N parameter (<5-6 Td). In the present work, we have examined the possibility of using a dielectric barrier discharge (DBD) to provide near continuous, high densities of Ar and Xe metastables. Experiments were performed using a 20 kHz DBD in binary Ar and Xe mixtures with He, and in ternary Ar:Xe:He mixtures at pressures up to 1 atmosphere. Concentrations were measured by means of tunable diode laser absorption spectroscopy. Time-averaged [Ar(1s5)] and [Xe(1s5)] number densities on the order of 1012 cm-3 were readily achieved. The temporal behavior of [Xe(1s5)] throughout the DBD cycle was observed. The results demonstrate the feasibility of using DBDs for OPRGL development. Spectral scans over the absorption lines were also used to examine the pressure broadening coefficients for the 912.3 nm Ar line in He and the Xe 904.5 nm line in Ne and He.

Phase-transition oscillations induced by a strongly focused laser beam

NASA Astrophysics Data System (ADS)

Devailly, Clémence; Crauste-Thibierge, Caroline; Petrosyan, Artyom; Ciliberto, Sergio

2015-11-01

We report the observation of a surprising phenomenon consisting in a oscillating phase transition which appears in a binary mixture when this is enlightened by a strongly focused infrared laser beam. The mixture is poly-methyl-meth-acrylate (PMMA)-3-octanone, which has an upper critical solution temperature at Tc=306.6 K and volume fraction ϕc=12.8 % [Crauste et al., arXiv:1310.6720, 2013]. We describe the dynamical properties of the oscillations, which are produced by a competition between various effects: the local accumulation of PMMA produced by the laser beam, thermophoresis, and nonlinear diffusion. We show that the main properties of this kind of oscillations can be reproduced in the Landau theory for a binary mixture in which a local driving mechanism, simulating the laser beam, is introduced.

Triply differential measurements of single ionization of argon by 1-keV positron and electron impact

NASA Astrophysics Data System (ADS)

Gavin, J.; de Lucio, O. G.; DuBois, R. D.

2017-06-01

By establishing coincidences between target ions and scattered projectiles, and coincidences between target ions, scattered projectiles, and ejected electrons, triply differential cross-section (TDCS) information was generated in terms of projectile energy loss and scattering angles for interactions between 1-keV positrons and electrons and Ar atoms. The conversion of the raw experimental information to the TDCS is discussed. The single-ionization TDCS exhibits two distinguishable regions (lobes) where binary and recoil interactions can be described by two peaks. A comparison of the positron and electron impact data shows that the relative intensity of both binary and recoil interactions decreases exponentially as a function of the momentum transfer and is larger when ionization is induced by positron impact, when compared with electron impact.

Multiphase computer-generated holograms for full-color image generation

NASA Astrophysics Data System (ADS)

Choi, Kyong S.; Choi, Byong S.; Choi, Yoon S.; Kim, Sun I.; Kim, Jong Man; Kim, Nam; Gil, Sang K.

2002-06-01

Multi-phase and binary-phase computer-generated holograms were designed and demonstrated for full-color image generation. Optimize a phase profile of the hologram that achieves each color image, we employed a simulated annealing method. The design binary phase hologram had the diffraction efficiency of 33.23 percent and the reconstruction error of 0.367 X 10-2. And eight phase hologram had the diffraction efficiency of 67.92 percent and the reconstruction error of 0.273 X 10-2. The designed BPH was fabricated by micro photolithographic technique with a minimum pixel width of 5micrometers . And the it was reconstructed using by two Ar-ion lasers and a He-Ne laser. In addition, the color dispersion characteristic of the fabricate grating and scaling problem of the reconstructed image were discussed.

Turmeric powder and its derivatives from Curcuma longa rhizomes: Insecticidal effects on cabbage looper and the role of synergists.

PubMed

de Souza Tavares, Wagner; Akhtar, Yasmin; Gonçalves, Gabriel Luiz Padoan; Zanuncio, José Cola; Isman, Murray B

2016-11-02

Curcuma longa has well-known insecticidal and repellent effects on insect pests, but its impact on Trichoplusia ni is unknown. In this study, the compound ar-turmerone, extracted and purified from C. longa rhizomes, was identified, and its insecticidal effects, along with turmeric powder, curcuminoid pigments and crude essential oil were evaluated against this important agricultural pest. The role of natural (sesamol and piperonal) and synthetic [piperonyl butoxide (PBO)] synergists under laboratory and greenhouse conditions were also evaluated. The concentration of ar-turmerone in C. longa rhizomes harvested was 0.32% (dwt). Turmeric powder and its derivatives caused 10-20% mortality in third instar T. ni at a very low dose (10 μg/larva). Addition of PBO increased toxicity of turmeric powder and its derivatives (90-97% mortality) in most binary combinations (5 μg of turmeric powder or its derivatives +5 μg of PBO), but neither piperonal nor sesamol were active as synergists. The compound ar-turmerone alone and the combination with PBO reduced larval weight on treated Brassica oleracea in the laboratory and in greenhouse experiments, compared with the negative control. The compound ar-turmerone could be used as a low cost botanical insecticide for integrated management of cabbage looper in vegetable production.

Investigations of the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies

NASA Astrophysics Data System (ADS)

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-01

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species.

Visual Double Stars - St. Mary's High School Astronomy Club

NASA Astrophysics Data System (ADS)

Bensel, Holly; Tran, Thanh; Hicks, Sean; He, Yifan; Moczygemba, Mitchell; Shi, Yuqi; Sternenberg, Leah; Watson, Kaycia; Rooney, Kieran; Birmingham, Paige; You, Ruiyang

2017-01-01

The St. Mary’s School Astronomy Club is working towards measuring positions and angles of relatively unstudied visual binary stars. We are starting with confirming prior results we obtained at the Pine Mountain Observatory Summer Science Research Workshop in 2009 - 2012 on ARY 52 (Frey et al. 2009, JDSO), Iota Bootis (Bensel et al. 2009, JDSO), and Mizar (Bensel et al. 2009, JDSO). We are also comparing our results with those published in the Washington Double Star Catalog (Mason 2009). We are using Pine Mountain Observatory’s remote imaging 14-inch Meade Schmidt-Cassegrain telescope equipped with a CCD camera operated by Scott Fisher at the University of Oregon and local astronomer Sean Curry’s 12.5" PlaneWave CDK telescope. We are practicing using tools such as astrometry.net and DS9 software to measure positions and angles on known double stars with well established values before attempting new measurements. Our next project will be to study “neglected visual double stars,” lesser studied double stars with fainter magnitudes. (A neglected double star is one that has not been observed extensively or recently.)Double star analysis is relatively straight forward and can be performed with equipment available to most high schools.Educational outcomes include instrument setup, orientation, instruction, observations, analysis, presentation of data, and writing up findings for publication. Accurate recording of data is a useful and important life skill for all students to learn. Another important life skill is learning to work together to accomplish a specific goal. This project allows novice and experienced observers to work hand-in-hand to accomplish a specific goal, such as the publishing of a research paper in the Journal of Double Star Observations.

Evaluation of interatomic potentials for rainbow scattering under axial channeling at KCl(0 0 1) surface by three-dimensional computer simulations based on binary collision approximation

NASA Astrophysics Data System (ADS)

Takeuchi, Wataru

2017-05-01

The rainbow angles corresponding to prominent peaks in the angular distributions of scattered projectiles with small angle, attributed to rainbow scattering (RS), under axial surface channeling conditions are strongly influenced by the interatomic potentials between projectiles and target atoms. The dependence of rainbow angles on normal energy of projectile energy to the target surface, being experimentally obtained by Specht et al. for RS of He, N, Ne and Ar atoms under <1 0 0> and <1 1 0> axial channeling conditions at a KCl(0 0 1) surface with projectile energies of 1-60 keV, was evaluated by the three-dimensional computer simulations using the ACOCT code based on the binary collision approximation with interatomic pair potentials. Good agreement between the ACOCT results using the ZBL pair potential and the individual pair potentials calculated from Hartree-Fock (HF) wave functions and the experimental ones was found for RS of He, N and Ne atoms from the atomic rows along <1 0 0> direction. For <1 1 0> direction, the ACOCT results employing the Moliere pair potential with adjustable screening length of O'Connor-Biersack (OB) formula, the ZBL pair potential and the individual HF pair potentials except for Ar → KCl using the OB pair potential are nearly in agreement with the experimental ones.

VLA radio observations of AR Scorpii

NASA Astrophysics Data System (ADS)

Stanway, E. R.; Marsh, T. R.; Chote, P.; Gänsicke, B. T.; Steeghs, D.; Wheatley, P. J.

2018-03-01

Aims: AR Scorpii is unique amongst known white dwarf binaries in showing powerful pulsations extending to radio frequencies. Here we aim to investigate the multi-frequency radio emission of AR Sco in detail, in order to constrain its origin and emission mechanisms. Methods: We present interferometric radio frequency imaging of AR Sco at 1.5, 5 and 9 GHz, analysing the total flux and polarization behaviour of this source at high time resolution (10, 3 and 3 s), across a full 3.6 h orbital period in each band. Results: We find strong modulation of the radio flux on the orbital period and the orbital sideband of the white dwarf's spin period (also known as the "beat" period). This indicates that, like the optical flux, the radio flux arises predominantly from on or near the inner surface of the M-dwarf companion star. The beat-phase pulsations of AR Sco decrease in strength with decreasing frequency. They are strongest at 9 GHz and at an orbital phase 0.5. Unlike the optical emission from this source, radio emission from AR Sco shows weak linear polarization but very strong circular polarization, reaching 30% at an orbital phase 0.8. We infer the probable existence of a non-relativistic cyclotron emission component, which dominates at low radio frequencies. Given the required magnetic fields, this also likely arises from on or near the M-dwarf. A table of the flux time series is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A66

VizieR Online Data Catalog: λ Bootis stars: the southern survey I. (Gray+, 2017)

NASA Astrophysics Data System (ADS)

Gray, R. O.; Riggs, Q. S.; Koen, C.; Murphy, S. J.; Newsome, I. M.; Corbally, C. J.; Cheng, K.-P.; Neff, J. E.

2017-10-01

Observations were carried out with the South African Astronomical Observatory (SAAO) SpCCD grating spectrograph, attached to the SAAO 1.9m telescope. Grating 6 was employed, which yields a resolution of about 2Å/2 pixels and a spectral range from 3600 to 5400Å. Time was granted for four observing runs of about 5 days each in 2013 December, and 2014 March, June, and September, enabling us to cover the entire southern sky. A total of 291 program stars, plus a number of MK standards, were observed over the four runs. (6 data files).

jsc2013e090230

NASA Image and Video Library

2013-10-17

At the Gagarin Cosmonaut Training Center in Star City, Russia, Expedition 38/39 Soyuz Commander Mikhail Tyurin (center) is assisted by a technician as he dons protective booties for the start of final qualification simulation exams Oct. 17, 2013. Tyurin is joined by his crewmates, Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency (left) and NASA Flight Engineer Rick Mastracchio (right). The trio is scheduled to launch on Nov. 7, local time, from the Baikonur Cosmodrome in Kazakhstan on the Soyuz TMA-11M spacecraft for a six-month mission on the International Space Station. NASA/Stephanie Stoll

Turmeric powder and its derivatives from Curcuma longa rhizomes: Insecticidal effects on cabbage looper and the role of synergists

PubMed Central

de Souza Tavares, Wagner; Akhtar, Yasmin; Gonçalves, Gabriel Luiz Padoan; Zanuncio, José Cola; Isman, Murray B.

2016-01-01

Curcuma longa has well-known insecticidal and repellent effects on insect pests, but its impact on Trichoplusia ni is unknown. In this study, the compound ar-turmerone, extracted and purified from C. longa rhizomes, was identified, and its insecticidal effects, along with turmeric powder, curcuminoid pigments and crude essential oil were evaluated against this important agricultural pest. The role of natural (sesamol and piperonal) and synthetic [piperonyl butoxide (PBO)] synergists under laboratory and greenhouse conditions were also evaluated. The concentration of ar-turmerone in C. longa rhizomes harvested was 0.32% (dwt). Turmeric powder and its derivatives caused 10–20% mortality in third instar T. ni at a very low dose (10 μg/larva). Addition of PBO increased toxicity of turmeric powder and its derivatives (90–97% mortality) in most binary combinations (5 μg of turmeric powder or its derivatives +5 μg of PBO), but neither piperonal nor sesamol were active as synergists. The compound ar-turmerone alone and the combination with PBO reduced larval weight on treated Brassica oleracea in the laboratory and in greenhouse experiments, compared with the negative control. The compound ar-turmerone could be used as a low cost botanical insecticide for integrated management of cabbage looper in vegetable production. PMID:27804972

Investigations of the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies.

PubMed

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-05

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species. Copyright © 2016 Elsevier B.V. All rights reserved.

A quantification of predation rates, indirect positive effects on plants, and foraging variation of the giant tropical ant, Paraponera clavata

PubMed Central

Dyer, Lee A.

2002-01-01

While a clear consensus is emerging that predators can play a major role in shaping terrestrial communities, basic natural history observations and simple quantifications of predation rates in complex terrestrial systems are lacking. The potential indirect effect of a large predatory ant, Paraponera clavata Fabricius (Formicidae: Ponerinae), on herbivores was determined on rainforest trees at La Selva Biological Station in Costa Rica and Barro Colorado Island in Panama. Prey and other food brought back to nests by 75 colonies of P. clavata were quantified, taking into account temporal, seasonal, and microhabitat variation for both foraging activity and composition of foraging booty. The dispersion and density of ant colonies and combined density with the mean amounts of prey retrieval were used to calculate rates of predation per hectare in the two forests. In addition, herbivory was measured on trees containing P. clavata and on trees where the ants were not foraging. Colonies at La Selva brought back significantly more nectar plus prey than those at Barro Colorado Island, but foraging patterns were similar in the two forests. At both forests, the ants were more active at night, and there was no significant seasonal or colonial variation in consumption of nectar, composition of foraging booty, and overall activity of the colonies. At La Selva, trees containing P. clavata colonies had the same levels of folivory as nearest neighbor trees without P. clavata but had significantly lower folivory than randomly selected trees. Predation by this ant was high in both forests, despite its omnivorous diet. This insect predator is part of potentially important top-down controls in these wet and moist forests. PMID:15455052

A quantification of predation rates, indirect positive effects on plants, and foraging variation of the giant tropical ant, Paraponera clavata.

PubMed

Dyer, Lee A

2002-01-01

While a clear consensus is emerging that predators can play a major role in shaping terrestrial communities, basic natural history observations and simple quantifications of predation rates in complex terrestrial systems are lacking. The potential indirect effect of a large predatory ant, Paraponera clavata Fabricius (Formicidae: Ponerinae), on herbivores was determined on rainforest trees at La Selva Biological Station in Costa Rica and Barro Colorado Island in Panama. Prey and other food brought back to nests by 75 colonies of P. clavata were quantified, taking into account temporal, seasonal, and microhabitat variation for both foraging activity and composition of foraging booty. The dispersion and density of ant colonies and combined density with the mean amounts of prey retrieval were used to calculate rates of predation per hectare in the two forests. In addition, herbivory was measured on trees containing P. clavata and on trees where the ants were not foraging. Colonies at La Selva brought back significantly more nectar plus prey than those at Barro Colorado Island, but foraging patterns were similar in the two forests. At both forests, the ants were more active at night, and there was no significant seasonal or colonial variation in consumption of nectar, composition of foraging booty, and overall activity of the colonies. At La Selva, trees containing P. clavata colonies had the same levels of folivory as nearest neighbor trees without P. clavata but had significantly lower folivory than randomly selected trees. Predation by this ant was high in both forests, despite its omnivorous diet. This insect predator is part of potentially important top-down controls in these wet and moist forests.

Use of a Slick-Plate as a Contingency Exercise Surface for the Treadmill With Vibration Isolation System

NASA Technical Reports Server (NTRS)

Loehr, James A.; Lee, Stuart M. C.; Schneider, Suzanne M.

2003-01-01

The treadmill with vibration isolation system (TVIS) was developed to counteract cardiovascular, musculoskeletal, and neurovestibular deconditioning during long-duration missions to the International Space Station (ISS). However, recent hardware failures have necessitated the development of a short-term, temporary contingency exercise countermeasure for TVIS until nominal operations could be restored. The purpose of our evaluation was twofold: 1) to examine whether a slick-plate/contingency exercise surface (CES) could be used as a walking/running surface and could elicit a heart rate (HR) greater than or equal to 70% HR maximum and 2) to determine the optimal hardware configuration, in microgravity, to simulate running/walking in a 1-g environment. One subject (male) participated in the slick surface evaluation and two subjects (one male, one female) participated in the microgravity evaluation of the slick surface configuration. During the slick surface evaluation, the subject was suspended in a parachute harness and bungee cord configuration to offset the subject#s body weight. Using another bungee cord configuration, we added a vertical load back to the subject, who was then asked to run for 20 minutes on the slick surface. The microgravity evaluation simulated the ISS TVIS, and we evaluated two different slick surfaces (Teflon surface and an aluminum surface coated with Tufram) for use as a CES. We evaluated each surface with the subject walking and running, with and without a handrail, and while wearing either socks or nylon booties over shoes. In the slick surface evaluation, the subject ran for 20 minutes and reached a maximum HR of 170 bpm. In the microgravity evaluation, the subjects chose the aluminum plate coated with Tufram as the CES, while wearing a pair of nylon booties over running shoes and using a handrail, as the optimal hardware configuration.

Negative Entropy of Life

NASA Astrophysics Data System (ADS)

Goradia, Shantilal

2015-10-01

We modify Newtonian gravity to probabilistic quantum mechanical gravity to derive strong coupling. If this approach is valid, we should be able to extend it to the physical body (life) as follows. Using Boltzmann equation, we get the entropy of the universe (137) as if its reciprocal, the fine structure constant (ALPHA), is the hidden candidate representing the negative entropy of the universe which is indicative of the binary information as its basis (http://www.arXiv.org/pdf/physics0210040v5). Since ALPHA relates to cosmology, it must relate to molecular biology too, with the binary system as the fundamental source of information for the nucleotides of the DNA as implicit in the book by the author: ``Quantum Consciousness - The Road to Reality.'' We debate claims of anthropic principle based on the negligible variation of ALPHA and throw light on thermodynamics. We question constancy of G in multiple ways.

3D Modeling of Forbidden Line Emission in the Binary Wind Interaction Region of Eta Carinae

NASA Technical Reports Server (NTRS)

Madura, Thomas; Gull, T. R.; Owocki, S.; Okazaki, A. T.; Russell, C. M. P.

2010-01-01

We present recent work using three-dimensional (3D) Smoothed Particle Hydrodynamics (SPH) simulations to model the high ([Fe III], [Ar III], [Ne III] and [S III]) and low ([Fe II], [Ni II]) ionization forbidden emission lines observed in Eta Carinae using the HST/STIS. These structures are interpreted as the time-averaged, outer extensions of the primary wind and the wind-wind interaction region directly excited by the FUV of the hot companion star of this massive binary system. We discuss how analyzing the results of the 3D SPH simulations and synthetic slit spectra and comparing them to the spectra obtained with the HST/STIS helps us determine the absolute orientation of the binary orbit and helps remove the degeneracy inherent to models based solely on the observed RXTE X-ray light curve. A key point of this work is that spatially resolved observations like those with HST/STIS and comparison to 3D models are necessary to determine the alignment or misalignment of the orbital angular momentum axis with the Homunculus, or correspondingly, the alignment of the orbital plane with the Homunculus skirt.

Binary Star Orbits. 3. Revisiting the Remarkable Case of Tweedledum and Tweedledee

DTIC Science & Technology

2010-06-11

Observation Date 0.00 0.05 0.10 0.15 0.20 S ep ar at io n D iff er en ce FIN 332 Aa,Ab Unresolved Aa,Ab bB,aBdevlosernU bB,aB 233 NIF 1960 1970 1980 1990...2000 2010 Observation Date 0 50 100 150 200 P os iti on A ng le D iff er en ce FIN 332 Aa,Ab Unresolved Aa,Ab bB,aBdevlosernU bB,aB 233 NIF Figure

Methodology Investigation. Chamber Versus Environmental Deterioration Tests

DTIC Science & Technology

1979-01-01

instructions do not apply to the record copy (AR 340-18). UNCLASSIFIED S.CURITY CLASSIFICATION OF I HIS PAGE ("eiln Daoe FKnterpd) I PAGE READ INSTRUCTIONS...D 4 - from P. Pin F 0-0 Figure 14 ->TIL 302 TL3 * 10 I , C 1:1 FiL r 16. Diia0lcto i yt m c e- t 1C 234 -.>11- tandem. The binary coded decimal ...Mexico State University and/or the University I of Texas at El Paso will be contracted to assist in this investigation by performing detailed, time

Collision-Induced Spectra: AN Avenue to Investigate Microscopic-Scale Diffusion in Fluids

NASA Astrophysics Data System (ADS)

Herrebout, Wouter A.; van der Veken, Benjamin J.; Kouzov, Alexander

2014-06-01

New data on the IR spectra induced by intermolecular interactions in liquid cryogenic mixtures at T=89 K (O2 in LAr and LN2 and binary O2-Ar solutions in LN2) are reported. The induced fundamental bands appear as diffuse pedestals (with FWHH≈100 cm-1) on which weak, paradoxically sharp lines (FWHH≈2 cm-1) develop at the 2326 and 1552 cm-1 frequencies of the free-molecule vibrational transitions in N2 and O2, respectively. In LAr and LN2 these lines were carefully separated and studied at varied O2 concentrations up to c=0.23 mole fractions (mf). While the 1552 cm-1 line scales as c[O2]2 and thus is induced by the O2-O2 interactions in a bulk of cryosolvent (Ar, N2), the 2326 cm-1 feature varies linearly with c[O2] and hence is caused by interaction of a guest (O2) with a vibrating host (N_2). The impurity induction mechanism was further supported by our data on the binary O2-Ar solutions in LN2 %for which the spectra were recorded at the fixed c[O2] (0.03 and 0.06 mf) and the varied c% [Ar]≤0.2 mf. Both series revealed the same (linear) enhancement of the sharp N2 line by argon, in an accord with our previous studies of the Ar-LN2 system. The results suggest that the resonance 2326 cm-1 feature is primarily due to the local distortion of the first coordination sphere around a vibrating N_2 by a guest molecule. We also notice that the resonance lines should be due to the dispersion- and overlap-induced dipole moments independent on the rotational degrees of freedom. As our previous studies of the H2-LNe system showed, the unusual line sharpness is a conspicuous manifestation of the relative solvent-solute and solute-solute translations dramatically retarded in a liquid by a fast velocity relaxation, an effect directly related to the microscopic-scale diffusion. The collision-induced spectra thus open up new vistas for studies of microscopic liquid dynamics. W.A. Herrebout, A.A. Stolov, E.J. Sluyts, and B.J. van der Veken, Chem. Phys. Lett. 295, 223 (1998) J.E. Bohr and K.L.C. Hunt, J. Chem. Phys. 86, 5441 (1987) W. A. Herrebout, B. J. van der Veken, and A. P. Kouzov, Phys.Rev. Lett. 101, 093001 (2008) W. A. Herrebout, B. J. van der Veken, and A. P. Kouzov, J. Chem. Phys. 137, 084509 (2012)

Minute Temperature Fluctuations Detected in Eta Bootis

NASA Astrophysics Data System (ADS)

1994-11-01

A group of astronomers from the Aarhus University (Denmark) and the European Southern Observatory (2) have for the first time succeeded in detecting solar-type oscillations in another star. They observed the temperature of the bright northern star Eta Bootis during six nights with the 2.5-metre Nordic Optical Telescope at the Roque de los Muchachos observatory on the island of La Palma (Canary Islands) and were able to show that it varies periodically by a few hundredths of a degree. These changes are caused by pressure waves in the star and are directly dependent on its inner structure. A detailed analysis by the astronomers has shown that the observed effects are in good agreement with current stellar models. This is a most important, independent test of stellar theory. The Sun is an Oscillating Star About twenty years ago, it was discovered that the nearest star, our Sun, oscillates like the ringing of a bell with a period of about 5 minutes. The same phenomenon is known in the Earth, which begins to vibrate after earthquakes; in this way seismologists have been able to discern a layered structure in the Earth's interior. The recent impacts of a comet on Jupiter most likely had a similar effect on that planet. The observed solar oscillations concern the entire gaseous body of the Sun, but we can of course only observe them on its surface. It has been found that each mode moves the surface up and down by less than 25 metres; the combined motion is very complicated, because there are many different, simultaneous modes, each of which has a slightly different period. The exact values of these periods are sensitive to the speed of sound in the Sun's interior, which in turn depends on the density of the material there. Thus, by measuring the periods of solar oscillations, we may probe the internal structure of the Sun, that is otherwise inaccessible to observations. Why does the Sun oscillate and what is the cause of these oscillations ? We do not know yet, but it is thought that the driving force is convective motion in the interior. For a better understanding of this basic phenomenon, we may compare the Sun with a pot of boiling water on the stove. The "bubbles" in the pot, known as solar convection cells, rise upwards towards the surface and jostle the Sun from the inside. This causes it to oscillate, although we still do not know the details of how these oscillations are triggered. We can just be grateful they exist, and by measuring their periods we obtain important information about the inside of the Sun. A great deal of progress has recently been made in this way. Do Other Stars Oscillate Like the Sun? The Sun is a normal star. It oscillates, and we would therefore expect that other, similar stars also do. Indeed, large-amplitude stellar oscillations have been known for centuries to manifest themselves as significant changes in the observed brightness of some "variable stars". However, in most cases, for example in the so-called Cepheid and RR Lyrae variable stars, only one or two periods have been detected. What distinguishes solar-type oscillations is the large number of observed periods, that potentially gives a great deal of information about the stellar interiors, as well as their much smaller amplitudes. During the past decade, astronomers have been trying to detect this type of oscillations in stars other than the Sun, but with little success. Such oscillations are much more difficult to detect, because the stars are much further away and therefore fainter than the Sun. Most observational attempts have tried to detect the movement of the stellar surface directly, by measuring velocity (Doppler) shifts in the stellar spectra, cf. the Appendix. Due to the up-down motion of less than 1 metre/sec, the spectral lines should shift backwards and forwards by about 1 part in 300,000,000, or less than 0.00002 nanometres in red light, a minuscule shift that is very difficult to measure with current astronomical instrumentation, even in the very brightest stars. Faced with this problem, the Danish/ESO group came up with an entirely new method. It relies on the fact that the oscillations are sound waves which deposit energy in the various stellar layers and therefore intermittently heat the star very slightly. For example, each mode changes the temperature on the surface of the Sun by about 0.005 degrees during the oscillation. But how to measure such small temperature changes? It turns out that this is possible by recording the strengths of the spectral lines, specifically, the absorption lines due to hydrogen. Their strengths change slightly with the changes in temperature (see Appendix). Although this is still a very small effect, it should be easier to measure than the velocity shifts. Yes, Eta Bootis does! To test their method, the astronomers used the ESO 3.5-metre New Technology Telescope (NTT) with the ESO Multi-Mode Instrument (EMMI) to observe a bright star for a few hours. This was too short to detect actual oscillations, but it did show that the technique works: it was in principle possible to measure the temperature accurately enough. The target for the real observations was the 2.68-magnitude, naked-eye star Eta Bootis (Greek letter "eta"). It has the common name of Muphrid and is located just north of the celestial equator in Bootes, one of the oldest constellation names still in use (it was mentioned already in the Odyssey). This particular star is somewhat more evolved and bigger than the Sun and, according to stellar theory, should have stronger oscillations than the Sun, hence increasing the chance that they could be detected. The observations were performed with the 2.5-metre Nordic Optical Telescope (NOT) during six, mostly clear nights in April 1994. A careful data analysis has now shown that the temperature of Eta Bootis is indeed changing periodically, around a mean value of about 6000 K. It seems to be oscillating in at least ten different modes simultaneously, with periods around 20 minutes. These periods are longer than those of the Sun, as expected for a star that is larger and heavier than the Sun. The figure accompanying this Press Release shows these oscillations in the form of a "power spectrum", i.e., the amount of temperature change at different values of the period. Most of the highest peaks correspond to the real oscillations in the star. The changes (fluctuations) of the temperature of Eta Bootis vary with the oscillation mode and, at the time of these observations, were mostly between 0.03 and 0.08 degrees. This diagramme provides the first strong evidence ever for solar-type oscillations in a star other than the Sun. An article with the detailed results will soon appear in the "Astronomical Journal". Agreement with Stellar Theory The measured periods of the main oscillation modes give important information about the interior of Eta Bootis. Theoretical models of the star have now been compared with these observations and the astronomers were pleased to find that the agreement is excellent, implying that current stellar theory is remarkably good. This shows that we apparently understand stars quite well, but there is of course still much to be learned. Future observations of this kind, with ground-based telescopes and possibly in a more distant future also from space, promise to open up a new and exciting way of studying stars. From now on, we will be able "to look inside" stars in great detail. Appendix: Spectral Analysis Dark spectral lines were first seen in the solar spectrum by the German physicist Johann Fraunhofer in 1814. Later, in the mid-nineteenth century, such lines were also seen in the spectra of other stars. It is now known that they are due to the upper, cooler layers in the solar and stellar atmospheres, whose atoms and molecules absorb the radiation from the hotter, deeper layers at specific wavelengths. These wavelengths serve as "footprints" of these atoms and molecules and allow astronomers to determine which chemical elements are present in the Sun and the stars. The exact position of a dark line in the spectrum (its wavelength) depends on the velocity along the line of sight of the corresponding atoms or molecules. If they move in our direction, the wavelength of the line becomes slightly shorter; if they move away from us, it will be a little longer. This is referred to as the Doppler effect and is well known also from sound waves, cf. the sound of a passing ambulance. Moreover, at a given stellar surface temperature, the "strengths" of these lines (a measure of how dark and broad they are) permit to measure directly the quantities present of the individual elements and hence the chemical composition. Conversely, observed changes in the line-strengths of the spectra of certain peculiar types of stars indicate changes in the composition, or of the ambient temperature. Until now, all observed temperature changes in stars have been much larger than those caused by solar-type oscillations as now observed in Eta Bootis, and of different nature. (1) This is a joint Press Release of ESO and the Institute of Physics and Astronomy, Aarhus University, Denmark (IFA). (2) The group consists of Hans Kjeldsen, Michael Viskum and Soren Frandsen (IFA), Jorgen Christensen-Dalsgaard (IFA; and Theoretical Astrophysics Center, Danish National Research Foundation), and Tim Bedding (ESO). Hans Kjeldsen was supported by a grant from the Carlsberg Foundation. Figure Caption This figure shows the oscillations now observed in the star Eta Bootis, in the form of a "power spectrum", i.e., the amount of temperature change at different values of the period. See the text of the Press Release for more details.

Effect of air humidity on the removal of carbon tetrachloride from air using Cu-BTC metal-organic framework.

PubMed

Martín-Calvo, Ana; García-Pérez, Elena; García-Sánchez, Almudena; Bueno-Pérez, Rocío; Hamad, Said; Calero, Sofia

2011-06-21

We have used interatomic potential-based simulations to study the removal of carbon tetrachloride from air at 298 K, using Cu-BTC metal organic framework. We have developed new sets of Lennard-Jones parameters that accurately describe the vapour-liquid equilibrium curves of carbon tetrachloride and the main components from air (oxygen, nitrogen, and argon). Using these parameters we performed Monte Carlo simulations for the following systems: (a) single component adsorption of carbon tetrachloride, oxygen, nitrogen, and argon molecules, (b) binary Ar/CCl(4), O(2)/CCl(4), and N(2)/CCl(4) mixtures with bulk gas compositions 99 : 1 and 99.9 : 0.1, (c) ternary O(2)/N(2)/Ar mixtures with both, equimolar and 21 : 78 : 1 bulk gas composition, (d) quaternary mixture formed by 0.1% of CCl(4) pollutant, 20.979% O(2), 77.922% N(2), and 0.999% Ar, and (e) five-component mixtures corresponding to 0.1% of CCl(4) pollutant in air with relative humidity ranging from 0 to 100%. The carbon tetrachloride adsorption selectivity and the self-diffusivity and preferential sitting of the different molecules in the structure are studied for all the systems.

Risk Factors for the Rupture of Intracranial Aneurysms Using Computed Tomography Angiography.

PubMed

Wang, Guang-Xian; Wen, Li; Yang, Liu; Zhang, Qi-Chuang; Yin, Jin-Bo; Duan, Chun-Mei; Zhang, Dong

2018-02-01

To study the clinical and morphologic characteristics associated with risk factors for the rupture of intracranial aneurysms (IAs). A total of 1115 consecutive patients with 1282 IAs were reviewed from August 2011 to February 2016. The patients and IAs were divided into ruptured and unruptured groups. Based on the clinical and morphologic findings, the risk factors for IA rupture were assessed using statistical methods. Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were associated with ruptured IAs. IAs located in the anterior cerebral artery, the anterior communicating artery, the posterior communicating artery, and the internal carotid artery were associated with ruptured IAs. Ruptures were also associated with arterial bifurcations, irregular aneurysm shapes, and all continuous data, except neck width. Binary logistic regression showed that IAs located at bifurcations (odds ratio [OR], 1.804), with irregular shapes (OR, 4.677), with high aspect ratios (ARs) (OR, 5.037) or with small mean diameters (MDs) (OR, 0.495) are more prone to rupture. Receiver operating characteristic analysis showed that the threshold values of the AR and MD were 1 and 3.70 mm, respectively. Morphologic characteristics, such as being located at bifurcations, being irregularly shaped, having a high AR (>1), and having a small MD (<3.70 mm), were better predictors of rupture. Copyright © 2017 Elsevier Inc. All rights reserved.

PCANet: A Simple Deep Learning Baseline for Image Classification?

PubMed

Chan, Tsung-Han; Jia, Kui; Gao, Shenghua; Lu, Jiwen; Zeng, Zinan; Ma, Yi

2015-12-01

In this paper, we propose a very simple deep learning network for image classification that is based on very basic data processing components: 1) cascaded principal component analysis (PCA); 2) binary hashing; and 3) blockwise histograms. In the proposed architecture, the PCA is employed to learn multistage filter banks. This is followed by simple binary hashing and block histograms for indexing and pooling. This architecture is thus called the PCA network (PCANet) and can be extremely easily and efficiently designed and learned. For comparison and to provide a better understanding, we also introduce and study two simple variations of PCANet: 1) RandNet and 2) LDANet. They share the same topology as PCANet, but their cascaded filters are either randomly selected or learned from linear discriminant analysis. We have extensively tested these basic networks on many benchmark visual data sets for different tasks, including Labeled Faces in the Wild (LFW) for face verification; the MultiPIE, Extended Yale B, AR, Facial Recognition Technology (FERET) data sets for face recognition; and MNIST for hand-written digit recognition. Surprisingly, for all tasks, such a seemingly naive PCANet model is on par with the state-of-the-art features either prefixed, highly hand-crafted, or carefully learned [by deep neural networks (DNNs)]. Even more surprisingly, the model sets new records for many classification tasks on the Extended Yale B, AR, and FERET data sets and on MNIST variations. Additional experiments on other public data sets also demonstrate the potential of PCANet to serve as a simple but highly competitive baseline for texture classification and object recognition.

MUTUAL DIFFUSION OF PAIRS OF RARE GASES AT DIFFERENT TEMPERATURES

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

Srivastava, B.N.; Srivastava, K.P.

1959-04-01

The eoefficient of mutual diffusion of the binary gas mixtures Ne--Ar, Ar--Krs and Ne--Kr has been determined at 0, 15, 30s and 45 C. Diffusion is allowed to take place between two diffusion bulbs through a precision capillary tube and samples of gas are withdrawn from one bulb at different times and analyzed by a differential conductivity analyzer. From the experimentally determined values of the diffusion coefficient at different temperatures the unlike interaction parameters for the above gas pairs have been calculated by two different methods on the Lennard-Jones I2:6 model. These values of the force parameters are found tomore » be in good agreement with those obtained from the usual combination rules and also from the thermal diffusion data following the method of Srivastava and Madan. These values are found to reproduce the experimental data on mutual diffusion quite satisfactorily. With Kelvin's method, these data have also been utilized to calculate the self-diffusion coefficient of neon, argons and krypton. (auth)« less

Industrial ion source technology

NASA Technical Reports Server (NTRS)

Kaufman, H. R.; Robinson, R. S.

1978-01-01

An analytical model was developed to describe the development of a coned surface texture with ion bombardment and simultaneous deposition of an impurity. A mathematical model of sputter deposition rate from a beveled target was developed in conjuction with the texturing models to provide an important input to that model. The establishment of a general procedure that will allow the treatment of manay different sputtering configurations is outlined. Calculation of cross sections for energetic binary collisions was extened to Ar, Kr.. and Xe with total cross sections for viscosity and diffusion calculated for the interaction energy range from leV to 1000eV. Physical sputtering and reactive ion etching experiments provided experimental data on the operating limits of a broad beam ion source using CF4 as a working gas to produce reactive species in a sputtering beam. Magnetic clustering effects are observed when Al is seeded with Fe and sputtered with Ar(?) ions. Silicon was textured at a micron scale by using a substrate temperature of 600 C.

Determination of Anthocyanins in Cranberry Fruit and Cranberry Fruit Products by High-Performance Liquid Chromatography with Ultraviolet Detection: Single-Laboratory Validation

PubMed Central

Brown, Paula N.; Shipley, Paul R.

2012-01-01

A single-laboratory validation study was conducted on an HPLC method for the detection and quantification of cyanidin-3-O-galactoside (C3Ga), cyanidin-3-O-glucoside (C3Gl), cyanidin-3-O-arabinoside (C3Ar), peonidin-3-O-galactoside (P3Ga), and peonidin-3-O-arabinoside (P3Ar) in cranberry fruit (Vaccinium macrocarpon Aiton) raw material and finished products. An extraction procedure using a combination of sonication and shaking with acidified methanol was optimized for all five anthocyanins in freeze-dried cranberry fruit and finished products (commercial extract powder, juice, and juice cocktail). Final extract solutions were analyzed by HPLC using a C18 RP column. Calibration curves for all anthocyanin concentrations had correlation coefficients (r2) of ≥99.8%. The method detection limits for C3Ga, C3Gl, C3Ar, P3Ga, and P3Ar were estimated to be 0.018, 0.016, 0.006, 0.013, and 0.011 μg/mL, respectively. Separation was achieved with a chromatographic run time of 35 min using a binary mobile phase with gradient elution. Quantitative determination performed in triplicate on four test materials on each of 3 days (n = 12) resulted in RSDr from 1.77 to 3.31%. Analytical range, as defined by the calibration curves, was 0.57–36.53 μg/mL for C3Ga, 0.15–9.83 μg/mL for C3Gl, 0.28–17.67 μg/mL for C3Ar, 1.01–64.71 μg/mL for P3Ga, and 0.42–27.14 μg/mL for P3Ar. For solid materials prepared by the described method, this translates to 0.06–3.65 mg/g for C3Ga, 0.02–0.98 mg/g for C3Gl, 0.03–1.77 mg/g for C3Ar, 0.10–6.47 mg/g for P3Ga, and 0.04–2.71 mg/g for P3Ar. PMID:21563679

Differential Cross Sections for Ionization of Argon by 1 keV Positron and Electron Impact

NASA Astrophysics Data System (ADS)

Gavin, J.; DuBois, R. D.; de Lucio, O. G.

2014-04-01

Differential information was generated by establishing coincidences and imposing conditions on data recorded for target ions, scattered projectiles, and ejected electrons, as a function of projectile energy loss and scattering angles; in order to describe the interaction between a positron (electron) 1 keV beam and a simple Ar jet. Single ionization triply differential cross section (TDCS) results exhibit two distinct regions (lobes) for which binary (events arising from 2-body interaction) and recoil (events which can only be produced by many-body interactions) interactions are associated. Results indicate that binary events are significantly larger for positron impact, in accordance with theoretical predictions. A similar feature is found for different energy losses and scattering angles. Intensity of the recoil lobe for both projectiles, positron and electron, is observed to depend on the energy loss and scattering angle. Also, it can be noticed that for positron impact the recoil interactions intensity is larger than that observed for electron impact.

Time-resolved Spectroscopy of RS CVn Binaries and dMe Flare Stars

NASA Astrophysics Data System (ADS)

Brown, Alexander

One of the most striking feature of the first two years of EUVE spectroscopy is the frequent occurrence of largescale coronal variability, in the form of stellar flares and slower changes in activity level due to rotational modulation and evolution of active regions. We propose EUVE observations of a set of RS CVn and dMe star binaries, most with short (< 2 days) periods, to investigate the coronal conditions and physical processes associated with this variability. EUVE flare outbursts have mostly been long duration events lasting many satellite orbits and been readily studied using time-resolved spectroscopy. Our targets are the dMe binaries YY Gem, CC Eri and Gliese 2123, and the RS CVn systems EI Eri, AR Psc, and TY Pyx. YY Gem and TY Pyx are eclipsing systems and Deep Survey photometry will be used to investigate the size of the coronal emitting regions. Situated 73 arcmin from YY Gem is Castor (Alpha Gem) another X-ray source that can be observed (and spatially resolved) simultaneously. We shall use the DS lightcurve to guide our time resolved spectral analysis. Changes in the coronal emission measure as a function of temperature and possibly changes in coronal density will be used to constrain magnetic loop models.

Time-Resolved Spectroscopy of Active Binary Stars

NASA Technical Reports Server (NTRS)

Brown, Alexander

2000-01-01

This NASA grant covered EUVE observing and data analysis programs during EUVE Cycle 5 GO observing. The research involved a single Guest Observer project 97-EUVE-061 "Time-Resolved Spectroscopy of Active Binary Stars". The grant provided funding that covered 1.25 months of the PI's salary. The activities undertaken included observation planning and data analysis (both temporal and spectral). This project was awarded 910 ksec of observing time to study seven active binary stars, all but one of which were actually observed. Lambda-And was observed on 1997 Jul 30 - Aug 3 and Aug 7-14 for a total of 297 ksec; these observations showed two large complex flares that were analyzed by Osten & Brown (1999). AR Psc, observed for 350 ksec on 1997 Aug 27 - Sep 13, showed only relatively small flares that were also discussed by Osten & Brown (1999). EUVE observations of El Eri were obtained on 1994 August 24-28, simultaneous with ASCA X-ray spectra. Four flares were detected by EUVE with one of these also observed simultaneously, by ASCA. The other three EUVE observations were of the stars BY Dra (1997 Sep 22-28), V478 Lyr (1998 May 18-27), and sigma Gem (1998 Dec 10-22). The first two stars showed a few small flares. The sigma Gem data shows a beautiful complete flare with a factor of ten peak brightness compared to quiescence. The flare rise and almost all the decay phase are observed. Unfortunately no observations in other spectral regions were obtained for these stars. Analysis of the lambda-And and AR Psc observations is complete and the results were published in Osten & Brown (1999). Analysis of the BY Dra, V478 Lyr and sigma Gem EUVE data is complete and will be published in Osten (2000, in prep.). The El Eri EUV analysis is also completed and the simultaneous EUV/X-ray study will be published in Osten et al. (2000, in prep.). Both these latter papers will be submitted in summer 2000. All these results will form part of Rachel Osten's PhD thesis.

Performance of Low-Density Parity-Check Coded Modulation

NASA Technical Reports Server (NTRS)

Hamkins, Jon

2010-01-01

This paper reports the simulated performance of each of the nine accumulate-repeat-4-jagged-accumulate (AR4JA) low-density parity-check (LDPC) codes [3] when used in conjunction with binary phase-shift-keying (BPSK), quadrature PSK (QPSK), 8-PSK, 16-ary amplitude PSK (16- APSK), and 32-APSK.We also report the performance under various mappings of bits to modulation symbols, 16-APSK and 32-APSK ring scalings, log-likelihood ratio (LLR) approximations, and decoder variations. One of the simple and well-performing LLR approximations can be expressed in a general equation that applies to all of the modulation types.

Ingress observations of the 1980 eclipse of the symbiotic star CI Cyngni

NASA Technical Reports Server (NTRS)

Stencel, R. E.; Michalitsianos, A. G.; Kafatos, M.; Boyarchuk, A. A.

1981-01-01

One of the major results from the IUE may prove to be the knowledge gained by studies of the ultraviolet spectra of symbiotic stars. Symbiotics combine spectral features of a cool M giant like photosphere with strong high excitation emission lines of nebular origin, superposed. The UV spectra are dominated by intense permitted and semiforbidden emission lines and weak continua indicative of hot compact objects and accretion disks. Two symbiotics, AR Pav and CI Cyg are thought to be eclipsing binaries and IUE observations during the 1980 eclipse of CI Cygni are discussed.

Light scattering in gas mixtures - Evidence of fast and slow sound modes

NASA Astrophysics Data System (ADS)

Clouter, M. J.; Luo, H.; Kiefte, H.; Zollweg, J. A.

1990-02-01

Campa and Cohen (1989) have predicted that dilute, binary mixtures of gases with disparate masses should exhibit a (fast) sound mode whose velocity is considerably greater than expected on the basis of conventional hydrodynamic theory, and which should be observable via light-scattering experiments. Effects that are consistent with this prediction were observed in the Brillouin spectra of the H2 + Ar system, but were not detected for the case of CH4 + SF6. Results for the SF6 + H2 mixture demonstrate the existence of an analogous slow-mode contribution to the spectrum.

Molecular Authentication of the Traditional Medicinal Plant "Lakshman Booti" (Smithia conferta Sm.) and Its Adulterants through DNA Barcoding.

PubMed

Umdale, Suraj D; Kshirsagar, Parthraj R; Lekhak, Manoj M; Gaikwad, Nikhil B

2017-07-01

Smithia conferta Sm. is an annual herb widely used in Indian traditional medical practice and commonly known as "Lakshman booti" in Sanskrit. Morphological resemblance among the species of genus Smithia Aiton . leads to inaccurate identification and adulteration. This causes inconsistent therapeutic effects and also affects the quality of herbal medicine. This study aimed to generate potential barcode for authentication of S. conferta and its adulterants through DNA barcoding technique. Genomic DNA extracted from S. conferta and its adulterants was used as templates for polymerase chain reaction amplification of the barcoding regions. The amplicons were directed for sequencing, and species identification was conducted using BLASTn and unweighted pair-group method with arithmetic mean trees. In addition, the secondary structures of internal transcribed spacer (ITS) 2 region were predicted. The nucleotide sequence of ITS provides species-specific single nucleotide polymorphisms and sequence divergence (22%) than psb A- trn H (10.9%) and rbc L (3.1%) sequences. The ITS barcode indicates that S. conferta and Smithia sensitiva are closely related compared to other species. ITS is the most applicable barcode for molecular authentication of S. conferta , and further chloroplast barcodes should be tested for phylogenetic analysis of genus Smithia. The present investigation is the first effort of utilization of DNA barcode for molecular authentication of S. conferta and its adulterants. Also, this study expanded the application of the ITS2 sequence data in the authentication. The ITS has been proved as a potential and reliable candidate barcode for the authentication of S. conferta . Abbreviations used: BLASTn: Basic Local Alignment Search Tool for Nucleotide; MEGA: Molecular Evolutionary Genetic Analysis; EMBL: European Molecular Biology Laboratory; psb A- trn H: Photosystem II protein D1- stuctural RNA: His tRNA gene; rbcL: Ribulose 1,5 bi-phosphate carboxylase/oxygenase large subunit gene.

Green binary and phase shifting mask

NASA Astrophysics Data System (ADS)

Shy, S. L.; Hong, Chao-Sin; Wu, Cheng-San; Chen, S. J.; Wu, Hung-Yu; Ting, Yung-Chiang

2009-12-01

SixNy/Ni thin film green mask blanks were developed , and are now going to be used to replace general chromium film used for binary mask as well as to replace molydium silicide embedded material for AttPSM for I-line (365 nm), KrF (248 nm), ArF (193 nm) and Contact/Proximity lithography. A bilayer structure of a 1 nm thick opaque, conductive nickel layer and a SixNy layer is proposed for binary and phase-shifting mask. With the good controlling of plasma CVD of SixNy under silane (50 sccm), ammonia (5 sccm) and nitrogen (100 sccm), the pressure is 250 mTorr. and RF frequency 13.56 MHz and power 50 W. SixNy has enough deposition latitude to meet the requirements as an embedded layer for required phase shift 180 degree, and the T% in 193, 248 and 365 nm can be adjusted between 2% to 20% for binary and phase shifting mask usage. Ni can be deposited by E-gun, its sheet resistance Rs is less than 1.435 kΩ/square. Jeol e-beam system and I-line stepper are used to evaluate these thin film green mask blanks, feature size less than 200 nm half pitch pattern and 0.558 μm pitch contact hole can be printed. Transmission spectrums of various thickness of SixNy film are inspected by using UV spectrometer and FTIR. Optical constants of the SixNy film are measured by n & k meter and surface roughness is inspected by using Atomic Force Microscope (AFM).

A Model for AR Scorpii: Emission from Relativistic Electrons Trapped by Closed Magnetic Field Lines of Magnetic White Dwarfs

NASA Astrophysics Data System (ADS)

Takata, J.; Yang, H.; Cheng, K. S.

2017-12-01

AR Scorpii is an intermediate polar binary system composed of a magnetic white dwarf (WD) and an M-type star and shows nonthermal, pulsed, and highly linearly polarized emission. The radio/optical emission modulates with the WD’s spin and shows the double-peak structure in the light curves. In this paper, we discuss a possible scenario for the radiation mechanism of AR Scorpii. The magnetic interaction on the surface of the companion star produces an outflow from the companion star, the heating of the companion star surface, and the acceleration of electrons to a relativistic energy. The accelerated electrons, whose typical Lorentz factor is ∼50–100, from the companion star move along the magnetic field lines toward the WD surface. The electrons injected with the pitch angle of \\sin {θ }p,0> 0.05 are subject to the magnetic mirror effect and are trapped in the closed magnetic field line region. We find that the emission from the first magnetic mirror points mainly contributes to the observed pulsed emission and the formation of the double-peak structure in the light curve. For the inclined rotator, the pulse peak in the calculated light curve shifts the position in the spin phase, and a Fourier analysis exhibits a beat frequency feature, which are consistent with the optical/UV observations. The pulse profile also evolves with the orbital phase owing to the effect of the viewing geometry. The model also interprets the global features of the observed spectral energy distribution in radio to X-ray energy bands. We also discuss the curvature radiation and the inverse-Compton scattering process in the outer gap accelerator of the WD in AR Scorpii and the possibility of the detection by future high-energy missions.

Infrared Spectroscopy of Symbiotic Stars. XI. Orbits for Southern S-type Systems: Hen 3-461, SY Mus, Hen 3-828, AND AR Pav

NASA Astrophysics Data System (ADS)

Fekel, Francis C.; Hinkle, Kenneth H.; Joyce, Richard R.; Wood, Peter R.

2017-01-01

Employing new infrared radial velocities, we have computed spectroscopic orbits of the cool giants in four southern S-type symbiotic systems. The orbits for two of the systems, Hen 3-461 and Hen 3-828, have been determined for the first time, while orbits of the other two, SY Mus and AR Pav, have previously been determined. For the latter two systems, we compare our results with those in the literature. The low mass of the secondary of SY Mus suggests that it has gone through a common envelope phase. Hen 3-461 has an orbital period of 2271 days, one of the longest currently known for S-type symbiotic systems. That period is very different from the orbital period proposed previously from its photometric variations. The other three binaries have periods between 600 and 700 day, values that are typical for S-type symbiotic orbits. Basic properties of the M giant components and the distance to each system are determined.

Infrared observations of RS CVn stars

NASA Technical Reports Server (NTRS)

Berriman, G.; De Campli, W. M.; Werner, M. W.; Hatchett, S. P.

1983-01-01

The paper presents infrared photometry of the RS CVn binary stars AR Lac (1.2-10 microns) and MM Her (1.2-3.5 microns) as they egressed from their primary and secondary eclipses; of the eclipsing systems RS CVn and Z Her at maximum light (1.2-10 microns) and of the non-eclipsing systems UX Ari and HR 1099 (1.2-10 microns). An analysis of these and published V data based on flux ratio diagrams (linear analogues of color-color diagrams) shows that G and K stars supply the infrared light of these systems. In AR Lac, the combined light of a G5-K0 subgiant and either a late F dwarf or an early F subgiant can account for the observed visual and infrared light curves. None of these systems shows infrared emission from circumstellar matter. This result is simply understood: dust grains would not be expected to form in the physical conditions surrounding the subgiant, and the corona and chromosphere (whose properties have been deduced from spectroscopic X-ray observations) should not produce appreciable infrared emission.

Mapping and Modeling the Extended Winds of the Massive Interacting Binary, Eta Carinae

NASA Technical Reports Server (NTRS)

Gull, Ted

2010-01-01

The combination HST/STIS high spatial and moderate spectral resolutions have revealed the massive interacting wind structure of Eta Carinae by forbidden lines of singly and doubly ionized elements. Throughout the 5.54-year period, lines of Fe++, Ne++, Ar++, S++ and N+ reveal the interacting wind structures, near critical electron densities of 10(exp 5) to 3 x 10(exp 7)cu cm, photoionized by the hot secondary, Eta Car B, Lines of Fe+ and Ni+ trace the denser (>10(exp 7)cu cm. less-ionized (< 8 eV) primary wind of Eta Car A as it wraps around the interacting binary stars. For 5 years of the 5.54 year period, the FUV radiation from Eta Car B escapes the orbital region, ionizing the boundaries of the expanding wind structures. But for three to six months, Eta Car B plunges into the primary wind approaching to within 1 to 2 AU, leading to cutoff of FUV and X-ray fluxes. The interacting wind structure, resolved out to 0.8", drops io ionization and then rebuilds as Eta Car B emerges from the primary wind envelope. Solid Particle Hydrodynamical(SPH) models have been developed extending out to 2000 AU and adapted to include FUV radiation effects of the winds. In turn, synthetic spectroimages of selected forbidden lines have been constructed and compared to the spectroimages recorded by the HST/STIS throughout 1998.0 to 2004.3, extending across the 1998 and 2003.5 minima. By this method, we show that the orbital axis of the binary system must bc within 15 degrees of the Homunculus axis of symmetry and that periastron occurs with Eta Car B passing on the far side of Eta Car B. This result ties the current binary orbit with the bipolar ejection with intervening skirt and leads to implications that the binary system influenced the mass ejection of the l840s and the lesser ejection of the 1890s.

Thermodynamic modelling of the C-U and B-U binary systems

NASA Astrophysics Data System (ADS)

Chevalier, P. Y.; Fischer, E.

2001-02-01

The thermodynamic modelling of the carbon-uranium (C-U) and boron-uranium (B-U) binary systems is being performed in the framework of the development of a thermodynamic database for nuclear materials, for increasing the basic knowledge of key phenomena which may occur in the event of a severe accident in a nuclear power plant. Applications are foreseen in the nuclear safety field to the physico-chemical interaction modelling, on the one hand the in-vessel core degradation producing the corium (fuel, zircaloy, steel, control rods) and on the other hand the ex-vessel molten corium-concrete interaction (MCCI). The key O-U-Zr ternary system, previously modelled, allows us to describe the first interaction of the fuel with zircaloy cladding. Then, the three binary systems Fe-U, Cr-U and Ni-U were modelled as a preliminary work for modelling the O-U-Zr-Fe-Cr-Ni multicomponent system, allowing us to introduce the steel components in the corium. In the existing database (TDBCR, thermodynamic data base for corium), Ag and In were introduced for modelling AIC (silver-indium-cadmium) control rods which are used in French pressurized water reactors (PWR). Elsewhere, B 4C is also used for control rods. That is why it was agreed to extend in the next years the database with two new components, B and C. Such a work needs the thermodynamic modelling of all the binary and pseudo-binary sub-systems resulting from the combination of B, B 2O 3 and C with the major components of TDBCR, O-U-Zr-Fe-Cr-Ni-Ag-In-Ba-La-Ru-Sr-Al-Ca-Mg-Si + Ar-H. The critical assessment of the very numerous experimental information available for the C-U and B-U binary systems was performed by using a classical optimization procedure and the Scientific Group Thermodata Europe (SGTE). New optimized Gibbs energy parameters are given, and comparisons between calculated and experimental equilibrium phase diagrams or thermodynamic properties are presented. The self-consistency obtained is quite satisfactory.

Sex steroid-related genes and male-to-female transsexualism.

PubMed

Henningsson, Susanne; Westberg, Lars; Nilsson, Staffan; Lundström, Bengt; Ekselius, Lisa; Bodlund, Owe; Lindström, Eva; Hellstrand, Monika; Rosmond, Roland; Eriksson, Elias; Landén, Mikael

2005-08-01

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and--after aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

In situ monitoring of atomic layer controlled pore reduction in alumina tubular membranes using sequential surface reactions

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

Berland, B.S.; Gartland, I.P.; Ott, A.W.

1998-12-01

The pore diameter in alumina tubular membranes with an initial diameter of 50 {angstrom} was systematically reduced using the atomic layer controlled deposition of Al{sub 2}O{sub 3}. The Al{sub 2}O{sub 3} was deposited using sequential exposures of Al(CH{sub 3}){sub 3} (trimethylaluminum, TMA) and H{sub 2}O in an ABAB... binary reaction sequence. The pore diameter reduction was monitored using in situ N{sub 2} and Ar conductance measurements. The conductance, C = Q/{Delta}P, was measured using a mass flow controller to define a constant gas throughput, Q, and a pair of capacitance manometers to monitor the transmembrane pressure drop, {Delta}P. Conductance measurementsmore » were periodically obtained at 298 K as a function of AB binary reaction cycles. These conductance measurements were consistent with a pore diameter reduction from 50 {angstrom} to {approximately}5--10 {angstrom} at a rate of {approximately}2.5 {angstrom} for each AB cycle. Conductance measurements were also performed during the Al{sub 2}O{sub 3} deposition at 500 K after each half-reaction in the binary reaction sequence. These in situ conductance measurements demonstrate that the pore diameters in mesoporous membranes can be reduced to molecular dimensions with atomic layer control using sequential surface reactions. Poe diameters can be tailored for specific applications by varying the number of AB cycles and changing the nature of the terminating surface functional groups.« less

Development of ultrafine Ti-Fe-Sn in-situ composite with enhanced plasticity

NASA Astrophysics Data System (ADS)

Mondal, B.; Samal, S.; Biswas, K.; Govind

2012-01-01

The present investigation is aimed at developing ultrafine eutectic/dendrite Ti-Fe-Sn in-situ composite with balanced combination of strength and plasticity. It also studies the microstructure evolution in the series of hypereutectic Ti-Fe-Sn ternary alloys. Sn concentration of these alloys has been varied from 0 - 10 atom% in the binary alloy (Ti71Fe29) keeping the Ti concentration fixed. These alloys have been prepared by arc melting under an Ar atmosphere on a water-cooled Cu hearth, which are subsequently suction cast in a split Cu-mold under an Ar atmosphere. Detailed X-ray diffraction (XRD) study shows the presence of TiFe, β-Ti, and Ti3Sn phases. The SEM micrographs reveal that the microstructures consist of fine scale eutectic matrix (β-Ti and TiFe) with primary dendrite phases (TiFe and/or Ti3Sn) depending on concentration of Sn. α -Ti forms as a eutectoid reaction product of β-Ti. The room temperature uniaxial compressive test reveals simultaneous improvement in the strength (1942 MPa) and plasticity (13.1 %) for Ti71Fe26Sn3 ternary alloy. The fracture surface indicates a ductile mode of fracture for the alloy.

Search for ternary fission of chromium-48

NASA Astrophysics Data System (ADS)

Dummer, Andrew K.

1999-07-01

Both alpha cluster model calculations and macroscopic energy calculations that allow for a double-neck shape of the compound nucleus suggest the possibility of a novel three 16O, chain-like configuration in 48 Cr. Such a configuration might lead to an enhanced cross section for three-16O breakup. To explore this possibility, the three-body exit channels for the 36Ar + 12C reaction at a beam energy of 210 MeV have been studied. The cross section for 16O + 16O + 16O breakup has been deduced and has been found to be in excess of what would be expected to result from a sequential binary fission process. However, the observation of a similarly enhanced 12C + 16O + 20Ne breakup cross section suggests that the observed 16O + 16O + 16O yields might still be associated with a statistical fission process. The results are discussed in the context of the fission of light nuclear systems and a simple cluster model calculation. This latter, ``Harvey model'' calculation suggests a possible inhibition of the formation of a three- 16O chain configuration from the 36Ar + 12C entrance channel. A further measurement using the 20Ne + 28Si-entrance channel is suggested.

Line Identifications in the Far Ultraviolet Spectrum of the Eclipsing Binary System 31 Cygni

NASA Astrophysics Data System (ADS)

Hagen Bauer, Wendy; Bennett, P. D.

2011-05-01

The eclipsing binary system 31 Cygni (K4 Ib + B3 V) was observed at several phases with the Far Ultraviolet Spectrosocopic Explorer (FUSE) satellite. During total eclipse, a rich emission spectrum was observed, produced by scattering of hot star photons in the extended wind of the K supergiant. The system was observed during deep chromospheric eclipse, and 2.5 months after total eclipse ended. We present an atlas of line identifications in these spectra. During total eclipse, emission features from C II , C III, N I, N II, N III, O I, Si II, P II, P III, S II, S III, Ar I, Cr III, Fe II, Fe III, and Ni II were detected. The strongest emission features arise from N II. These lines appear strongly in absorption during chromospheric eclipse, and even 2.5 months after total eclipse, the absorption bottoms out on the underlying emission seen during total eclipse. The second strongest features in the emission spectrum arise from Fe III. Any chromospheric Fe III absorption is buried within strong chromospheric absorption from other species, mainly Fe II. The emission profiles of most of the doubly-ionized species are red-shifted relative to the systemic velocity, with asymmetric profiles with a steeper long-wavelength edge. Emission profiles from singly-ionized species tend to be more symmetric and centered near the systemic velocity. In deep chromospheric eclipse, absorption features are seen from neutral and singly-ionized species, arising from lower levels up to 3 eV. Many strong chromospheric features are doubled in the observation obtained during egress from eclipse. The 31 Cygni spectrum taken 2.5 months after total eclipse ended ws compared to single-star B spectra from the FUSE archives. There was still some additional chromospheric absorption from strong low-excitation Fe II, O I and Ar I.

Comparison of methods for estimating the attributable risk in the context of survival analysis.

PubMed

Gassama, Malamine; Bénichou, Jacques; Dartois, Laureen; Thiébaut, Anne C M

2017-01-23

The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points. Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort. In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears appropriate.

Transport properties in mixtures involving carbon dioxide at low and moderate density: test of several intermolecular potential energies and comparison with experiment

NASA Astrophysics Data System (ADS)

Moghadasi, Jalil; Yousefi, Fakhri; Papari, Mohammad Mehdi; Faghihi, Mohammad Ali; Mohsenipour, Ali Asghar

2009-09-01

It is the purpose of this paper to extract unlike intermolecular potential energies of five carbon dioxide-based binary gas mixtures including CO2-He, CO2-Ne, CO2-Ar, CO2-Kr, and CO2-Xe from viscosity data and compare the calculated potentials with other models potential energy reported in literature. Then, dilute transport properties consisting of viscosity, diffusion coefficient, thermal diffusion factor, and thermal conductivity of aforementioned mixtures are calculated from the calculated potential energies and compared with literature data. Rather accurate correlations for the viscosity coefficient of afore-cited mixtures embracing the temperature range 200 K < T < 3273.15 K is reproduced from the present unlike intermolecular potentials energy. Our estimated accuracies for the viscosity are to within ±2%. In addition, the calculated potential energies are used to present smooth correlations for other transport properties. The accuracies of the binary diffusion coefficients are of the order of ±3%. Finally, the unlike interaction energy and the calculated low density viscosity have been employed to calculate high density viscosities using Vesovic-Wakeham method.

Sphericalization of the potential of interaction of anisotropic molecules with spherical particles

NASA Astrophysics Data System (ADS)

Fernández-Prini, R.; Japas, María L.

1986-09-01

The possibility of employing sphericalized intermolecular potentials to describe the interactions between nonpolar anisotropic molecules (CCl4 and benzene) with spherical nonpolar molecules (Ar, Xe, and CH4) has been tested for binary systems having liquid- and gas-like densities. Median and RAM sphericalization procedures have been used and their capacity to account for the experimental values of cross second virial coefficients and Henry's constants are compared. It is shown that the median sphericalized potentials, which are temperature and density independent, give a fairly good description of the data which is better than that provided by RAM potentials. The possibility of accounting correctly for the change of properties when the relative size of the interacting partners changes (e.g., conformal systems) is noteworthy.

Repellent activity of catmint, Nepeta cataria, and iridoid nepetalactone isomers against Afro-tropical mosquitoes, ixodid ticks and red poultry mites.

PubMed

Birkett, Michael A; Hassanali, Ahmed; Hoglund, Solveig; Pettersson, Jan; Pickett, John A

2011-01-01

The repellent activity of the essential oil of the catmint plant, Nepeta cataria (Lamiaceae), and the main iridoid compounds (4aS,7S,7aR) and (4aS,7S,7aS)-nepetalactone, was assessed against (i) major Afro-tropical pathogen vector mosquitoes, i.e. the malaria mosquito, Anopheles gambiae s.s. and the Southern house mosquito, Culex quinquefasciatus, using a World Health Organisation (WHO)-approved topical application bioassay (ii) the brown ear tick, Rhipicephalus appendiculatus, using a climbing repellency assay, and (iii) the red poultry mite, Dermanyssus gallinae, using field trapping experiments. Gas chromatography (GC) and coupled GC-mass spectrometry (GC-MS) analysis of two N. cataria chemotypes (A and B) used in the repellency assays showed that (4aS,7S,7aR) and (4aS,7S,7aS)-nepetalactone were present in different proportions, with one of the oils (from chemotype A) being dominated by the (4aS,7S,7aR) isomer (91.95% by GC), and the other oil (from chemotype B) containing the two (4aS,7S,7aR) and (4aS,7S,7aS) isomers in 16.98% and 69.83% (by GC), respectively. The sesquiterpene hydrocarbon (E)-(1R,9S)-caryophyllene was identified as the only other major component in the oils (8.05% and 13.19% by GC, respectively). Using the topical application bioassay, the oils showed high repellent activity (chemotype A RD(50)=0.081 mg cm(-2) and chemotype B RD(50)=0.091 mg cm(-2)) for An. gambiae comparable with the synthetic repellent DEET (RD(50)=0.12 mg cm(-2)), whilst for Cx. quinquefasciatus, lower repellent activity was recorded (chemotype A RD(50)=0.34 mg cm(-2) and chemotype B RD(50)=0.074 mg cm(-2)). Further repellency testing against An. gambiae using the purified (4aS,7S,7aR) and (4aS,7S,7aS)-nepetalactone isomers revealed overall lower repellent activity, compared to the chemotype A and B oils. Testing of binary mixtures of the (4aS,7S,7aR) and (4aS,7S,7aS) isomers across a range of ratios, but all at the same overall dose (0.1 mg), revealed not only a synergistic effect between the two, but also a surprising ratio-dependent effect, with lower activity for the pure isomers and equivalent or near-equivalent mixtures, but higher activity for non-equivalent ratios. Furthermore, a binary mixture of (4aS,7S,7aR) and (4aS,7S,7aS) isomers, in a ratio equivalent to that found in chemotype B oil, was less repellent than the oil itself, when tested at two doses equivalent to 0.1 and 0.01 mg chemotype B oil. The three-component blend including (E)-(1R,9S)-caryophyllene at the level found in chemotype B oil had the same activity as chemotype B oil. In a tick climbing repellency assay using R. appendiculatus, the oils showed high repellent activity comparable with data for other repellent essential oils (chemotype A RD(50)=0.005 mg and chemotype B RD(50)=0.0012 mg). In field trapping assays with D. gallinae, addition of the chemotype A and B oils, and a combination of the two, to traps pre-conditioned with D. gallinae, all resulted in a significant reduction of D. gallinae trap capture. In summary, these data suggest that although the nepetalactone isomers have the potential to be used in human and livestock protection against major pathogen vectors, intact, i.e. unfractionated, Nepeta spp. oils offer potentially greater protection, due to the presence of both nepetalactone isomers and other components such as (E)-(1R,9S)-caryophyllene. Copyright © 2010 Elsevier Ltd. All rights reserved.

Physical processes in directed ion beam sputtering. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Robinson, R. S.

1979-01-01

The general operation of a discharge chamber for the production of ions is described. A model is presented for the magnetic containment of both primary and secondary or Maxwellian electrons in the discharge plasma. Cross sections were calculated for energy and momentum transfer in binary collisions between like pairs of Ar, Kr, and Xe atoms in the energy range from about 1 eV to 1000 eV. These calculations were made from available pair interaction potentials using a classical model. Experimental data from the literature were fit to a theoretical expression for the Ar resonance charge exchange cross section over the same energy range. A model was developed that describes the processes of conical texturing of a surface due to simultaneous directed ion beam etching and sputter deposition of an impurity material. This model accurately predicts both a minimum temperature for texturing to take place and the variation of cone density with temperature. It also provides the correct order of magnitude of cone separation. It was predicted from the model, and subsequently verified experimentally, that a high sputter yield material could serve as a seed for coning of a lower sputter yield substrate. Seeding geometries and seed deposition rates were studied to obtain an important input to the theoretical texturing model.

Normal mode analysis on the relaxation of an excited nitromethane molecule in argon bath

NASA Astrophysics Data System (ADS)

Rivera-Rivera, Luis; Wagner, Albert

In our previous work [J. Chem. Phys. 142, 014303 (2015)] classical molecular dynamics simulations followed in an Ar bath the relaxation of nitromethane (CH3NO2) instantaneously excited by statistically distributing 50 kcal/mol among all its internal degrees of freedom. The 300 K Ar bath was at pressures of 10 to 400 atm, a range spanning the breakdown of the isolated binary collision approximation. Both rotational and vibrational energies exhibit multi-exponential decay. This study explores mode-specific mechanisms at work in the decay process. With the separation of rotation and vibration developed by Rhee and Kim [J. Chem. Phys. 107, 1394 (1997)], one can show that the vibrational kinetic energy decomposes only into vibrational normal modes while the rotational and Coriolis energies decompose into both vibrational and rotational normal modes. Then the saved CH3NO2 positions and momenta can be converted into mode-specific energies whose decay over 1000 ps can be monitored. The results identify vibrational and rotational modes that promote/resist energy lost and drive multi-exponential behavior. Increasing pressure can be shown to increasingly interfere with post-collision IVR. The work was supported by the U.S. Department of Energy, Office of Science, Chemical Sciences, Geosciences, and Biosciences Division.

Simulation of redistributive and erosive effects in a-Si under Ar+ irradiation

NASA Astrophysics Data System (ADS)

Lopez-Cazalilla, A.; Ilinov, A.; Bukonte, L.; Nordlund, K.; Djurabekova, F.; Norris, S.; Perkinson, J. C.

2018-01-01

Ion beams are frequently used in industry for composition control of semiconducting materials as well as for surface processing and thin films deposition. Under certain conditions, low- and medium energy ions at high fluences can produce nanoripples and quantum dots on the irradiated surfaces. In the present work, we focus our attention on the study of irradiation of amorphous silicon (a-Si) target with 250 eV and 1 keV Ar+ ions under different angles, taking into special consideration angles close to the grazing incidence. We use the molecular dynamics (MD) method to investigate how much the cumulative displacement of atoms due to the simulated ion bombardment contribute to the patterning effect. The MD results are subsequently analysed using a numerical module Pycraters that allows the prediction of the rippling effect. Ripple wavelengths estimated with Pycraters are then compared with the experimental observations, as well as with the results obtained by using the binary collisions approximation (BCA) method. The wavelength estimation based on the MD results demonstrates a better agreement with the experimental values. In the framework of the utilized analytical model, it can be mainly attributed to the fact that the BCA ignores low energy atomic interactions, which, however, provide an important contribution to the displacement of atoms following an ion impact.

Effects of Processing Variables on Tantalum Nitride by Reactive-Ion-Assisted Magnetron Sputtering Deposition

NASA Astrophysics Data System (ADS)

Wei, Chao‑Tsang; Shieh, Han‑Ping D.

2006-08-01

The binary compound tantalum nitride (TaN) and ternary compounds tantalum tungsten nitrides (Ta1-xWxNy) exhibit interesting properties such as high melting point, high hardness, and chemical inertness. Such nitrides were deposited on a tungsten carbide (WC) die and silicon wafers by ion-beam-sputter evaporation of the respective metal under nitrogen ion-assisted deposition (IAD). The effects of N2/Ar flux ratio, post annealing, ion-assisted deposition, deposition rate, and W doping in coating processing variables on hardness, load critical scratching, oxidation resistance, stress and surface roughness were investigated. The optimum N2/Ar flux ratios in view of the hardness and critical load of TaN and Ta1-xWxNy films were ranged from 0.9 to 1.0. Doping W into TaN to form Ta1-xWxNy films led significant increases in hardness, critical load, oxidation resistance, and reduced surface roughness. The optimum doping ratio was [W/(W+Ta)]=0.85. From the deposition rate and IAD experiments, the stress in the films is mainly contributed by sputtering atoms. The lower deposition rate at a high N2/Ar flux ratio resulted in a higher compressive stress. A high compressive residual stress accounts for a high hardness. The relatively high compressive stress was attributed primarily to peening by atoms, ions and electrons during film growth, the Ta1-xWxNy films showed excellent hardness and strength against a high temperature, and sticking phenomena can essentially be avoided through their use. Ta1-xWxNy films showed better performance than the TaN film in terms of mechanical properties and oxidation resistance.

How Expanded Ionospheres of Hot Jupiters Can Prevent Escape of Radio Emission Generated by the Cyclotron Maser Instability

NASA Astrophysics Data System (ADS)

Weber, Christof; Lammer, Helmut; Shaikhislamov, Ildar F.; Erkaev, Nikolai; Chadney, Joshua M.; Khodachenko, Maxim L.; Grießmeier, Jean-Mathias; Rucker, Helmut O.; Vocks, Christian; Macher, Wolfgang; Odert, Petra; Kislyakova, Kristina G.

2017-04-01

We present a study of the plasma conditions in the atmospheres of the Hot Jupiters HD 209458b and HD 189733b and for an HD 209458b-like planet at orbit locations between 0.2-1 AU around a Sun-like star. We discuss how these conditions influence the radio emission we expect from their planetary magnetospheres. We find that the environmental conditions for the cyclotron maser instability (CMI), the process which is responsible for the generation of radio waves at magnetic planets in the solar system, most likely will not operate at Hot Jupiters. The reason for that is that hydrodynamically expanding atmospheres possess extended ionospheres whose plasma densities within the magnetosphere are so large that the plasma frequency is much higher than the cyclotron frequency, which contradicts the necessary condition for the production of radio emission and prevents the escape of radio waves from close-in extrasolar planets at distances <0.05 AU from a Sun-like host star. The upper atmosphere structure of Hot Jupiters around stars similar to the Sun changes between 0.2 and 0.5 AU from the hydrodynamic to a hydrostatic regime and this results in conditions similar to solar system planets with a region of depleted plasma between the exobase and the magnetopause where the plasma frequency can be lower than the cyclotron frequency. In such an environment a beam of highly energetic electrons accelerated along the field lines towards the planet can produce radio emission. However, even if the CMI could operate the extended ionospheres of Hot Jupiters are too dense to let the radio emission escape from the planets. We also investigate the possible radio emission of the Hot Jupiter Tau Bootis b by placing it at different orbital distances from the host star, i.e. 0.1 and 0.2 AU. In particular we check if the atmosphere of Tau Bootis b at 0.046 AU is in the hydrostatic or in the hydrodynamic regime. If it is in the hydrodynamic regime it's ionosphere is extended and will constitute an obstacle for possibly generated radio waves or the generation via the Cyclotron Maser Instability (CMI) might even be prevented completely. Furthermore we investigate at which orbital location the atmosphere undergoes the transformation from hydrodynamic to hydrostatic, i.e. the transformation to more favourable conditions for the CMI.

Modification of the Sandwich Estimator in Generalized Estimating Equations with Correlated Binary Outcomes in Rare Event and Small Sample Settings

PubMed Central

Rogers, Paul; Stoner, Julie

2016-01-01

Regression models for correlated binary outcomes are commonly fit using a Generalized Estimating Equations (GEE) methodology. GEE uses the Liang and Zeger sandwich estimator to produce unbiased standard error estimators for regression coefficients in large sample settings even when the covariance structure is misspecified. The sandwich estimator performs optimally in balanced designs when the number of participants is large, and there are few repeated measurements. The sandwich estimator is not without drawbacks; its asymptotic properties do not hold in small sample settings. In these situations, the sandwich estimator is biased downwards, underestimating the variances. In this project, a modified form for the sandwich estimator is proposed to correct this deficiency. The performance of this new sandwich estimator is compared to the traditional Liang and Zeger estimator as well as alternative forms proposed by Morel, Pan and Mancl and DeRouen. The performance of each estimator was assessed with 95% coverage probabilities for the regression coefficient estimators using simulated data under various combinations of sample sizes and outcome prevalence values with an Independence (IND), Autoregressive (AR) and Compound Symmetry (CS) correlation structure. This research is motivated by investigations involving rare-event outcomes in aviation data. PMID:26998504

The Spatially-resolved Interacting Winds of Eta Carinae: Implications on the Orbit Orientation

NASA Technical Reports Server (NTRS)

Gull, Theodore R.; Nielsen, K.E.; Corcoran, M.; Hamaguchi, K.; Madura, T.; Russell, C.; Hillier, D.J.; Owocki. S.; Okazaki, A.T.

2010-01-01

Medium-dispersion long slit spectra, recorded by HST/STIS (R=8000, Theta=0.l"), resolve the extended wind-wind interaction region of the massive binary, Eta Carinae. During the high state, extending for about five years of the 5.54-year binary period, lines of [N II], [Fe III], [S III], [Ar III] and [Ne III] extend outwards to 0.4" with a velocity range of -500 to +200 km/s. By comparison, lines of [Fe II] and [Ni II] extend to 0.7" with a velocity range of -500 to +500 km/s. During the high state, driven by the lesser wind of Eta Car B and photo-ionized by the FUV of Eta Car B, the high excitation lines originate in or near the outer ballistic portions of the wind-wind interaction region. The lower excitation lines ([Fe II] and [Ni II D originate from the boundary regions of the dominating wind of Eta Car A. As the binary system has an eccentricity exceeding 0.9, the two stars approach quite close across the periastron, estimated to be within 1 to 2 AU. As a result, Eta Car B moves into the primary wind structure, cutting off the FUV supporting the ionization of the high state lines. Forbidden emission lines of the doubly-ionized species disappear, He II 4686 drops along with the collapse of the X-ray flux. This behavior is understood through the 3-D models of A. Okazaki and of E. R. Parkin and Pittard. Discussion will address the orbit orientation relative to the geometry of the Homunculus, ejected by Eta Carinae in the 1840s.

The Spatially-resolved Interacting Winds of Eta Carinae: Implications on the Orbit Orientation

NASA Astrophysics Data System (ADS)

Gull, Theodore R.; Nielsen, K. E.; Corcoran, M.; Hamaguchi, K.; Madura, T.; Russell, C.; Hillier, D. J.; Owocki, S.; Okazaki, A. T.

2010-01-01

Medium-dispersion long slit spectra, recorded by HST/STIS (R=8000, Theta=0.1"), resolve the extended wind-wind interaction region of the massive binary, Eta Carinae. During the high state, extending for about five years of the 5.54-year binary period, lines of [N II], [Fe III], [S III], [Ar III] and [Ne III] extend outwards to 0.4" with a velocity range of -500 to +200 km/s. By comparison, lines of [Fe II] and [Ni II] extend to 0.7" with a velocity range of -500 to +500 km/s. During the high state, driven by the lesser wind of Eta Car B and photo-ionized by the FUV of Eta Car B, the high excitation lines originate in or near the outer ballistic portions of the wind-wind interaction region. The lower excitation lines ([Fe II] and [Ni II]) originate from the boundary regions of the dominating wind of Eta Car A. As the binary system has an eccentricity exceeding 0.9, the two stars approach quite close across the periastron, estimated to be within 1 to 2 AU. As a result, Eta Car B moves into the primary wind structure, cutting off the FUV supporting the ionization of the high state lines. Forbidden emission lines of the doubly-ionized species disappear, He II 4686 drops along with the collapse of the X-ray flux. This behavior is understood through the 3-D models of A. Okazaki and of E. R. Parkin and Pittard. Discussion will address the orbit orientation relative to the geometry of the Homunculus, ejected by Eta Carinae in the 1840s.

The Stokes-Einstein relationship and the levitation effect: size-dependent diffusion maximum in dense fluids and close-packed disordered solids.

PubMed

Ghorai, Pradip Kr; Yashonath, S

2005-03-31

We report a molecular dynamics study of a binary mixture consisting of a large (host) particle and a smaller (guest) particle whose radius is varied over a range. These simulations investigate the possible existence of a diffusion anomaly or levitation effect in dense fluids, previously seen for guest molecules diffusing within porous solids. The voids in the larger component have been characterized in terms of void and neck distributions by means of Voronoi polyhedral analysis. Four different mixtures with differing ratios of guest to host diffusivities (D) have been studied. The results suggest that the diffusion anomaly is seen in both close-packed solids with disorder and dense fluids. In the latter, the void network is constantly and dynamically changing and possesses a considerable degree of disorder. The two regimes, viz., the linear regime (LR) and the anomalous regime (AR), found for porous solids are shown to exist for a dense medium as well. The linear regime is characterized by D(g) proportional to 1/sigma(gg)(2), where sigma(gg) is the diameter of the guest. The anomalous regime exhibits a maximum in D up to rather high temperatures (T = 1.663), even though in porous solids the maximum disappears at higher temperatures. In agreement with previous studies on porous solids, a particle in the AR is associated with lower activation energy, lower friction, and less backscattering in the velocity autocorrelation function when compared to a particle in the LR. Wavevector dependent self-diffusivity, Delta, and decay of the intermediate scattering function, F(s)(k, t), exhibit contrasting behaviors for the LR and AR. For LR, Delta exhibits a minimum at values of k at which there are spatial correlations in S(k) while a smooth decrease with k is seen for AR. For LR, F(s)(k, t) shows a biexponential decay corresponding to two different time scales of motion. Probably, the fast decay is associated with motion within the first shell of solvent neighbors and the slow decay with motion past these shells. For AR, a single-exponential decay is seen. The results indicate a breakdown of the Stokes-Einstein (SE) relationship. The relevant quantity that determines the validity of the SE relationship is the levitation parameter which is indirectly related to the solute/solvent radius ratio and not either the size of the solute or the solvent alone.

Digging in the coronal graveyard - A Rosat observation of the red giant Arcturus

NASA Technical Reports Server (NTRS)

Ayres, Thomas R.; Fleming, Thomas A.; Schmitt, Juergen H. M. M.

1991-01-01

A deep exposure of the bright star Arcturus (Alpha Bootis: K1 III) with the Roentgensatellit (Rosat) failed to detect soft X-ray emission from the archetype 'noncoronal' red giant. The 3-sigma upper limit in the energy band 0.1-2.4 keV corresponds to an X-ray luminosity of less than 3 x 10 to the 25th erg/s, equivalent to a coronal surface flux density of less than 0.0001 solar. The nondetection safely eliminates coronal irradiation as a possible mechanism to produce the highly variable He I 10830 feature and emphasizes the sharp decline in solarlike coronal activity that accompanies the evolution of low-mass single stars away from the main sequence. While the most conspicuous object in the Rosat field of view was not visible in X-rays, at least one fainter star is among the about 60 sources recorded: the Sigma Sct variable CN Boo, an A8 giant in the UMa Stream.

Can the starpatch on Xi Bootis A be explained by using tangential flows?

NASA Technical Reports Server (NTRS)

Toner, Clifford G.; Labonte, Barry J.

1991-01-01

It is demonstrated that a modification of the starpatch model of Toner and Gray (1988), using tangential flows instead of an enhanced granulation velocity dispersion within the patch, is very successful at reproducing both the observed line asymmetry and the line broadening variations observed in the G8 dwarf Xi Boo A. Areal coverage of 10 percent + or - 3 percent of the visible disk, latitude 30 deg + or - 4 deg, mean brightness 0.85 + or - 0.05 relative to the 'quiet' photosphere, mean tangential flow velocities of 8.0 + or - 1.5 km/s, and dispersions about the mean of 8/0 + or - 2.0 km/s are inferred for the patch. A feature at a latitude of about 30 deg is inferred which covers about 10 percent of the visible disk and is 10-20 percent fainter than the rest of the photosphere. It is inferred that 70-80 percent of the patch is penumbra.

Evidence against the "booty pack": Trichomonas not associated with gonorrhea or Chlamydia.

PubMed

Wegner, Stephen; Yen, M Jim; Witting, Michael

2009-08-01

Many Emergency Physicians armed with a positive Trichomonas wet mount will also treat for Neisseria gonorrhea (GC) and Chlamydia trachomatis (CT). This study estimates the association between Trichomonas microscopy result and a DNA test result for GC or CT. Using laboratory records from patients who had simultaneous sampling for all three infections, we calculated an odds ratio for the association between the Trichomonas result and a positive test for either GC or CT. Among 795 eligible females, 105 (13%) had Trichomonas, 74 (9%) had CT, and 35 (4%) had GC. Whereas CT and GC were strongly associated with each other (odds ratio 5.9, 95% confidence interval 2.8-12.4, p < 0.0001), Trichomonas infection was unrelated to infection with either GC or CT (odds ratio 1.1, 95% confidence interval 0.6-2, p = 0.9). Trichomonas results do not predict results for GC and CT; they should not influence the decision to treat for GC and CT.

Evaluation of Thermodynamic Models for Predicting Phase Equilibria of CO2 + Impurity Binary Mixture

NASA Astrophysics Data System (ADS)

Shin, Byeong Soo; Rho, Won Gu; You, Seong-Sik; Kang, Jeong Won; Lee, Chul Soo

2018-03-01

For the design and operation of CO2 capture and storage (CCS) processes, equation of state (EoS) models are used for phase equilibrium calculations. Reliability of an EoS model plays a crucial role, and many variations of EoS models have been reported and continue to be published. The prediction of phase equilibria for CO2 mixtures containing SO2, N2, NO, H2, O2, CH4, H2S, Ar, and H2O is important for CO2 transportation because the captured gas normally contains small amounts of impurities even though it is purified in advance. For the design of pipelines in deep sea or arctic conditions, flow assurance and safety are considered priority issues, and highly reliable calculations are required. In this work, predictive Soave-Redlich-Kwong, cubic plus association, Groupe Européen de Recherches Gazières (GERG-2008), perturbed-chain statistical associating fluid theory, and non-random lattice fluids hydrogen bond EoS models were compared regarding performance in calculating phase equilibria of CO2-impurity binary mixtures and with the collected literature data. No single EoS could cover the entire range of systems considered in this study. Weaknesses and strong points of each EoS model were analyzed, and recommendations are given as guidelines for safe design and operation of CCS processes.

Control of iron nitride layers growth kinetics in the binary Fe-N system

NASA Astrophysics Data System (ADS)

Torchane, L.; Bilger, P.; Dulcy, J.; Gantois, M.

1996-07-01

This study is within the framework of a research program dedicated to defining the optimal conditions for the nitriding of iron and steels at atmospheric pressure by using various mixtures, NH3-N2-H2 and NH3-Ar. After studying the mechanisms of phase formation and mass transfer at the gas-solid interface, a mathematical model is developed in order to predict the nitrogen transfer rate in the solid, the nitride layer growth rate, and the nitrogen concentration profiles. In order to validate the model and to show its possibilities, it is compared with thermogravimetric experiments, analyses, and metallurgical observations (X-ray diffraction, optical microscopy, and electron microprobe anal-ysis). The results obtained allow us to demonstrate the sound correlation between the experimental results and the theoretical predictions. By applying the model to the iron-nitrogen binary system, when the ɛ/γ/α configuration referred to the Fe-N phase diagram is formed, we have experimentally determined the effective diffusion coefficient of nitrogen in the ɛ phase. The latter is constant for a composition of the ɛ nitride between 8 and 9.5 wt pct nitrogen. All the results obtained show that it is possible, by means of dynamic gas flow regulation, to eliminate the incubation period and to control the thickness, composition, and structure of the compound layer at the beginning of the treatment.

Validity of Binary Collision Theory in Ion-Surface Interactions at 50-500 eV

NASA Astrophysics Data System (ADS)

Gordon, Michael; Giapis, Kostas

2003-10-01

Ion-surface interactions in the 50-500 eV regime have become increasingly important in plasma processing. Concerns exist in literature about the validity of the binary collision approximation (BCA) at low impact energies because peculiarities are frequently seen in the scattered ion energy distribution. Sub-surface processes, multiple bouncing, and super-elastic phenomena have all been hypothesized. This talk will explore the usefulness of BCA theory in predicting energy transfer during ion-surface collisions in the 50-500 eV energy range. Well-defined beams of rare gas ions (Ne, Ar, Kr) were scattered off semiconductor (Si, Ge) and metal surfaces (Ag, Au, Ni, Nb) to measure energy loss upon impact. The ion beams were produced from a floating ICP reactor coupled to a small accelerator beamline for transport and mass filtering. Exit channel energies were measured using a 90 gegree electrostatic sector coupled to a quadrupole mass filter with single ion detection capability. Although the BCA presents an over-simplified picture of the collision process, our results demonstrate that it is remarkably accurate in the low energy range for a variety of projectile-target combinations. In addition, reactive ion scattering of O2+ and O+ on inert and reactive surfaces (Au vs. Ag, Pt) suggests there may be rather high energy threshold processes which determine exit channel selectivity.

75 FR 58340 - Airworthiness Directives; Koito Industries, Ltd., Seats and Seating Systems Approved Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

...-105, AFS-136, AFS-235, AFS-315, ARS-183, ARS-189, ARS-190, ARS-200, ARS-242, ARS-242-TA, ARS-254, ARS-255, ARS-263, ARS-276, ARS- 277, ARS-281, ARS-289, ARS-29, ARS-29-03, ARS-304, ARS-308, ARS-311, ARS-311-A, ARS-311-B, ARS-336, ARS[dash]339, ARS-341, ARS-347 ARS-352, ARS-354, ARS-357, ARS-360, ARS-384...

Ruling out unresolved binaries in five transitional disks. VLT/NACO deep 2.12 and 1.75 μm narrow-band imaging

NASA Astrophysics Data System (ADS)

Vicente, S.; Merín, B.; Hartung, M.; Bouy, H.; Huélamo, N.; Artigau, E.; Augereau, J.-C.; van Dishoeck, E.; Olofsson, J.; Oliveira, I.; Prusti, T.

2011-09-01

Context. The presence of unresolved binaries on sub-arsecond scales could explain the existence of optically thin inner holes or gaps in circumstellar disks, which are commonly referred to as "transitional" or "cold" disks, and it is the first scenario to check before making any other assumptions. Aims: We aim at detecting the presence of companions inside the inner hole/gap region of a sample of five well known transitional disks using spatially-resolved imaging in the near-IR with the VLT/NACO/S13 camera, which probes projected distances from the primary of typically 0.1 to 7 arcsec. The sample includes the stars DoAr 21, HD 135344B (SAO 206462), HR 4796A, T Cha, and TW Hya, spanning ages of less than 1 to 10 Myr, spectral types of A0 to K7, and hole/gap outer radii of 4 to 100 AU. Methods: In order to enhance the contrast and to avoid saturation at the core of the point-spread function (PSF), we use narrow-band filters at 1.75 and 2.12 μm. The "locally optimized combination of images" (LOCI) algorithm is applied for an optimal speckle noise removal and PSF subtraction, providing an increase of 0.5-1.5 mag in contrast over the classic method. Results: With the proviso that we could have missed companions owing to unfavorable projections, the VLT/NACO observations rule out the presence of unresolved companions down to an inner radius of about 0.1 arcsec from the primary in all five transitional disks and with a detection limit of 2 to 5 mag in contrast. In the disk outer regions the detection limits typically reach 8 to 9 mag in contrast and 4.7 mag for T Cha. Hence, the NACO images resolve part of the inner hole/gap region of all disks with the exception of TW Hya, for which the inner hole is only 4 AU. The 5σ sensitivity profiles, together with a selected evolutionary model, allow to discard stellar companions within the inner hole/gap region of T Cha, and down to the substellar regime for HD 135344B and HR 4796A. DoAr 21 is the only object from the sample of five disks for which the NACO images are sensitive enough for a detection of objects less massive than ~13 MJup that is, potential giant planets or low-mass brown dwarfs at radii larger than ~76 AU (0.63 arcsec). Conclusions: These new VLT/NACO observations further constrain the origin of the inner opacity cavities to be owing to closer or lower-mass companions or other mechanisms such as giant planet formation, efficient grain growth, and photoevaporation (for DoAr 21 and HR 4796A).

Infrared and Microwave Spectra of Ne-WATER Complex

NASA Astrophysics Data System (ADS)

Liu, Xunchen; Thomas, Javix; Xu, Yunjie; Hou, Dan; Li, Hui

2016-06-01

The binary complex of rare gas atom and water is an ideal model to study the anisotropic potential energy surface of van der Waals interaction and the large amplitude motion. Although Xe-H_2O, Kr-H_2O, Ar-H_2O, Ar-D_2O and even Ne-D_2O complexes were studied by microwave or high resolution infrared spectroscopy, the lighter Ne-H_2O complex has remained unidentified. In this talk, we will present the theoretical and experimental investigation of the Ne-H_2O complex. A four-dimension PES for H_2O-Ne which only depended on the intramolecular (Q2) normal-mode coordinate of H2O monomer was calculated in this work to determine the rovibrational energy levels and mid-infrared transitions. Aided with the calculated transitions, we were able to assigned the high resolution mid-infrared spectra of both 20Ne-H_2O and 22Ne-H_2O complexes that are generated with a pulsed supersonic molecular beam in a multipass direct absorption spectrometer equiped with an external cavity quantum cascade laser at 6 μm. Several bands of both para and ortho Ne-H2O were assigned and fitted using the Hamiltonian with strong Coriolis and angular-radical coupling terms. The predicted groud state energy levels are then confirmed by the J=1-0 and J=2-1 transitions measurement using a cavity based Fourier transform microwave spectrometer.

Obtaining phase-pure CZTS thin films by annealing vacuum evaporated CuS/SnS/ZnS stack

NASA Astrophysics Data System (ADS)

Sánchez, T. G.; Mathew, X.; Mathews, N. R.

2016-07-01

Cu2ZnSnS4 (CZTS) thin films were obtained by the sequential thermal evaporation of metal binary sulfides in the order CuS/SnS/ZnS, followed by annealing in Ar/S atmosphere. The as-grown films were annealed at different temperatures ranging between 350 and 600 °C, for 10 min. Based on the preliminary results, the temperatures 550 °C and 600 °C were selected for further optimization and a second batch of films were annealed for different time durations (10 min, 30 min and 60 min) at these temperatures in order to identify the conditions to obtain phase-pure CZTS films. The structural properties and chemical compositions at each temperature were investigated in order to optimize the phase purity and film stoichiometry. We have identified adequate and reproducible conditions to obtain the elemental ratio Cu/(Zn+Sn) and Zn/Sn close to 0.78 and 1.19 respectively, which is in the range of material composition required for promising solar cells. In addition the optimized material showed excellent optical and electrical properties to be used as a photovoltaic absorber layer. The optical band gap was found to be about 1.52 eV, and the carrier concentration, hall mobility, and resistivity were in the range of 8.372×1015 cm-3, 3.103 cm2/Vs and 340.3 Ω-cm respectively. Three traps with activation energies 4.39, 8.1, and 34 meV were detected.

1ES 1113+432: Luminous, soft X-ray outburst from a nearby cataclysmic variable (AR Ursae Majoris)

NASA Technical Reports Server (NTRS)

Remillard, R. A.; Schachter, J. F.; Silber, A. D.; Slane, P.

1994-01-01

A remarkable X-ray transient from the Einstein Slew Survey, 1 ES 1113+432, is identified with a nearby, short-period cataclysmic variable. Wenzel (1993) has confirmed that the optical counterpart is the variable star, AR UMa (cataloged as 'semiregular'), erroneously reported 5.7 min southeast of the true position. One of the Einstein slew observations recorded a flux of 43 IPC counts/s, which is an order of magnitude above the flux observed from the brightest cataclysmic variables in other X-ray surveys. The outburst spectrum is extremely 'soft,' with an implied blackbody temperature of approximately 22 eV. The optical counterpart (V = 16.5) exhibits a strong UV component, TiO bands from an M star, and broadened Balmer emission lines. Optical states as bright as V approx. 13 were found on photographs from the Harvard Plate Library, confirming outburst behavior in the optical counterpart. The historical photographic record suggests that 1ES 1113+432 remains in a low-accretion state most of the time. Both of the soft X-ray spectrum and the transitions between high and low-accretion states are suggestive of the AM Her (magnetic) subclass. Photometric observations in the I band show 0.18 mag modulations at a period of 0.966 hr. These are interpreted as ellipsiodal variations in the secondary star for a binary period of 1.932 hr, which is near the lower boundary of the 'period gap' in the histogram, of orbital periods of accreting white dwarfs. Thus 1ES 1113+432 provides the rare opportunity to study a secondary star in a cataclysmic binary that has evolved through the period gap. The optical spectral features from the secondary imply a spectral type of approximately M6 and a distance of approximately 88 pc. The peak luminosity in the soft X-ray component (unabsorbed) is then estimated to be 3 X 10(exp 33) ergs/s, assuming emission from a blackbody slab with a temperature of 22 eV. While this luminosity is higher than previous measures of the soft X-ray component, it does not exceed the amount of radiation that could be emitted from the accretion-heated surface of a white dwarf.

Torques on Sedna by a Putative Massive Body in the Oort Cloud

NASA Astrophysics Data System (ADS)

Matese, J. J.; Lissauer, J. J.

2004-11-01

Morbidelli and Levison (arXiv:astro-ph/0403358) consider various scenarios for the origin of the orbits of Sedna-like objects. The only one which they find to give satisfactory results is the passage of a low-velocity solar-mass star at about 800 AU during the early solar environment. They observe that creating ``extended scattered disk objects" (in which the largest orbits also have the largest q) requires a perturbation ``from the outside", but do not discuss the possibility that the external perturbation could come from a Jovian-mass wide-binary solar companion. We investigate the parameter space of such an object which would adiabatically detach Sedna from Neptune's dominance with qS (0) ≈ 30 AU, aS = 531 AU. Demanding that the detached osculating orbit satisfy qmin>15 AU, qmax >75 AU, the companion's mass and orbit parameters (m, a, e) that can produce n osculation cycles in a time Δ t are $(m)/(MJup)≈ n/tssΔ t (a)/(6000 AU)3(1-e^2)3/2. A wide-binary companion could also be the source of the 7^° misalignment of the ecliptic plane normal with the solar spin axis (Hogg, Quinlan and Tremaine 1991, Astron. J. 101(6), 2274), but only if n≈ 100$. The solar impulse considered by Morbidelli and Levison would produce an ecliptic plane tilt only 1/100 of that observed. J.J.L. received support from Planetary Geology and Geophysics Grant 344-30-1L.

Far-UV Spectroscopy of Two Extremely Hot, Helium-Rich White Dwarfs

NASA Technical Reports Server (NTRS)

Werner, K.; Rauch, T.; Kruk, J. W.

2017-01-01

A large proportion of hot post-asymptotic giant branch stars and white dwarfs (WDs) are hydrogen-deficient. Two distinct evolutionary sequences have been identified. One of them comprises stars of spectral type [WC] and PG1159, and it originates from a late helium-shell flash, creating helium-rich stellar atmospheres with significant admixtures of carbon (up to about 50, mass fraction). The other sequence comprises stars of spectral type O(He) and luminous subdwarf O stars which possibly are descendants of RCrB stars and extreme helium stars. Their carbon abundances are significantly lower (of the order of 1 or less) and it is thought that they originate from binary-star evolution (through merger or common-envelope evolution). Here we investigate two of the three hottest known helium-rich (DO) WDs (PG 1034+001 and PG 0038+199). They are the only ones for which spectra were recorded with the Far Ultraviolet Spectroscopic Explorer and the Hubble Space Telescope, allowing a comprehensive ultraviolet spectral analysis. We find effective temperatures of T(eff) =115000 +/- 5000 K and 125000 +/- 5000 K, respectively, and a surface gravity of log g = 7 +/-0.5. In both stars, nitrogen is strongly oversolar while C and O are significantly subsolar. For all other assessed metals (Ne, Si, P, S, Ar, Fe, and Ni) we find abundances close to solar. We conclude that these WDs are immediate descendants of O(He) stars and, hence, result from close-binary evolution.

Electron-ion recombination in low temperature hydrogen/deuterium plasma

NASA Astrophysics Data System (ADS)

Glosík, Juraj; Dohnal, Petr; Kálosi, Ábel; Augustovičová, Lucie D.; Shapko, Dmytro; Roučka, Štěpán; Plašil, Radek

2018-01-01

The stationary afterglow with cavity ring down spectrometer (SA-CRDS) was used to study the recombination of H3+, H2D+, HD2+ and D3+ ions with electrons in low temperature (77-300 K) plasmas in He/Ar/H2/D2 gas mixtures. By measuring effective recombination rate coefficients (αeff) in plasma with mixtures of ions and their dependences on temperature and partial densities of He, H2 and D2, αeff (T, [He],[H2],[D2]), we determined binary (αbinH3, αbinH2D, αbinHD2, αbinD3) and ternary (KH3, KH2D, KHD2, KD3) recombination rate coefficients for H3+, H2D+, HD2+ and D3+ ions. For all four ions we observed very efficient He assisted ternary recombination which is comparable with binary recombination already at [He] =1 × 1017 cm-3. The removal of excited particles in afterglow plasma was monitored to obtain the plasma thermalisation rate at given experimental conditions. The inferred deexcitation rates for reaction of helium metastable atoms with D2 are kD2 (300 K)=(2.1 ± 0.3) × 10-10 cm3 s-1 and kD2 (140 K)=(1.3 ± 0.3) × 10-10 cm3 s-1. Contribution to the topical issue "Plasma Sources and Plasma Processes (PSPP)", edited by Luis Lemos Alves, Thierry Belmonte and Tiberiu Minea.

23 CFR Appendix C to Part 658 - Trucks Over 80,000 Pounds on the Interstate System and Trucks Over STAA Lengths on the National...

Code of Federal Regulations, 2011 CFR

2011-04-01

... of Utah Utah US 160 US 163 New Mexico US 163 US 160 Utah LEGAL CITATIONS ARS 28-107 ARS 28-1009 ARS 28-1011.O ARS 28-108.5 ARS 28-1009.01 ARS 28-1012 ARS 28-108.13 ARS 28-1011.A ARS 28-1013 ARS 28-108.14 ARS 28-1011.C ARS 28-1014 ARS 28-403 ARS 28-1011.F ARS 28-1031 ARS 28-405 ARS 28-1011.K ARS 28...

23 CFR Appendix C to Part 658 - Trucks Over 80,000 Pounds on the Interstate System and Trucks Over STAA Lengths on the National...

Code of Federal Regulations, 2014 CFR

2014-04-01

... of Utah Utah US 160 US 163 New Mexico US 163 US 160 Utah LEGAL CITATIONS ARS 28-107 ARS 28-1009 ARS 28-1011.O ARS 28-108.5 ARS 28-1009.01 ARS 28-1012 ARS 28-108.13 ARS 28-1011.A ARS 28-1013 ARS 28-108.14 ARS 28-1011.C ARS 28-1014 ARS 28-403 ARS 28-1011.F ARS 28-1031 ARS 28-405 ARS 28-1011.K ARS 28...

23 CFR Appendix C to Part 658 - Trucks Over 80,000 Pounds on the Interstate System and Trucks Over STAA Lengths on the National...

Code of Federal Regulations, 2013 CFR

2013-04-01

... of Utah Utah US 160 US 163 New Mexico US 163 US 160 Utah LEGAL CITATIONS ARS 28-107 ARS 28-1009 ARS 28-1011.O ARS 28-108.5 ARS 28-1009.01 ARS 28-1012 ARS 28-108.13 ARS 28-1011.A ARS 28-1013 ARS 28-108.14 ARS 28-1011.C ARS 28-1014 ARS 28-403 ARS 28-1011.F ARS 28-1031 ARS 28-405 ARS 28-1011.K ARS 28...

23 CFR Appendix C to Part 658 - Trucks Over 80,000 Pounds on the Interstate System and Trucks Over STAA Lengths on the National...

Code of Federal Regulations, 2010 CFR

2010-04-01

... of Utah Utah US 160 US 163 New Mexico US 163 US 160 Utah LEGAL CITATIONS ARS 28-107 ARS 28-1009 ARS 28-1011.O ARS 28-108.5 ARS 28-1009.01 ARS 28-1012 ARS 28-108.13 ARS 28-1011.A ARS 28-1013 ARS 28-108.14 ARS 28-1011.C ARS 28-1014 ARS 28-403 ARS 28-1011.F ARS 28-1031 ARS 28-405 ARS 28-1011.K ARS 28...

23 CFR Appendix C to Part 658 - Trucks Over 80,000 Pounds on the Interstate System and Trucks Over STAA Lengths on the National...

Code of Federal Regulations, 2012 CFR

2012-04-01

... of Utah Utah US 160 US 163 New Mexico US 163 US 160 Utah LEGAL CITATIONS ARS 28-107 ARS 28-1009 ARS 28-1011.O ARS 28-108.5 ARS 28-1009.01 ARS 28-1012 ARS 28-108.13 ARS 28-1011.A ARS 28-1013 ARS 28-108.14 ARS 28-1011.C ARS 28-1014 ARS 28-403 ARS 28-1011.F ARS 28-1031 ARS 28-405 ARS 28-1011.K ARS 28...

A nonradial pulsation model for the rapidly rotating Delta Scuti star Kappa(2) Bootis

NASA Technical Reports Server (NTRS)

Kennelly, E. J.; Walker, G. A. H.; Hubeny, I.

1991-01-01

A sectorial nonradial pulsation model is used to construct theoretical line profiles which mimic the variations for Kappa(2) Boo. Synthetic spectra generated with the appropriate Teff and log g are used as input. It is found that the data can be reproduced by the combination of a high-degree l is approximately equal to 12 mode with P(osc) aproximately equal to 0.071 d, and a low-degree mode, l is approximately equal to 0-2 with P(osc) approximately equal to 0.071-0.079 d. The projected rotational velocity (v sin i - 115 +/-5 km/s) was determined by fitting synthetic line profiles to the observed spectra. The velocity amplitude of the high-degree oscillations is estimated to be about 3.5 km/s. It is found that the ratio of the horizontal and radial pulsation amplitudes is small (about 0.02) and consistent with p-mode oscillations. Comparisons are made with models invoking starspots, and it is impossible to fit the observations of Kappa(2) Boo by a starspot model without assuming unrealistic values of radius or equatorial velocity.

Spectral Irradiance Calibration in the Infrared. 11; Comparison of (alpha) Bootis and 1 Ceres with a Laboratory Standard

NASA Technical Reports Server (NTRS)

Witteborn, Fred C.; Cohen, Martin; Bregman, Jesse D.; Wooden, Diane H.; Heere, Karen; Shirley, Eric L.

1999-01-01

Infrared spectra of two celestial objects frequently used as flux standards are calibrated against an absolute laboratory flux standard at a spectral resolving power of 100 to 200. The spectrum of the KI.5 III star alpha Boo is measured from 3 to 30 microns, and that of the C-type asteroid 1 Ceres from 5 to 30 microns. While these "standard" spectra do not have the apparent precision of those based on calculated models, they do not require the assumptions involved in theoretical models of stars and asteroids. Specifically, they provide a model-independent means of calibrating celestial flux in the spectral range from 12 to 30 microns, where accurate absolute photometry is not available. The agreement found between the spectral shapes of alpha Boo and Ceres based on laboratory standards and those based on observed ratios to alpha CMa (Sirius) and alpha Lyr (Vega), flux-calibrated by theoretical modeling of these hot stars, strengthens our confidence in the applicability of the stellar models as primary irradiance standards.

Interplay Between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediate Castration Resistance

PubMed Central

Zhan, Yang; Zhang, Guanyi; Wang, Xiaojie; Qi, Yanfeng; Bai, Shanshan; Li, Dongying; Ma, Tianfang; Sartor, Oliver; Flemington, Erik K.; Zhang, Haitao; Lee, Peng; Dong, Yan

2016-01-01

Androgen receptor splice variants (AR-Vs) are implicated in resistance of prostate cancer to androgen-directed therapies. When expressed alone in cells, some AR-Vs (e.g., AR-V7) localize primarily to the nucleus, whereas others (e.g., AR-V1, AR-V4, and AR-V6) localize mainly to the cytoplasm. Significantly, the latter are often co-expressed with the nucleus-predominant AR-Vs and the full-length AR (AR-FL). An important question to be addressed is whether the cytoplasmic-localized AR-Vs play a role in castration-resistant prostate cancer (CRPC) through interaction with the nucleus-predominant AR-Vs and AR-FL. Here, it is demonstrated that AR-V1, -V4, and -V6 can dimerize with both AR-V7 and AR-FL. Consequently, AR-V7 and androgen-bound AR-FL induced nuclear localization of AR-V1, -V4, and -V6, and these variants, in turn, mitigated the ability of the anti-androgen enzalutamide to inhibit androgen-induced AR-FL nuclear localization. Interestingly, the impact of nuclear localization of AR-V4 and -V6 on AR transactivation differs from that of AR-V1. Nuclear localization leads to an increased ability of AR-V4 and -V6 to transactivate both canonical AR targets and AR-V-specific targets and to confer castration-resistant cell growth. However, while AR-V1, which lacks inherent transcriptional activity, appears to activate AR-FL in an androgen-independent manner, it significantly antagonizes AR-V7 transactivation. Together, these data demonstrate that the complex interactions among different AR-Vs and AR-FL play a significant role in castration resistant disease. Implications This study suggests important consequences for clinical castration resistance due to simultaneous expression of AR-FL and AR-Vs in patient tumors and suggests that dissecting these interactions should help develop effective strategies to disrupt AR-V signaling. PMID:27671337

Water vapour masers in long-period variable stars. I. RX Bootis and SV Pegasi

NASA Astrophysics Data System (ADS)

Winnberg, A.; Engels, D.; Brand, J.; Baldacci, L.; Walmsley, C. M.

2008-05-01

Context: Water vapour maser emission from late-type stars characterises them as asymptotic-giant-branch stars with oxygen-rich chemistry that are losing mass at a substantial rate. Further conclusions on the properties of the stars, however, are hampered by the strong variability of the emission. Aims: We wish to understand the reasons for the strong variability of H2O masers in circumstellar shells of late-type stars. In this paper we study RX Bootis and SV Pegasi as representatives of semiregular variable stars (SRVs). Methods: We monitored RX Boo and SV Peg in the 22-GHz maser line of water vapour with single-dish telescopes. The monitoring period covered two decades for RX Boo (1987-2007) and 12 years for SV Peg (1990-1995, 2000-2007). In addition, maps were obtained of RX Boo with the Very Large Array over several years. Results: We find that most of the emission in the circumstellar shell of RX Boo is located in an incomplete ring with an inner radius of 91 mas (15 AU). A velocity gradient is found in a NW-SE direction. The maser region can be modelled as a shell with a thickness of 22 AU, which is only partially filled. The gas crossing time is 16.5 years. The ring-like structure and the velocity gradient remained stable for at least 11 years, while the maser line profiles varied strongly. This suggests that the spatial asymmetry is not accidental, so that either the mass loss process or the maser excitation conditions in RX Boo are not spherically symmetric. The strong variability of the maser spectral features is mainly due to incoherent intensity fluctuations of maser emission spots, which have lifetimes of the order of 1 year. We found no correlation between the optical and the maser variability in either star. The variability properties of the SV Peg masers do not differ substantially from those of RX Boo. There were fewer spectral features present, and the range of variations was narrower. The maser was active on the >10-Jy level only 1990-1992 and 2006/2007. At other times the maser was either absent (<1 Jy) or barely detectable. Conclusions: The variability of H2O masers in the SRVs RX Boo and SV Peg is due to the emergence and disappearance of maser clouds with lifetimes of ~1 year. The emission regions do not evenly fill the shell of RX Boo leading to asymmetry in the spatial distribution, which persists at least an order of magnitude longer. Appendix A is only available in electronic form at http://www.aanda.org

Organic reactions mediated by electrochemically generated ArS+.

PubMed

Matsumoto, Kouichi; Suga, Seiji; Yoshida, Jun-ichi

2011-04-21

Low-temperature electrochemical oxidation of ArSSAr was carried out to generate a pool of "ArS(+)". Spectroscopic studies ((1)H NMR and CSI-MS) of the resulting solution revealed the accumulation of ArS(ArSSAr)(+). The resulting "ArS(+)" pool reacted with alkenes and alkynes to give diarylthio-substituted products. The "ArS(+)" pool rapidly reacted with thioacetals to give the corresponding alkoxycarbenium ion pools, which reacted with various carbon nucleophiles (indirect cation pool method). The reaction of the alkoxycarbenium ion pools with stilbene derivatives in the presence of ArSSAr gave thiochroman derivatives. In addition to such stoichiometric reactions, a catalytic amount of "ArS(+)" serves as an initiator and a chain carrier of some cationic chain reactions involving intramolecular carbon-carbon bond formation. In situ generation of "ArS(+)" by electrochemical oxidation of ArSSAr with a catalytic amount of electricity in the presence of a substrate is also effective for such cationic chain reactions.

Addition of ArSSAr to dienes via intramolecular C-C bond formation initiated by a catalytic amount of ArS+.

PubMed

Matsumoto, Kouichi; Fujie, Shunsuke; Suga, Seiji; Nokami, Toshiki; Yoshida, Jun-ichi

2009-09-28

A catalytic amount of electrochemically generated "ArS+" ("ArS+" = ArS(ArSSAr)+) initiates a cation chain reaction of dienes that involves the addition of ArSSAr associated with stereoselective intramolecular carbon-carbon bond formation, and the direct (in-cell) electrolysis of a mixture of a diene and ArSSAr with a catalytic amount of electricity also effectively initiates the reaction.

Ar-Ar_Redux: rigorous error propagation of 40Ar/39Ar data, including covariances

NASA Astrophysics Data System (ADS)

Vermeesch, P.

2015-12-01

Rigorous data reduction and error propagation algorithms are needed to realise Earthtime's objective to improve the interlaboratory accuracy of 40Ar/39Ar dating to better than 1% and thereby facilitate the comparison and combination of the K-Ar and U-Pb chronometers. Ar-Ar_Redux is a new data reduction protocol and software program for 40Ar/39Ar geochronology which takes into account two previously underappreciated aspects of the method: 1. 40Ar/39Ar measurements are compositional dataIn its simplest form, the 40Ar/39Ar age equation can be written as: t = log(1+J [40Ar/39Ar-298.5636Ar/39Ar])/λ = log(1 + JR)/λ Where λ is the 40K decay constant and J is the irradiation parameter. The age t does not depend on the absolute abundances of the three argon isotopes but only on their relative ratios. Thus, the 36Ar, 39Ar and 40Ar abundances can be normalised to unity and plotted on a ternary diagram or 'simplex'. Argon isotopic data are therefore subject to the peculiar mathematics of 'compositional data', sensu Aitchison (1986, The Statistical Analysis of Compositional Data, Chapman & Hall). 2. Correlated errors are pervasive throughout the 40Ar/39Ar methodCurrent data reduction protocols for 40Ar/39Ar geochronology propagate the age uncertainty as follows: σ2(t) = [J2 σ2(R) + R2 σ2(J)] / [λ2 (1 + R J)], which implies zero covariance between R and J. In reality, however, significant error correlations are found in every step of the 40Ar/39Ar data acquisition and processing, in both single and multi collector instruments, during blank, interference and decay corrections, age calculation etc. Ar-Ar_Redux revisits every aspect of the 40Ar/39Ar method by casting the raw mass spectrometer data into a contingency table of logratios, which automatically keeps track of all covariances in a compositional context. Application of the method to real data reveals strong correlations (r2 of up to 0.9) between age measurements within a single irradiation batch. Propertly taking into account these correlations significantly improves the precision and accuracy of 40Ar/39Ar data, at no financial cost. A prototype version of Ar-Ar_Redux was written in R and is available from http://redux.london-geochron.com. A standalone GUI is under development.

The spectroscopic orbits and the geometrical configuration of the symbiotic binary AR Pavonis

NASA Astrophysics Data System (ADS)

Quiroga, C.; Mikołajewska, J.; Brandi, E.; Ferrer, O.; García, L.

2002-05-01

We analyze optical and near infrared spectra of intermediate and high resolution of the eclipsing symbiotic system AR Pavonis. We have obtained the radial velocity curves for the red and the hot component from the M-giant absorption lines and from the wings of Hα , Hβ and He II lambda 4686 emission profiles, respectively. From the orbital elements we have derived the masses, Mg=2.5 Msun and Mh=1.0 Msun, for the red giant and the hot component, respectively. We also present and discuss radial velocity patterns in the blue cF absorption spectrum as well as various emission lines. In particular, we confirm that the blue absorption lines are associated with the hot component. The radial velocity curve of the blue absorption system, however, does not track the hot companion's orbital motion in a straightforward way, and its departures from an expected circular orbit are particularly strong when the hot component is active. We suggest that the cF-type absorption system is formed in material streaming from the giant presumably in a region where the stream encounters an accretion disk or an extended envelope around the hot component. The broad emission wings originate from the inner accretion disk or the envelope around the hot star. We also suggest that the central absorption in H profiles is formed in a neutral portion of the cool giant's wind which is strongly concentrated towards the orbital plane. The nebula in AR Pav seems to be bounded by significant amount of neutral material in the orbital plane. The forbidden emission lines are probably formed in low density ionized regions extended in polar directions and/or the wind-wind interaction zone. Based on observations taken at Complejo Astronómico El Leoncito (CASLEO), operated under an agreement between the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, the Secretaría de Ciencia y Tecnología de la Nación and the National Universities of La Plata, Córdoba and San Juan.

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

El-Atwani, O.; Norris, S. A.; Ludwig, K.

In this study, several proposed mechanisms and theoretical models exist concerning nanostructure evolution on III-V semiconductors (particularly GaSb) via ion beam irradiation. However, making quantitative contact between experiment on the one hand and model-parameter dependent predictions from different theories on the other is usually difficult. In this study, we take a different approach and provide an experimental investigation with a range of targets (GaSb, GaAs, GaP) and ion species (Ne, Ar, Kr, Xe) to determine new parametric trends regarding nanostructure evolution. Concurrently, atomistic simulations using binary collision approximation over the same ion/target combinations were performed to determine parametric trends onmore » several quantities related to existing model. A comparison of experimental and numerical trends reveals that the two are broadly consistent under the assumption that instabilities are driven by chemical instability based on phase separation. Furthermore, the atomistic simulations and a survey of material thermodynamic properties suggest that a plausible microscopic mechanism for this process is an ion-enhanced mobility associated with energy deposition by collision cascades.« less

Eta Carinae: Viewed from Multiple Vantage Points

NASA Technical Reports Server (NTRS)

Gull, Theodore

2007-01-01

The central source of Eta Carinae and its ejecta is a massive binary system buried within a massive interacting wind structure which envelops the two stars. However the hot, less massive companion blows a small cavity in the very massive primary wind, plus ionizes a portion of the massive wind just beyond the wind-wind boundary. We gain insight on this complex structure by examining the spatially-resolved Space Telescope Imaging Spectrograph (STIS) spectra of the central source (0.1") with the wind structure which extends out to nearly an arcsecond (2300AU) and the wind-blown boundaries, plus the ejecta of the Little Homunculus. Moreover, the spatially resolved Very Large Telescope/UltraViolet Echelle Spectrograph (VLT/UVES) stellar spectrum (one arcsecond) and spatially sampled spectra across the foreground lobe of the Homunculus provide us vantage points from different angles relative to line of sight. Examples of wind line profiles of Fe II, and the.highly excited [Fe III], [Ne III], [Ar III] and [S III)], plus other lines will be presented.

Polarimetric and diffractive evaluation of 3.74 micron pixel-size LCoS in the telecommunications C-band

NASA Astrophysics Data System (ADS)

Wang, Mi; Martínez, Francisco J.; Márquez, Andrés.; Ye, Yabin; Zong, Liangjia; Pascual, Inmaculada; Beléndez, Augusto

2017-08-01

Liquid-crystal on Silicon (LCoS) microdisplays are one of the competing technologies to implement wavelength selective switches (WSS) for optical telecommunications. Last generation LCoS, with more than 4 megapixels, have decreased pixel size to values smaller than 4 microns, what increases interpixel cross-talk effects such as fringing-field. We proceed with an experimental evaluation of a 3.74 micron pixel size parallel-aligned LCoS (PA-LCoS) device. At 1550 nm, for the first time we use time-average Stokes polarimetry to measure the retardance and its flicker magnitude as a function of voltage. We also verify the effect of the antireflection coating when we try to characterize the PA-LCoS out of the designed interval for the AR coating. Some preliminary results for the performance for binary gratings are also given, where the decrease of modulation range with the increase in spatial frequency is shown, together with some residual polarization effects.

Improving soft FEC performance for higher-order modulations via optimized bit channel mappings.

PubMed

Häger, Christian; Amat, Alexandre Graell I; Brännström, Fredrik; Alvarado, Alex; Agrell, Erik

2014-06-16

Soft forward error correction with higher-order modulations is often implemented in practice via the pragmatic bit-interleaved coded modulation paradigm, where a single binary code is mapped to a nonbinary modulation. In this paper, we study the optimization of the mapping of the coded bits to the modulation bits for a polarization-multiplexed fiber-optical system without optical inline dispersion compensation. Our focus is on protograph-based low-density parity-check (LDPC) codes which allow for an efficient hardware implementation, suitable for high-speed optical communications. The optimization is applied to the AR4JA protograph family, and further extended to protograph-based spatially coupled LDPC codes assuming a windowed decoder. Full field simulations via the split-step Fourier method are used to verify the analysis. The results show performance gains of up to 0.25 dB, which translate into a possible extension of the transmission reach by roughly up to 8%, without significantly increasing the system complexity.

Projectile-charge dependence of the differential cross section for the ionization of argon atoms at 1 keV

NASA Astrophysics Data System (ADS)

Purohit, G.; Kato, D.

2017-10-01

The single ionization triple differential cross sections (TDCS) of the Ar (3 p ) atoms are reported for the positron and electron impact at 1 keV. The calculated cross sections have been obtained using distorted wave Born approximation (DWBA) approach for the average ejected electron energies 13 and 26 eV at different momentum transfer conditions. The present attempt is helpful to probe the information on the TDCS trends for the particle-matter and antiparticle-matter interactions and to analyze the recent measurements [Phy. Rev. A 95, 062703 (2017), 10.1103/PhysRevA.95.062703]. The binary electron emission is enhanced while the recoil emission is decreased for the positron impact relative to the electron impact in the DWBA calculation results. Systematic shift of peaks, shifting away from the momentum transfer direction for positron impact and shifting towards each other for electron impact, is observed with increasing momentum transfer.

The mechanical properties of high speed GTAW weld and factors of nonlinear multiple regression model under external transverse magnetic field

NASA Astrophysics Data System (ADS)

Lu, Lin; Chang, Yunlong; Li, Yingmin; He, Youyou

2013-05-01

A transverse magnetic field was introduced to the arc plasma in the process of welding stainless steel tubes by high-speed Tungsten Inert Gas Arc Welding (TIG for short) without filler wire. The influence of external magnetic field on welding quality was investigated. 9 sets of parameters were designed by the means of orthogonal experiment. The welding joint tensile strength and form factor of weld were regarded as the main standards of welding quality. A binary quadratic nonlinear regression equation was established with the conditions of magnetic induction and flow rate of Ar gas. The residual standard deviation was calculated to adjust the accuracy of regression model. The results showed that, the regression model was correct and effective in calculating the tensile strength and aspect ratio of weld. Two 3D regression models were designed respectively, and then the impact law of magnetic induction on welding quality was researched.

Extension of the quasistatic far-wing line shape theory to multicomponent anisotropic potentials

NASA Technical Reports Server (NTRS)

Ma, Q.; Tipping, R. H.

1994-01-01

The formalism developed previously for the calculation of the far-wing line shape function and the corresponding absorption coefficient using a single-component anisotropic interaction term and the binary collision and quasistatic approximations is generalized to multicomponent anisotropic potential functions. Explicit expressions are presented for several common cases, including the long-range dipole-dipole plus dipole-quadrupole interaction and a linear molecule interacting with a perturber atom. After determining the multicomponent functional representation for the interaction between the CO2 and Ar from previously published data, we calculate the theoretical line shape function and the corresponding absorption due to the nu(sub 3) band of CO2 in the frequency range 2400-2580 cm(exp -1) and compare our results with previous calculations carried out using a single-component anisotropic interaction, and with the results obtained assuming Lorentzian line shapes. The principal uncertainties in the present results, possible refinements of the theoretical formalism, and the applicability to other systems are discussed briefly.

Acid-base treated vermiculite as high performance adsorbent: Insights into the mechanism of cationic dyes adsorption, regeneration, recyclability and stability studies.

PubMed

Stawiński, Wojciech; Węgrzyn, Agnieszka; Dańko, Tomasz; Freitas, Olga; Figueiredo, Sónia; Chmielarz, Lucjan

2017-04-01

Additional treatment with NaOH of acid activated vermiculite results in even higher increase in the adsorption capacity in comparison to samples modified only in acidic solution (first step of activation) with respect to raw material. Optimization of treatment conditions and adsorption capacity for two cationic dyes (methylene blue (MB) and astrazon red (AR)), also as binary mixture, was evaluated. The capacity, based on column studies, increased from 48 ± 2 to 203 ± 4 mg g -1 in the case of methylene blue and from 51 ± 1 to 127 ± 2 mg g -1 in the case of astrazon red on starting and acid-base treated material, respectively. It was shown that adsorption mechanism changes for both cationic dyes after NaOH treatment and it results in decrease of adsorption rate. In binary mixtures methylene blue is bound stronger by adsorbent and astrazon red may be removed in initial stage of adsorption. Extensive studies on desorption/regeneration process proved high efficiency in recyclable use of all materials. Although cation exchange capacity decreases due to acid treatment, after base treatment exchange properties are used more efficiently. On the other hand, increased specific surface area has less significant contribution into the adsorption potential of studied materials. Obtained adsorbents worked efficiently in 7 adsorption-regeneration cycles and loss of adsorption capacity was observed only in two first cycles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Far-UV spectroscopy of two extremely hot, helium-rich white dwarfs

NASA Astrophysics Data System (ADS)

Werner, K.; Rauch, T.; Kruk, J. W.

2017-05-01

A large proportion of hot post-asymptotic giant branch stars and white dwarfs (WDs) are hydrogen-deficient. Two distinct evolutionary sequences have been identified. One of them comprises stars of spectral type [WC] and PG1159, and it originates from a late helium-shell flash, creating helium-rich stellar atmospheres with significant admixtures of carbon (up to about 50%, mass fraction). The other sequence comprises stars of spectral type O(He) and luminous subdwarf O stars which possibly are descendants of RCrB stars and extreme helium stars. Their carbon abundances are significantly lower (of the order of 1% or less) and it is thought that they originate from binary-star evolution (through merger or common-envelope evolution). Here we investigate two of the three hottest known helium-rich (DO) WDs (PG 1034+001 and PG 0038+199). They are the only ones for which spectra were recorded with the Far Ultraviolet Spectroscopic Explorer and the Hubble Space Telescope, allowing a comprehensive ultraviolet spectral analysis. We find effective temperatures of Teff = 115 000 ± 5000 K and 125 000 ± 5000 K, respectively, and a surface gravity of log g= 7 ± 0.5. In both stars, nitrogen is strongly oversolar while C and O are significantly subsolar. For all other assessed metals (Ne, Si, P, S, Ar, Fe, and Ni) we find abundances close to solar. We conclude that these WDs are immediate descendants of O(He) stars and, hence, result from close-binary evolution. Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer.

Ar-39-Ar-40 Ages of Two Nakhlites, MIL03346 and Y000593: A Detailed Analysis

NASA Technical Reports Server (NTRS)

Park, Jisun; Garrison, Daniel; Bogard, Donald

2007-01-01

Radiometric dating of martian nakhlites by several techniques have given similar ages of approx.1.2-1.4 Ga [e.g. 1, 2]. Unlike the case with shergottites, where the presence of martian atmosphere and inherited radiogenic Ar-40 produce apparent Ar-39-Ar-40 ages older than other radiometric ages, Ar-Ar ages of nakhlites are similar to ages derived by other techniques. However, even in some nakhlites the presence of trapped martian Ar produces some uncertainty in the Ar-Ar age. We present here an analysis of such Ar-Ar ages from the MIL03346 and Y000593 nakhlites.

Book review: Advances in 40Ar/39Ar dating: From archaeology to planetary sciences

USGS Publications Warehouse

Cosca, Michael A.

2015-01-01

The recently published book Advances in 40Ar/39Ar Dating: From Archaeology to Planetary Sciences is a collection of 24 chapters authored by international scientists on topics ranging from decay constants to 40Ar/39Ar dating of extraterrestrial objects. As stated by the editors in their introduction, these chapters were assembled with the goal of providing technique-specific examples highlighting recent advances in the field of 40Ar/39Ar dating. As this is the first book truly dedicated to 40Ar/39Ar dating since the second edition printing of the argon geochronologist’s handbook Geochronology and Thermochronology by the 40Ar/39Ar Method (McDougall and Harrison 1999), a new collection of chapters highlighting recent advances in 40Ar/39Ar geochronology offers much to the interested reader.

Acetylation of androgen receptor by ARD1 promotes dissociation from HSP90 complex and prostate tumorigenesis

PubMed Central

Zhang, Guanyi; Qian, Chiping; Zhang, Haitao; Zabaleta, Jovanny; Liu, Wanguo

2016-01-01

Prostate cancer is an androgen receptor (AR)-driven disease and post-translational modification of AR is critical for AR activation. We previously reported that Arrest-defective protein 1 (ARD1) is an oncoprotein in prostate cancer. It acetylates and activates AR to promote prostate tumorigenesis. However, the ARD1-targeted residue within AR and the mechanisms of the acetylation event in prostate tumorigenesis remained unknown. In this study, we show that ARD1 acetylates AR at lysine 618 (K618) in vitro and in vivo. An AR construct with the charged lysine substitution by arginine (AR-618R) reduces RNA Pol II binding, AR transcriptional activity, prostate cancer cell growth, and xenograft tumor formation due to attenuation of AR nuclear translocation, whereas, construct mimicking neutral polar substitution acetylation at K618 by glutamine (AR-618Q) enhanced these effects beyond that of the wild-type AR. Mechanistically, ARD1 forms a ternary complex with AR and HSP90 in vitro and in vivo. Expression of ARD1 increases levels of AR acetylation and AR-HSP90 dissociation in a dose dependent manner. Moreover, the AR acetylation defective K618R mutant is unable to dissociate from HSP90 while the HSP90-dissociated AR is acetylated following ligand exposure. This work identifies a new mechanism for ligand-induced AR-HSP90 dissociation and AR activation. Targeting ARD1-mediated AR acetylation may be a potent intervention for AR-dependent prostate cancer therapy. PMID:27659526

Analytic Validation of RNA In Situ Hybridization (RISH) for AR and AR-V7 Expression in Human Prostate Cancer

PubMed Central

Guedes, Liana B.; Morais, Carlos L.; Almutairi, Fawaz; Haffner, Michael C.; Zheng, Qizhi; Isaacs, John T.; Antonarakis, Emmanuel S.; Lu, Changxue; Tsai, Harrison; Luo, Jun; De Marzo, Angelo M.; Lotan, Tamara L.

2016-01-01

Purpose RNA expression of androgen receptor splice variants may be a biomarker of resistance to novel androgen deprivation therapies in castrate resistant prostate cancer (CRPC). We analytically validated an RNA in situ hybridization (RISH) assay for total AR and AR-V7 for use in formalin fixed paraffin embedded (FFPE) prostate tumors. Experimental Design We used prostate cell lines and xenografts to validate chromogenic RISH to detect RNA containing AR exon 1 (AR-E1, surrogate for total AR RNA species) and cryptic exon 3 (AR-CE3, surrogate for AR-V7 expression). RISH signals were quantified in FFPE primary tumors and CRPC specimens, comparing to known AR and AR-V7 status by immunohistochemistry and RT-PCR. Results The quantified RISH results correlated significantly with total AR and AR-V7 levels by RT-PCR in cell lines, xenografts and autopsy metastases. Both AR-E1 and AR-CE3 RISH signals were localized in nuclear punctae in addition to the expected cytoplasmic speckles. Compared to admixed benign glands, AR-E1 expression was significantly higher in primary tumor cells with a median fold increase of 3.0 and 1.4 in two independent cohorts (p<0.0001 and p=0.04, respectively). While AR-CE3 expression was detectable in primary prostatic tumors, levels were substantially higher in a subset of CRPC metastases and cell lines, and were correlated with AR-E1 expression. Conclusions RISH for AR-E1 and AR-CE3 is an analytically valid method to examine total AR and AR-V7 RNA levels in FFPE tissues. Future clinical validation studies are required to determine whether AR RISH is a prognostic or predictive biomarker in specific clinical contexts. PMID:27166397

Minoxidil may suppress androgen receptor-related functions.

PubMed

Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

2014-04-30

Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a K(d) value of 2.6 µM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

Minoxidil may suppress androgen receptor-related functions

PubMed Central

Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

2014-01-01

Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 μM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases. PMID:24742982

76 FR 27077 - Agency Information Collection Activities: Form AR-11 and Form AR-11SR, Extension of an Existing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... Collection Activities: Form AR-11 and Form AR- 11SR, Extension of an Existing Information Collection; Comment Request ACTION: 60-Day Notice of Information Collection under Review: Form AR- 11 and Form AR-11SR, Alien... evaluating whether to revise the Form AR-11 and Form AR-11SR (Forms AR-11). Should USCIS decide to revise...

Arsenic resistance strategy in Pantoea sp. IMH: Organization, function and evolution of ars genes.

PubMed

Wang, Liying; Zhuang, Xuliang; Zhuang, Guoqiang; Jing, Chuanyong

2016-12-14

Pantoea sp. IMH is the only bacterium found in genus Pantoea with a high As resistance capacity, but its molecular mechanism is unknown. Herein, the organization, function, and evolution of ars genes in IMH are studied starting with analysis of the whole genome. Two ars systems - ars1 (arsR1B1C1H1) and ars2 (arsR2B2C2H2) - with low sequence homology and two arsC-like genes, were found in the IMH genome. Both ars1 and ars2 are involved in the As resistance, where ars1 is the major contributor at 15 °C and ars2 at 30 °C. The difference in the behavior of these two ars systems is attributed to the disparate activities of their arsR promoters at different temperatures. Sequence analysis based on concatenated ArsRBC indicates that ars1 and ars2 clusters may be acquired from Franconibacter helveticus LMG23732 and Serratia marcescens (plasmid R478), respectively, by horizontal gene transfer (HGT). Nevertheless, two arsC-like genes, probably arising from the duplication of arsC, do not contribute to the As resistance. Our results indicate that Pantoea sp. IMH acquired two different As resistance genetic systems by HGT, allowing the colonization of changing ecosystems, and highlighting the flexible adaptation of microorganisms to resist As.

Arsenic resistance strategy in Pantoea sp. IMH: Organization, function and evolution of ars genes

PubMed Central

Wang, Liying; Zhuang, Xuliang; Zhuang, Guoqiang; Jing, Chuanyong

2016-01-01

Pantoea sp. IMH is the only bacterium found in genus Pantoea with a high As resistance capacity, but its molecular mechanism is unknown. Herein, the organization, function, and evolution of ars genes in IMH are studied starting with analysis of the whole genome. Two ars systems - ars1 (arsR1B1C1H1) and ars2 (arsR2B2C2H2) - with low sequence homology and two arsC-like genes, were found in the IMH genome. Both ars1 and ars2 are involved in the As resistance, where ars1 is the major contributor at 15 °C and ars2 at 30 °C. The difference in the behavior of these two ars systems is attributed to the disparate activities of their arsR promoters at different temperatures. Sequence analysis based on concatenated ArsRBC indicates that ars1 and ars2 clusters may be acquired from Franconibacter helveticus LMG23732 and Serratia marcescens (plasmid R478), respectively, by horizontal gene transfer (HGT). Nevertheless, two arsC-like genes, probably arising from the duplication of arsC, do not contribute to the As resistance. Our results indicate that Pantoea sp. IMH acquired two different As resistance genetic systems by HGT, allowing the colonization of changing ecosystems, and highlighting the flexible adaptation of microorganisms to resist As. PMID:27966630

Androgen receptor (AR) cistrome in prostate differentiation and cancer progression.

PubMed

Wang, Fengtian; Koul, Hari K

2017-01-01

Despite the progress in development of better AR-targeted therapies for prostate cancer (PCa), there is no curative therapy for castration-resistant prostate cancer (CRPC). Therapeutic resistance in PCa can be characterized in two broad categories of AR therapy resistance: the first and most prevalent one involves restoration of AR activity despite AR targeted therapy, and the second one involves tumor progression despite blockade of AR activity. As such AR remains the most attractive drug target for CRPC. Despite its oncogenic role, AR signaling also contributes to the maturation and differentiation of prostate luminal cells during development. Recent evidence suggests that AR cistrome is altered in advanced PCa. Alteration in AR may result from AR amplification, alternative splicing, mutations, post-translational modification of AR, and altered expression of AR co-factors. We reasoned that such alterations would result in the transcription of disparate AR target genes and as such may contribute to the emergence of castration-resistance. In the present study, we evaluated the expression of genes associated with canonical or non-canonical AR cistrome in relationship with PCa progression and prostate development by analyzing publicly available datasets. We discovered a transcription switch from canonical AR cistrome target genes to the non-canonical AR cistrome target genes during PCa progression. Using Gene Set Enrichment Analysis (GSEA), we discovered that canonical AR cistrome target genes are enriched in indolent PCa patients and the loss of canonical AR cistrome is associated with tumor metastasis and poor clinical outcome. Analysis of the datasets involving prostate development, revealed that canonical AR cistrome target genes are significantly enriched in prostate luminal cells and can distinguish luminal cells from basal cells, suggesting a pivotal role for canonical AR cistrome driven genes in prostate development. These data suggest that the expression of canonical AR cistrome related genes play an important role in maintaining the prostate luminal cell identity and might restrict the lineage plasticity observed in lethal PCa. Understanding the molecular mechanisms that dictate AR cistrome may lead to development of new therapeutic strategies aimed at restoring canonical AR cistrome, rewiring the oncogenic AR signaling and overcome resistance to AR targeted therapies.

Calibration of Nu-Instruments Noblesse multicollector mass spectrometers for argon isotopic measurements using a newly developed reference gas

USGS Publications Warehouse

Coble, M.A.; Grove, M.; Calvert, A.T.

2011-01-01

The greatest challenge limiting 40Ar/39Ar multicollection measurements is the availability of appropriate standard gasses to intercalibrate detectors. In particular, use of zoom lens ion-optics to steer and focus ion beams into a fixed detector array (i.e., Nu Instruments Noblesse) makes intercalibration of multiple detectors challenging because different ion-optic tuning conditions are required for optimal peak shape and sensitivity at different mass stations. We have found that detector efficiency and mass discrimination are affected by changes in ion-optic tuning parameters. Reliance upon an atmospheric Ar standard to calibrate the Noblesse is problematic because there is no straightforward way to relate atmospheric 40Ar and 36Ar to measurements of 40Ar and 39Ar if they are measured on separate detectors. After exploring alternative calibration approaches, we have concluded that calibration of the Noblesse is best performed using exactly the same source, detector, and ion-optic tuning settings as those used in routine 40Ar/39Ar analysis. To accomplish this, we have developed synthetic reference gasses containing 40Ar, 39Ar and 38Ar produced by mixing gasses derived from neutron-irradiated sanidine with an enriched 38Ar spike. We present a new method for calibrating the Noblesse based on use of both atmospheric Ar and the synthetic reference gasses. By combining atmospheric Ar and synthetic reference gas in different ways, we can directly measure 40Ar/39Ar, 38Ar/39Ar, and 36Ar/39Ar correction factors over ratios that vary from 0.5 to 460. These correction factors are reproducible to better than ??0.5??? (2?? standard error) over intervals spanning ~24h but can vary systematically by ~4% over 2weeks of continuous use when electron multiplier settings are held constant. Monitoring this variation requires daily calibration of the instrument. Application of the calibration method to 40Ar/39Ar multicollection measurements of widely used sanidine reference materials ACs-2, FCs-2, and TCs-2 demonstrate that calculated 40Ar*/39ArK can be accurately corrected to yield model 40Ar/39Ar ages consistent with those reported by Earthtime 40Ar/39Ar laboratories. Replicate analyses of 8-12 single-crystal sanidine ages are reproduced to within 1-2??? (2?? standard error) under optimal analytical conditions. This calibration technique is applicable over a wide range of isotopic ratios and signal sizes. Finally, the reference gas has the added advantage of facilitating straightforward characterization of electron multiplier dead time over a wide dynamic range. ?? 2011 Elsevier B.V.

Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

PubMed

Kohli, Manish; Ho, Yeung; Hillman, David W; Van Etten, Jamie L; Henzler, Christine; Yang, Rendong; Sperger, Jamie M; Li, Yingming; Tseng, Elizabeth; Hon, Ting; Clark, Tyson; Tan, Winston; Carlson, Rachel E; Wang, Liguo; Sicotte, Hugues; Thai, Ho; Jimenez, Rafael; Huang, Haojie; Vedell, Peter T; Eckloff, Bruce W; Quevedo, Jorge F; Pitot, Henry C; Costello, Brian A; Jen, Jin; Wieben, Eric D; Silverstein, Kevin A T; Lang, Joshua M; Wang, Liewei; Dehm, Scott M

2017-08-15

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies. Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31-12.2; P = 0.02). Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Androgen Receptor and its Splice Variant, AR-V7, Differentially Regulate FOXA1 Sensitive Genes in LNCaP Prostate Cancer Cells

PubMed Central

Krause, William C.; Shafi, Ayesha A.; Nakka, Manjula; Weigel, Nancy L.

2014-01-01

Prostate cancer (PCa) is an androgen-dependent disease, and tumors that are resistant to androgen ablation therapy often remain androgen receptor (AR) dependent. Among the contributors to castration-resistant PCa are AR splice variants that lack the ligand-binding domain (LBD). Instead, they have small amounts of unique sequence derived from cryptic exons or from out of frame translation. The AR-V7 (or AR3) variant is constitutively active and is expressed under conditions consistent with CRPC. AR-V7 is reported to regulate a transcriptional program that is similar but not identical to that of AR. However, it is unknown whether these differences are due to the unique sequence in AR-V7, or simply to loss of the LBD. To examine transcriptional regulation by AR-V7, we have used lentiviruses encoding AR-V7 (amino acids 1-627 of AR with the 16 amino acids unique to the variant) to prepare a derivative of the androgen-dependent LNCaP cells with inducible expression of AR-V7. An additional cell line was generated with regulated expression of AR-NTD (amino acids 1-660 of AR); this mutant lacks the LBD but does not have the AR-V7 specific sequence. We find that AR and AR-V7 have distinct activities on target genes that are co-regulated by FOXA1. Transcripts regulated by AR-V7 were similarly regulated by AR-NTD, indicating that loss of the LBD is sufficient for the observed differences. Differential regulation of target genes correlates with preferential recruitment of AR or AR-V7 to specific cis-regulatory DNA sequences providing an explanation for some of the observed differences in target gene regulation. PMID:25008967

Variation in the terrestrial isotopic composition and atomic weight of argon

USGS Publications Warehouse

Böhlke, John Karl

2014-01-01

The isotopic composition and atomic weight of argon (Ar) are variable in terrestrial materials. Those variations are a source of uncertainty in the assignment of standard properties for Ar, but they provide useful information in many areas of science. Variations in the stable isotopic composition and atomic weight of Ar are caused by several different processes, including (1) isotope production from other elements by radioactive decay (radiogenic isotopes) or other nuclear transformations (e.g., nucleogenic isotopes), and (2) isotopic fractionation by physical-chemical processes such as diffusion or phase equilibria. Physical-chemical processes cause correlated mass-dependent variations in the Ar isotope-amount ratios (40Ar/36Ar, 38Ar/36Ar), whereas nuclear transformation processes cause non-mass-dependent variations. While atmospheric Ar can serve as an abundant and homogeneous isotopic reference, deviations from the atmospheric isotopic ratios in other Ar occurrences limit the precision with which a standard atomic weight can be given for Ar. Published data indicate variation of Ar atomic weights in normal terrestrial materials between about 39.7931 and 39.9624. The upper bound of this interval is given by the atomic mass of 40Ar, as some samples contain almost pure radiogenic 40Ar. The lower bound is derived from analyses of pitchblende (uranium mineral) containing large amounts of nucleogenic 36Ar and 38Ar. Within this interval, measurements of different isotope ratios (40Ar/36Ar or 38Ar/36Ar) at various levels of precision are widely used for studies in geochronology, water–rock interaction, atmospheric evolution, and other fields.

The Chromosomal Arsenic Resistance Genes of Thiobacillus ferrooxidans Have an Unusual Arrangement and Confer Increased Arsenic and Antimony Resistance to Escherichia coli

PubMed Central

Butcher, Bronwyn G.; Deane, Shelly M.; Rawlings, Douglas E.

2000-01-01

The chromosomal arsenic resistance genes of the acidophilic, chemolithoautotrophic, biomining bacterium Thiobacillus ferrooxidans were cloned and sequenced. Homologues of four arsenic resistance genes, arsB, arsC, arsH, and a putative arsR gene, were identified. The T. ferrooxidans arsB (arsenite export) and arsC (arsenate reductase) gene products were functional when they were cloned in an Escherichia coli ars deletion mutant and conferred increased resistance to arsenite, arsenate, and antimony. Therefore, despite the fact that the ars genes originated from an obligately acidophilic bacterium, they were functional in E. coli. Although T. ferrooxidans is gram negative, its ArsC was more closely related to the ArsC molecules of gram-positive bacteria. Furthermore, a functional trxA (thioredoxin) gene was required for ArsC-mediated arsenate resistance in E. coli; this finding confirmed the gram-positive ArsC-like status of this resistance and indicated that the division of ArsC molecules based on Gram staining results is artificial. Although arsH was expressed in an E. coli-derived in vitro transcription-translation system, ArsH was not required for and did not enhance arsenic resistance in E. coli. The T. ferrooxidans ars genes were arranged in an unusual manner, and the putative arsR and arsC genes and the arsBH genes were translated in opposite directions. This divergent orientation was conserved in the four T. ferrooxidans strains investigated. PMID:10788346

The potential of AR-V7 as a therapeutic target.

PubMed

Uo, Takuma; Plymate, Stephen R; Sprenger, Cynthia C

2018-03-01

The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome. Pharmacological agents that interfere with these processes are being developed to counteract pan AR and AR-V7-specific signaling. Also, we address the current status of the preclinical and clinical studies targeting AR-V7 signaling. Expert opinion: AR-V7 is considered a true therapeutic target, however, it remains to be determined if AR-V7 is a principal driver or merely a bystander requiring heterodimerization with co-expressed full-length AR or other variants to drive CRPC progression. While untangling AR-V7 biology, multiple strategies are being developed to counteract drug resistance, including selective blockade of AR-V7 signaling as well as inhibition of pan-AR signaling. Ideally anti-AR therapies will be combined with agents preventing activation and enrichment of AR negative tumor cells that are otherwise depressed by AR activity axis.

TALEN-engineered AR gene rearrangements reveal endocrine uncoupling of androgen receptor in prostate cancer

PubMed Central

Nyquist, Michael D.; Li, Yingming; Hwang, Tae Hyun; Manlove, Luke S.; Vessella, Robert L.; Silverstein, Kevin A. T.; Voytas, Daniel F.; Dehm, Scott M.

2013-01-01

Androgen receptor (AR) target genes direct development and survival of the prostate epithelial lineage, including prostate cancer (PCa). Thus, endocrine therapies that inhibit the AR ligand-binding domain (LBD) are effective in treating PCa. AR transcriptional reactivation is central to resistance, as evidenced by the efficacy of AR retargeting in castration-resistant PCa (CRPC) with next-generation endocrine therapies abiraterone and enzalutamide. However, resistance to abiraterone and enzalutamide limits this efficacy in most men, and PCa remains the second-leading cause of male cancer deaths. Here we show that AR gene rearrangements in CRPC tissues underlie a completely androgen-independent, yet AR-dependent, resistance mechanism. We discovered intragenic AR gene rearrangements in CRPC tissues, which we modeled using transcription activator-like effector nuclease (TALEN)-mediated genome engineering. This modeling revealed that these AR gene rearrangements blocked full-length AR synthesis, but promoted expression of truncated AR variant proteins lacking the AR ligand-binding domain. Furthermore, these AR variant proteins maintained the constitutive activity of the AR transcriptional program and a CRPC growth phenotype independent of full-length AR or androgens. These findings demonstrate that AR gene rearrangements are a unique resistance mechanism by which AR transcriptional activity can be uncoupled from endocrine regulation in CRPC. PMID:24101480

Transcriptional and posttranscriptional regulation of Bacillus sp. CDB3 arsenic-resistance operon ars1

PubMed Central

Yu, Xuefei; Zheng, Wei; Bhat, Somanath; Aquilina, J. Andrew

2015-01-01

Bacillus sp. CDB3 possesses a novel eight-gene ars cluster (ars1, arsRYCDATorf7orf8) with some unusual features in regard to expression regulation. This study demonstrated that the cluster is a single operon but can also produce a short three-gene arsRYC transcript. A hairpin structure formed by internal inverted repeats between arsC and arsD was shown to diminish the expression of the full operon, thereby probably acting as a transcription attenuator. A degradation product of the arsRYC transcript was also identified. Electrophoretic mobility shift analysis demonstrated that ArsR interacts with the ars1 promoter forming a protein-DNA complex that could be impaired by arsenite. However, no interaction was detected between ArsD and the ars1 promoter, suggesting that the CDB3 ArsD protein may not play a regulatory role. Compared to other ars gene clusters, regulation of the Bacillus sp. CDB3 ars1 operon is more complex. It represents another example of specific mRNA degradation in the transporter gene region and possibly the first case of attenuator-mediated regulation of ars operons. PMID:26355338

40Ar/36Ar analyses of historic lava flows

USGS Publications Warehouse

Dalrymple, G.B.

1969-01-01

The ratio 40Ar/36Ar was measured for 26 subaerial historic lava flows. Approximately one-third of the samples had 40Ar/36Ar ratios either higher or lower than the atmospheric value of 295.5 at the 95% confidence level. Excess radiogenic 40Ar in five flows ranged from about 1 ?? 10-13 to 1.5 ?? 10-12 mol/g. Possible excess 36Ar in three flows was on the order of 10-16 to 10-15 mol/g. Upper 95% confidence limits for excess 40Ar in samples with normal 40Ar/36Ar ratios are generally less than 3 ?? 10-13 mol/g. The origin of the excess 36Ar is unknown but it may be due either to the incorporation of primitive argon that has been stored in the mantle in very low potassium environments or to enrichment in 36Ar as atmospheric argon diffuses into the rocks after they cool. ?? 1969.

TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer

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

Kharlyngdoh, Joubert Banjop; Asnake, Solomon; Prad

Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the AR{sub T877A} mutation, which is frequently detected mutation in PCa tumors and the AR{sub W741C} that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide. AR activation by non-androgenic environmental substances has been suggested to affect PCa progression.more » In the present study we investigated the effect of AR mutations (AR{sub W741C} and AR{sub T877A}) on the transcriptional activation following exposure of cells to an androgenic brominated flame retardant, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH, also named DBE-DBCH). The AR mutations resulted in higher interaction energies and increased transcriptional activation in response to TBECH diastereomer exposures. The AR{sub T877A} mutation rendered AR highly responsive to low levels of DHT and TBECH and led to increased AR nuclear translocation. Gene expression analysis showed a stronger induction of AR target genes in LNCaP cells (AR{sub T877A}) compared to T-47D cells (AR{sub WT}) following TBECH exposure. Furthermore, AR knockdown experiments confirmed the AR dependency of these responses. The higher sensitivity of AR{sub T877A} and AR{sub W741C} to low levels of TBECH suggests that cells with these AR mutations are more susceptible to androgenic endocrine disrupters. - Highlights: • TBECH, is an endocrine disrupting compound that differ in activity depending on AR structure and sequence. • TBECH interaction with the human AR-LBD containing the mutations W741C and T877A is increased compared to the wild type receptor • The mutations, W741C and T877A, are more potent than the wild type receptor at inducing AR nuclear translocation and transcriptional activation following TBECH exposure. • TBECH mediates action on androgen response genes via AR signaling.« less

Both alpha(1A)- and alpha(1B)-adrenergic receptors crosstalk to down regulate beta(1)-ARs in mouse heart: coupling to differential PTX-sensitive pathways.

PubMed

Rorabaugh, Boyd R; Gaivin, Robert J; Papay, Robert S; Shi, Ting; Simpson, Paul C; Perez, Dianne M

2005-11-01

Adrenergic receptors (ARs) play an important role in the regulation of cardiac function. Cardiac inotropy is primarily regulated by beta(1)-ARs. However, alpha(1)-ARs may play an important role in inotropy during heart failure. Previous work has suggested that the alpha(1B)-AR modulates beta(1)-AR function in the heart. The potential role of the alpha(1A)-AR has not been previously studied. We used transgenic mice that express constitutively active mutant (CAM) forms of the alpha(1A)-AR or alpha(1B)-AR regulated by their endogenous promoters. Expression of the CAM alpha(1A)-AR or CAM alpha(1B)-AR had no effect on basal cardiac function (developed pressure, +dP/dT, -dP/dT, heart rate, flow rate). However, both alpha(1)-AR subtypes significantly decreased isoproterenol-stimulated +dP/dT. Pertussis toxin had no effect on +dP/dT in CAM alpha(1A)-AR hearts but restored +dP/dT to non-transgenic values in CAM alpha(1B)-AR hearts. Radioligand binding indicated a selective decrease in the density of beta(1)-ARs in both CAM mice. However, G-proteins, cAMP, or the percentage of high and low affinity states were unchanged in either transgenic compared with control. These data demonstrate that CAM alpha(1A)- and alpha(1B)-ARs both down regulate beta(1)-AR-mediated inotropy in the mouse heart. However, alpha(1)-AR subtypes are coupled to different beta-AR mediated signaling pathways with the alpha(1B)-AR being pertussis toxin sensitive.

Controlling Androgen receptor nuclear localization by dendrimer conjugates

NASA Astrophysics Data System (ADS)

Wang, Haoyu

Androgen Receptor (AR) antagonists, such as bicalutamide and flutamide have been used widely in the treatment of prostate cancer. Although initial treatment is effective, prostate cancer cells often acquire antiandrogen resistance with prolonged treatment. AR over-expression and AR mutations contribute to the development of antiandrogen resistant cancer. Second generation antiandrogens such as enzalutamide are more effective and show reduced AR nuclear localization. In this study, derivatives of PAN52, a small molecule antiandrogen previously developed in our lab, were conjugated to the surface of generation 4 and generation 6 PAMAM dendrimers to obtain antiandrogen PAMAM dendrimer conjugates (APDC). APDCs readily enter cells and associate with AR in the cytoplasm. Due to their large size and positive charge, they can not enter the nucleus, thus retaining AR in the cytoplasm. In addition, APDCs are effective in decreasing AR mediated transcription and cell proliferation. APDC is the first AR antagonists that inhibit DHT-induced nuclear localization of AR. By inhibiting AR nuclear localization, APDC represents a new class of antiandrogens that offer an alternative approach to addressing antiandrogen-resistant prostate cancer. Lysine post-translational modification of AR Nuclear Localization Sequence (NLS) has great impact on AR cellular localization. It is of interest to understand which modifications modulate AR translocation into the nucleus. In this study, we prepared dendrimer-based acetyltransferase mimetic (DATM), DATM is able to catalytically acetylate AR in CWR22Rv1 cells, which will be a useful tool for studying AR modification effect on AR cellular localization. Derivatives of DATM, which transfer other chemical groups to AR, can be prepared similarly, and with more dendrimer based AR modification tools prepared in future, we will be able to understand and control AR cellular localization through AR modification.

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction.

PubMed

Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao

2017-12-01

Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

Celastrol Induces Autophagy by Targeting AR/miR-101 in Prostate Cancer Cells

PubMed Central

Guo, Jianquan; Huang, Xuemei; Wang, Hui; Yang, Huanjie

2015-01-01

Autophagy is an evolutionarily conserved process responsible for the degradation and recycling of cytoplasmic components through autolysosomes. Targeting AR axis is a standard strategy for prostate cancer treatment; however, the role of AR in autophagic processes is still not fully understood. In the present study, we found that AR played a negative role in AR degrader celastrol-induced autophagy. Knockdown of AR in AR-positive prostate cancer cells resulted in enhanced autophagy. Ectopic expression of AR in AR-negative prostate cancer cells, or gain of function of the AR signaling in AR-positive cells, led to suppression of autophagy. Since miR-101 is an inhibitor of autophagy and its expression was decreased along with AR in the process of celastrol-induced autophagy, we hypothesize that AR inhibits autophagy through transactivation of miR-101. AR binding site was defined in the upstream of miR-101 gene by luciferase reporter and ChIP assays. MiR-101 expression correlated with AR status in prostate cancer cell lines. The inhibition of celastrol-induced autophagy by AR was compromised by blocking miR-101; while transfection of miR-101 led to inhibition of celastrol-induced autophagy in spite of AR depletion. Furthermore, mutagenesis of the AR binding site in miR-101 gene led to decreased suppression of autophagy by AR. Finally, autophagy inhibition by miR-101 mimic was found to enhance the cytotoxic effect of celastrol in prostate cancer cells. Our results demonstrate that AR inhibits autophagy via transactivation of miR-101, thus combination of miR-101 mimics with celastrol may represent a promising therapeutic approach for treating prostate cancer. PMID:26473737

Pulsations of the High-Amplitude δ Scuti star YZ Bootis

NASA Astrophysics Data System (ADS)

Yang, Tao-Zhi; Esamdin, Ali; Fu, Jian-Ning; Niu, Hu-Biao; Feng, Guo-Jie; Song, Fang-Fang; Liu, Jin-Zhong; Ma, Lu

2018-01-01

We present a study on pulsations of the high-amplitude δ Scuti star YZ Boo based on photometric observations in Johnson V and R bands with both the Nanshan 1-m telescope of Xinjiang AstronomicalObservatory (XAO) and the Xinglong 85-cmtelescope of NationalAstronomical Observatories, Chinese Academy of Sciences (NAOC). Fourier analysis of the light curves reveals the fundamental radial mode and its five harmonics, with the fourth and fifth being newly detected. Thirty-nine new times of maximum light are determined from the light curves, and combined with those in the literature, we construct the O ‑ C diagram, derive a new ephemeris and determine a new value for the updated period of 0.104091579(2). In addition, the O ‑ C diagram reveals an increasing rate of period change for YZ Boo. Theoretical models are calculated and constrained with the observationally determined parameters of YZ Boo. The mass and age of YZ Boo are hence derived as M = 1.61±0.05 M ⊙ and age = (1.44±0.14)×109 yr, respectively.With both the frequency of the fundamental radial mode and the rate of period change, YZ Boo is located at the post main sequence stage.

On the Radii of Close-in Giant Planets.

PubMed

Burrows; Guillot; Hubbard; Marley; Saumon; Lunine; Sudarsky

2000-05-01

The recent discovery that the close-in extrasolar giant planet HD 209458b transits its star has provided a first-of-its-kind measurement of the planet's radius and mass. In addition, there is a provocative detection of the light reflected off of the giant planet tau Bootis b. Including the effects of stellar irradiation, we estimate the general behavior of radius/age trajectories for such planets and interpret the large measured radii of HD 209458b and tau Boo b in that context. We find that HD 209458b must be a hydrogen-rich gas giant. Furthermore, the large radius of a close-in gas giant is not due to the thermal expansion of its atmosphere but to the high residual entropy that remains throughout its bulk by dint of its early proximity to a luminous primary. The large stellar flux does not inflate the planet but retards its otherwise inexorable contraction from a more extended configuration at birth. This implies either that such a planet was formed near its current orbital distance or that it migrated in from larger distances (>/=0.5 AU), no later than a few times 107 yr of birth.

An expert computer program for classifying stars on the MK spectral classification system

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

Gray, R. O.; Corbally, C. J.

2014-04-01

This paper describes an expert computer program (MKCLASS) designed to classify stellar spectra on the MK Spectral Classification system in a way similar to humans—by direct comparison with the MK classification standards. Like an expert human classifier, the program first comes up with a rough spectral type, and then refines that spectral type by direct comparison with MK standards drawn from a standards library. A number of spectral peculiarities, including barium stars, Ap and Am stars, λ Bootis stars, carbon-rich giants, etc., can be detected and classified by the program. The program also evaluates the quality of the delivered spectralmore » type. The program currently is capable of classifying spectra in the violet-green region in either the rectified or flux-calibrated format, although the accuracy of the flux calibration is not important. We report on tests of MKCLASS on spectra classified by human classifiers; those tests suggest that over the entire HR diagram, MKCLASS will classify in the temperature dimension with a precision of 0.6 spectral subclass, and in the luminosity dimension with a precision of about one half of a luminosity class. These results compare well with human classifiers.« less

Making the optimal decision in selecting protective clothing

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

Price, J. Mark

2007-07-01

Protective Clothing plays a major role in the decommissioning and operation of nuclear facilities. Literally thousands of employee dress-outs occur over the life of a decommissioning project and during outages at operational plants. In order to make the optimal decision on which type of protective clothing is best suited for the decommissioning or maintenance and repair work on radioactive systems, a number of interrelating factors must be considered, including - Protection; - Personnel Contamination; - Cost; - Radwaste; - Comfort; - Convenience; - Logistics/Rad Material Considerations; - Reject Rate of Laundered Clothing; - Durability; - Security; - Personnel Safety includingmore » Heat Stress; - Disposition of Gloves and Booties. In addition, over the last several years there has been a trend of nuclear power plants either running trials or switching to Single Use Protective Clothing (SUPC) from traditional protective clothing. In some cases, after trial usage of SUPC, plants have chosen not to switch. In other cases after switching to SUPC for a period of time, some plants have chosen to switch back to laundering. Based on these observations, this paper reviews the 'real' drivers, issues, and interrelating factors regarding the selection and use of protective clothing throughout the nuclear industry. (authors)« less

β-Adrenergic Receptor-Mediated Cardiac Contractility is Inhibited via Vasopressin Type 1A-Receptor-Dependent Signaling

PubMed Central

Tilley, Douglas G.; Zhu, Weizhong; Myers, Valerie D.; Barr, Larry A.; Gao, Erhe; Li, Xue; Song, Jianliang; Carter, Rhonda L.; Makarewich, Catherine A.; Yu, Daohai; Troupes, Constantine D.; Grisanti, Laurel A.; Coleman, Ryan C.; Koch, Walter J.; Houser, Steven R.; Cheung, Joseph Y.; Feldman, Arthur M.

2014-01-01

Background Enhanced arginine vasopressin (AVP) levels are associated with increased mortality during end-stage human heart failure (HF), and cardiac AVP type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulated βAR responsiveness and in doing so contributes to HF development. Methods and Results Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca2+ mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein-independent/GRK-dependent manner. Conclusions This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated HF and elevated AVP. PMID:25205804

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

Aciego, S.M.; Jourdan, F.; DePaolo, D.J.

Late Quaternary, post-shield lavas from the Mauna Kea and Kohala volcanoes on the Big Island of Hawaii have been dated using the {sup 40}Ar/{sup 39}Ar and U-Th/He methods. The objective of the study is to compare the recently demonstrated U-Th/He age method, which uses basaltic olivine phenocrysts, with {sup 40}Ar/{sup 39}Ar ages measured on groundmass from the same samples. As a corollary, the age data also increase the precision of the chronology of volcanism on the Big Island. For the U-Th/He ages, U, Th and He concentrations and isotopes were measured to account for U-series disequilibrium and initial He. Singlemore » analyses U-Th/He ages for Hamakua lavas from Mauna Kea are 87 {+-} 40 ka to 119 {+-} 23 ka (2{sigma} uncertainties), which are in general equal to or younger than {sup 40}Ar/{sup 39}Ar ages. Basalt from the Polulu sequence on Kohala gives a U-Th/He age of 354 {+-} 54 ka and a {sup 40}Ar/{sup 39}Ar age of 450 {+-} 40 ka. All of the U-Th/He ages, and all but one spurious {sup 40}Ar/{sup 39}Ar ages conform to the previously proposed stratigraphy and published {sup 14}C and K-Ar ages. The ages also compare favorably to U-Th whole rock-olivine ages calculated from {sup 238}U - {sup 230}Th disequilibria. The U-Th/He and {sup 40}Ar/{sup 39}Ar results agree best where there is a relatively large amount of radiogenic {sup 40}Ar (>10%), and where the {sup 40}Ar/{sup 36}Ar intercept calculated from the Ar isochron diagram is close to the atmospheric value. In two cases, it is not clear why U-Th/He and {sup 40}Ar/{sup 39}Ar ages do not agree within uncertainty. U-Th/He and {sup 40}Ar/{sup 39}Ar results diverge the most on a low-K transitional tholeiitic basalt with abundant olivine. For the most alkalic basalts with negligible olivine phenocrysts, U-Th/He ages were unattainable while {sup 40}Ar/{sup 39}Ar results provide good precision even on ages as low as 19 {+-} 4 ka. Hence, the strengths and weaknesses of the U-Th/He and {sup 40}Ar/{sup 39}Ar methods are complimentary for basalts with ages of order 100-500 ka.« less

Androgen receptor polyglutamine repeat length affects receptor activity and C2C12 cell development.

PubMed

Sheppard, Ryan L; Spangenburg, Espen E; Chin, Eva R; Roth, Stephen M

2011-10-20

Testosterone (T) has an anabolic effect on skeletal muscle and is believed to exert its local effects via the androgen receptor (AR). The AR harbors a polymorphic stretch of glutamine repeats demonstrated to inversely affect receptor transcriptional activity in prostate and kidney cells. The effects of AR glutamine repeat length on skeletal muscle are unknown. In this study we examined the effect of AR CAG repeat length on AR function in C2C12 cells. AR expression vectors harboring 14, 24, and 33 CAG repeats were used to assess AR transcriptional activity. C2C12 cell proliferation, differentiation, gene expression, myotube formation, and myonuclear fusion index were assessed. Transcriptional activity increased with increasing repeat length and in response to testosterone (AR14 = 3.91 ± 0.26, AR24 = 25.21 ± 1.72, AR33 = 36.08 ± 3.22 relative light units; P < 0.001). Ligand activation was increased for AR33 (2.10 ± 0.04) compared with AR14 (1.54 ± 0.09) and AR24 (1.57 ± 0.05, P < 0.001). AR mRNA expression was elevated in each stably transfected line. AR33 cell proliferation (20,512.3 ± 1,024.0) was decreased vs. AR14 (27,604.17 ± 1,425.3; P < 0.001) after 72 h. Decreased CK activity in AR14 cells (54.9 ± 2.9 units/μg protein) in comparison to AR33 (70.8 ± 8.1) (P < 0.05) was noted. The myonuclear fusion index was lower for AR14 (15.21 ± 3.24%) and AR33 (9.97 ± 3.14%) in comparison to WT (35.07 ± 5.60%, P < 0.001). AR14 and AR33 cells also displayed atypical myotube morphology. RT-PCR revealed genotype differences in myostatin and myogenin expression. We conclude that AR polyglutamine repeat length is directly associated with transcriptional activity and alters the growth and development of C2C12 cells. This polymorphism may contribute to the heritability of muscle mass in humans.

The effect of SEM imaging on the Ar/Ar system in feldspars

NASA Astrophysics Data System (ADS)

Flude, S.; Sherlock, S.; Lee, M.; Kelley, S. P.

2010-12-01

Complex microtextures form in K-feldspar crystals as they cool and are affected by deuteric alteration. This complex structure is the cause of variable closure temperatures for Ar-Ar, a phenomenon which has been utilized in multi domain diffusion (MDD) modelling to recover thermal histories [1]. However, there has been substantial controversy regarding the precise interaction between feldspar microtextures and Ar-diffusion [2,3]. A number of studies have addressed this issue using coupled SEM imaging and Ar/Ar UV laser ablation microprobe (UV-LAMP) analysis on the same sample, to enable direct comparison of microtextures with Ar/Ar age data [4]. Here we have tested the idea that SEM work may affect Ar/Ar ages, leading to inaccurate results in subsequent Ar/Ar analyses. Three splits of alkali feldspar from the Dartmoor Granite in SW England were selected for Ar/Ar UV-LAMP analysis. Split 1 (“control”) was prepared as a polished thick section for Ar/Ar analysis. Split 2 (“SEM”) was prepared as a polished thick section, was chemically-mechanically polished with colloidal silica and underwent SEM imaging (uncoated) and focussed ion beam (FIB) milling (gold coated); electron beam damage in the SEM was maximised by leaving the sample at high magnification for eight minutes. Split 3 (“Etch”) is a cleavage fragment that was etched with HF vapour and underwent low to moderate magnification SEM imaging. The control split gave a range of laser-spot ages consistent with the expected cooling age of the granite and high yields of radiogenic 40Ar* (>90%). The area of the “SEM” split that experienced significant electron beam damage gave younger than expected ages and 40Ar* yields as low as 57%. These are interpreted as a combination of implantation of atmospheric Ar and local redistribution of K within the sample. The area of “SEM” that underwent FIB milling gave ages and 40Ar* yields comparable to the control split, suggesting that the Au-coat minimises FIB damage and that colloidal-polishing and low-magnification SEM imaging do not affect the Ar/Ar system. The “Etch” split gave younger than expected ages and 40Ar* yields as low as 58%, suggesting that HF etching also disrupts the Ar/Ar system. These results suggest that SEM techniques involving intense electron bombardment of an uncoated sample, such as charge contrast imaging and electron backscatter diffraction (EBSD), may disrupt the Ar/Ar system in the sample, leading to spurious results. Etching samples with HF, as is often done for routine Ar/Ar preparation of volcanic phenocrysts, introduces atmospheric Ar and may result in differential loss or gain of K and Ar isotopes, leading to spurious results. References [1] Lovera and Richter, 1989, J. Geophys. Res. 94, 17917-17935. [2] Parsons. et al., 1999, Cont. Min. Pet. 136, 92-110. [3] Mark et al., 2008, Geochim. Cosmochim. Acta, 72 2695-2710. [4] Reddy et al., 2001, Cont. Min. Pet., 141 186-200.

Influence of Feedstock Powder Modification by Heat Treatments on the Properties of APS-Sprayed Al2O3-40% TiO2 Coatings

NASA Astrophysics Data System (ADS)

Berger, Lutz-Michael; Sempf, Kerstin; Sohn, Yoo Jung; Vaßen, Robert

2018-04-01

The formation and decomposition of aluminum titanate (Al2TiO5, tialite) in feedstock powders and coatings of the binary Al2O3-TiO2 system are so far poorly understood. A commercial fused and crushed Al2O3-40%TiO2 powder was selected as the feedstock for the experimental series presented in this paper, as the composition is close to that of Al2TiO5. Part of that powder was heat-treated in air at 1150 and 1500 °C in order to modify the phase composition, while not influencing the particle size distribution and processability. The powders were analyzed by thermal analysis, XRD and FESEM including EDS of metallographically prepared cross sections. Only a maximum content of about 45 wt.% Al2TiO5 was possible to obtain with the heat treatment at 1500 °C due to inhomogeneous distribution of Al and Ti in the original powder. Coatings were prepared by plasma spraying using a TriplexPro-210 (Oerlikon Metco) with Ar-H2 and Ar-He plasma gas mixtures at plasma power levels of 41 and 48 kW. Coatings were studied by XRD, SEM including EDS linescans of metallographically prepared cross sections, and microhardness HV1. With the exception of the powder heat-treated at 1500 °C an Al2TiO5-Ti3O5 (tialite-anosovite) solid solution Al2- x Ti1+ x O5 instead of Al2TiO5 existed in the initial powder and the coatings.

Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription*

PubMed Central

Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Lee, Jinhee; Wright, Michael E.

2016-01-01

Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the “AR-interactome.” Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers. PMID:27365400

Heterodimerization with beta2-adrenergic receptors promotes surface expression and functional activity of alpha1D-adrenergic receptors.

PubMed

Uberti, Michelle A; Hague, Chris; Oller, Heide; Minneman, Kenneth P; Hall, Randy A

2005-04-01

The alpha1D-adrenergic receptor (alpha1D-AR) is a G protein-coupled receptor (GPCR) that is poorly trafficked to the cell surface and largely nonfunctional when heterologously expressed by itself in a variety of cell types. We screened a library of approximately 30 other group I GPCRs in a quantitative luminometer assay for the ability to promote alpha1D-AR cell surface expression. Strikingly, these screens revealed only two receptors capable of inducing robust increases in the amount of alpha1D-AR at the cell surface: alpha1B-AR and beta2-AR. Confocal imaging confirmed that coexpression with beta2-AR resulted in translocation of alpha1D-AR from intracellular sites to the plasma membrane. Additionally, coimmunoprecipitation studies demonstrated that alpha1D-AR and beta2-AR specifically interact to form heterodimers when coexpressed in HEK-293 cells. Ligand binding studies revealed an increase in total alpha1D-AR binding sites upon coexpression with beta2-AR, but no apparent effect on the pharmacological properties of the receptors. In functional studies, coexpression with beta2-AR significantly enhanced the coupling of alpha1D-AR to norepinephrine-stimulated Ca2+ mobilization. Heterodimerization of beta2-AR with alpha1D-AR also conferred the ability of alpha1D-AR to cointernalize upon beta2-AR agonist stimulation, revealing a novel mechanism by which these different adrenergic receptor subtypes may regulate each other's activity. These findings demonstrate that the selective association of alpha1D-AR with other receptors is crucial for receptor surface expression and function and also shed light on a novel mechanism of cross talk between alpha1- and beta2-ARs that is mediated through heterodimerization and cross-internalization.

Cooperative Dynamics of AR and ER Activity in Breast Cancer

PubMed Central

D’Amato, Nicholas C.; Gordon, Michael A.; Babbs, Beatrice L.; Spoelstra, Nicole S.; Carson Butterfield, Kiel T.; Torkko, Kathleen C.; Phan, Vernon T.; Barton, Valerie N.; Rogers, Thomas J.; Sartorius, Carol A; Elias, Anthony D.; Gertz, Jason; Jacobsen, Britta M.; Richer, Jennifer K.

2016-01-01

Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha positive (ER+) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared to dihydrotestosterone (DHT). Estradiol-induced AR binding sites were enriched for estrogen response elements and had significant overlap with ER binding sites. Furthermore, AR inhibition reduced baseline and estradiol-mediated proliferation in multiple ER+/AR+ breast cancer cell lines, and synergized with tamoxifen and fulvestrant. In vivo, enzalutamide significantly reduced viability of tamoxifen-resistant MCF7 xenograft tumors and an ER+/AR+ patient-derived model. Enzalutamide also reduced metastatic burden following cardiac injection. Lastly, in a comparison of ER+/AR+ primary tumors versus patient-matched local recurrences or distant metastases, AR expression was often maintained even when ER was reduced or absent. These data provide pre-clinical evidence that anti-androgens that inhibit AR nuclear localization affect both AR and ER, and are effective in combination with current breast cancer therapies. In addition, single agent efficacy may be possible in tumors resistant to traditional endocrine therapy, since clinical specimens of recurrent disease demonstrate AR expression in tumors with absent or refractory ER. Implications This study suggests that AR plays a previously-unrecognized role in supporting E2-mediated ER activity in ER+/AR+ breast cancer cells, and that enzalutamide may be an effective therapeutic in ER+/AR+ breast cancers. PMID:27565181

Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo

PubMed Central

Kwegyir-Afful, Andrew K.; Ramalingam, Senthilmurugan; Purushottamachar, Puranik; Ramamurthy, Vidya P.; Njar, Vincent C.O.

2015-01-01

Galeterone (Gal) is a first-in-class multi-target oral small molecule that will soon enter pivotal phase III clinical trials in castration resistant prostate cancer (CRPC) patients. Gal disrupts androgen receptor (AR) signaling via inhibition of CYP17, AR antagonism and AR degradation. Resistance to current therapy is attributed to up-regulation of full-length AR (fAR), splice variants AR (AR-Vs) and AR mutations. The effects of gal and VNPT55 were analyzed on f-AR and AR-Vs (AR-V7/ARv567es) in LNCaP, CWR22Rv1 and DU145 (transfected with AR-Vs) human PC cells in vitro and CRPC tumor xenografts. Galeterone/VNPT55 decreased fAR/AR-V7 mRNA levels and implicates Mdm2/CHIP enhanced ubiquitination of posttranslational modified receptors, targeting them for proteasomal degradation. Gal and VNPT55 also induced significant apoptosis in PC cells via increased Bax/Bcl2 ratio, cytochrome-c release with concomitant cleavage of caspase 3 and PARP. More importantly, gal and VNPT55 exhibited strong in vivo anti-CRPC activities, with no apparent host toxicities. This study demonstrate that gal and VNPT55 utilize cell-based mechanisms to deplete both fAR and AR-Vs. Importantly, the preclinical activity profiles, including profound apoptotic induction and inhibition of CRPC xenografts suggest that these agents offer considerable promise as new therapeutics for patients with CRPC and those resistant to current therapy. PMID:26196320

Histone demethylase JMJD1A promotes alternative splicing of AR variant 7 (AR-V7) in prostate cancer cells.

PubMed

Fan, Lingling; Zhang, Fengbo; Xu, Songhui; Cui, Xiaolu; Hussain, Arif; Fazli, Ladan; Gleave, Martin; Dong, Xuesen; Qi, Jianfei

2018-05-15

Formation of the androgen receptor splicing variant 7 (AR-V7) is one of the major mechanisms by which resistance of prostate cancer to androgen deprivation therapy occurs. The histone demethylase JMJD1A (Jumonji domain containing 1A) functions as a key coactivator for AR by epigenetic regulation of H3K9 methylation marks. Here, we describe a role for JMJD1A in AR-V7 expression. While JMJD1A knockdown had no effect on full-length AR (AR-FL), it reduced AR-V7 levels in prostate cancer cells. Reexpression of AR-V7 in the JMJD1A-knockdown cells elevated expression of select AR targets and partially rescued prostate cancer cell growth in vitro and in vivo. The AR-V7 protein level correlated positively with JMJD1A in a subset of human prostate cancer specimens. Mechanistically, we found that JMJD1A promoted alternative splicing of AR-V7 through heterogeneous nuclear ribonucleoprotein F (HNRNPF), a splicing factor known to regulate exon inclusion. Knockdown of JMJD1A or HNRNPF inhibited splicing of AR-V7, but not AR-FL, in a minigene reporter assay. JMJD1A was found to interact with and promote the recruitment of HNRNPF to a cryptic exon 3b on AR pre-mRNA for the generation of AR-V7. Taken together, the role of JMJD1A in AR-FL coactivation and AR-V7 alternative splicing highlights JMJD1A as a potentially promising target for prostate cancer therapy.

Differential regulation of metabolic pathways by androgen receptor (AR) and its constitutively active splice variant, AR-V7, in prostate cancer cells

PubMed Central

Shafi, Ayesha A.; Putluri, Vasanta; Arnold, James M.; Tsouko, Efrosini; Maity, Suman; Roberts, Justin M.; Coarfa, Cristian; Frigo, Daniel E.; Putluri, Nagireddy; Sreekumar, Arun; Weigel, Nancy L.

2015-01-01

Metastatic prostate cancer (PCa) is primarily an androgen-dependent disease, which is treated with androgen deprivation therapy (ADT). Tumors usually develop resistance (castration-resistant PCa [CRPC]), but remain androgen receptor (AR) dependent. Numerous mechanisms for AR-dependent resistance have been identified including expression of constitutively active AR splice variants lacking the hormone-binding domain. Recent clinical studies show that expression of the best-characterized AR variant, AR-V7, correlates with resistance to ADT and poor outcome. Whether AR-V7 is simply a constitutively active substitute for AR or has novel gene targets that cause unique downstream changes is unresolved. Several studies have shown that AR activation alters cell metabolism. Using LNCaP cells with inducible expression of AR-V7 as a model system, we found that AR-V7 stimulated growth, migration, and glycolysis measured by ECAR (extracellular acidification rate) similar to AR. However, further analyses using metabolomics and metabolic flux assays revealed several differences. Whereas AR increased citrate levels, AR-V7 reduced citrate mirroring metabolic shifts observed in CRPC patients. Flux analyses indicate that the low citrate is a result of enhanced utilization rather than a failure to synthesize citrate. Moreover, flux assays suggested that compared to AR, AR-V7 exhibits increased dependence on glutaminolysis and reductive carboxylation to produce some of the TCA (tricarboxylic acid cycle) metabolites. These findings suggest that these unique actions represent potential therapeutic targets. PMID:26378018

Extraction, fractionation and re-fractionation of Artemisia nilagirica for anticancer activity and HPLC-ESI-QTOF-MS/MS determination.

PubMed

Sahu, Neha; Meena, Sanjeev; Shukla, Vijaya; Chaturvedi, Priyank; Kumar, Brijesh; Datta, Dipak; Arya, K R

2018-03-01

Medicinal plants used in traditional medicines are affordable, easily accessible, safer, less toxic and considered as a rich or efficient source of bioactive molecules for modern therapeutics. Artemisia nilagirica (AR) has a long history of use in Indian traditional medicine to combat a wide variety of diseases including cancer. Considering the vast potential of traditional healing plants to deliver safer, less toxic and efficient chemotherapeutics, we have examined anticancer activity of ethanolic extract, bioactive fractions and sub-fractions of AR against different human cancer cell lines along with their phytochemical analysis to understand the insights of novel anticancer activities for further preclinical studies. Fresh plant material of AR was procured from the wild, dried and ground. The grinded materials was extracted in ethanol (AR-01) and fractionated into butanol (AR-02), ethyl acetate (AR-03), hexane (AR-04) and water (AR-05). The cytotoxicity was evaluated against three different human cancer cell lines, i.e. colon (DLD-1), lung (A-549), and breast (MCF-7) using Sulforhodamine B (SRB) assay along with non-cancerous VERO cells as control and doxorubicin (DOX) as positive control. As we observed strong cytotoxicity of AR-03 and AR-04 fractions against tested cells and marked cytotoxic effects particularly in colon cancer cell lines, we further re-fractionated, AR-03 into (AR-03A, AR-03B, AR-03C, AR-03D, AR-03E) and AR-04 into (AR-04A, AR-04B, AR-04C) sub-fractions by column chromatography and investigated against the same panel of cell lines in addition to one more colon cancer cell line (HT-29). Phytochemical analysis was performed through HPLC-ESI-QTOF-MS/MS fragmentation. Ethyl acetate (AR-03) and hexane (AR-04) fractions were found to be the most cytotoxic against all the tested cell lines. Further, AR-03E and AR-04A sub-fractions were found more specific cytotoxic selectively against DLD-1 cancer cell lines at 100µg/ml concentration. HPLC-ESI-QTOF-MS/MS determination revealed the presence of 17 compounds in AR-01. Among them, 4 compounds were reported for the first time in this species. However, 3 identified compounds (artemorin, β-santonin and caryophyllene oxide) in AR-03E sub-fraction were commonly present in each bioactive fraction and may be considered as potential and safest cytotoxic agents for anticancer activity. Experimental evidences reported in this paper for anticancer activity validate the traditional wisdom of Artemisia nilagirica as an anticancer herbal drug. To our knowledge, this is our first novel observation of cytotoxicity and selectivity of ethyl acetate and hexane sub-fraction of AR-01 i.e. AR-03E and AR-04A respectively against DLD-1 human cancer cell lines. HPLC-ESI-QTOF-MS/MS determination attributes the identification of cytotoxic compounds which may be used for further preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies

PubMed Central

Chan, Siu Chiu; Selth, Luke A.; Li, Yingming; Nyquist, Michael D.; Miao, Lu; Bradner, James E.; Raj, Ganesh V.; Tilley, Wayne D.; Dehm, Scott M.

2015-01-01

Androgen receptor (AR) variants (AR-Vs) expressed in prostate cancer (PCa) lack the AR ligand binding domain (LBD) and function as constitutively active transcription factors. AR-V expression in patient tissues or circulating tumor cells is associated with resistance to AR-targeting endocrine therapies and poor outcomes. Here, we investigated the mechanisms governing chromatin binding of AR-Vs with the goal of identifying therapeutic vulnerabilities. By chromatin immunoprecipitation and sequencing (ChIP-seq) and complementary biochemical experiments, we show that AR-Vs display a binding preference for the same canonical high-affinity androgen response elements (AREs) that are preferentially engaged by AR, albeit with lower affinity. Dimerization was an absolute requirement for constitutive AR-V DNA binding and transcriptional activation. Treatment with the bromodomain and extraterminal (BET) inhibitor JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo. Importantly, this was associated with a novel JQ1 action of down-regulating AR-V transcript and protein expression. Overall, this study demonstrates that AR-Vs broadly restore AR chromatin binding events that are otherwise suppressed during endocrine therapy, and provides pre-clinical rationale for BET inhibition as a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa. PMID:25908785

40Ar/39Ar Dating of Volcanic Glass

NASA Astrophysics Data System (ADS)

Morgan, L. E.; Renne, P. R.; Watkins, J. M.

2007-12-01

Application of the 40Ar/39Ar method to volcanic glasses has been somewhat stigmatized following several studies demonstrating secondary mobility of K and Ar. Much of the stigma is unwarranted, however, since most studies only impugned the reliability of the K-Ar and 40Ar/39Ar techniques when applied to glass shards rather than obsidian clasts with low surface area to volume ratios. We provide further evidence for problematic K loss and/or 39Ar recoil ejection from glass shards in 40Ar/39Ar step heating results for comagmatic feldspars and shards. In an extreme case, the plateau age of the feldspars (0.17 ± 0.03 Ma at 2σ) is significantly younger than the plateau age of the glass (0.85 ± 0.05 Ma at 2σ). If the feldspar age is reasonably interpreted as the eruption age of the ash, it is likely that the glass shards experienced K and/or 39Ar loss. Electron microprobe analyses of the glass shards have low totals (~93%) and no systematic lateral variability (i.e., diffusion gradients) in K, suggesting that the lengthscale of the glass shards is smaller than the lengthscale of K diffusion. Obsidian clasts should not be as susceptible to K loss since any hydrated (K-depleted) volume represents a small fraction of the total material and can often be physically removed prior to analysis. Samples described here are detrital obsidian clasts from the Afar region of Ethiopia. Evidence from Fourier Transform Infrared Spectroscopy (FTIR), and previous work by Anovitz (1999), confirm that the scale of water and potassium mobility are often small in comparison to the size of obsidian clasts but large enough to effect the bulk composition of glass shards. This expectation is confirmed in another tuff wherein comagmatic obsidian clasts and sanidine phenocrysts yield indistinguishable 40Ar/39Ar ages of 4.4 Ma High abundances of non-radiogenic 40Ar, and kinetic fractionation of Ar isotopes during quenching and/or laboratory degassing resulting in incomplete equilibration between atmospheric and magmatic argon, may also hinder accurate 40Ar/39Ar geochronology of volcanic glasses. Clasts derived from single flows (as determined by extrusion age and trace element geochemistry) display variations as much as 3-4 orders of magnitude in atmospheric 40Ar concentrations. The clasts were likely sourced from different parts of the flows with varying proximity to the surface and thus differing thermal and atmospheric uptake histories. Because radiogenic and non-radiogenic components of 40Ar are energetically indistinct in glass, most samples fail to yield isochrons due to limited range in 40Ar: 39Ar: 36Ar. Most yield plateau ages, whose validity rests on the assumption of atmospheric initial 40Ar/36Ar. Some samples yield inverse isochrons with sub-atmospheric 40Ar/36Ar intercepts; unirradiated subsamples of these same samples also have sub-atmospheric 38Ar/36Ar ratios that are too high to be explained by mass fractionation. While the effects of non-radiogenic 40Ar remain poorly understood, this sample set yielded 32 out of 41 clasts having plateau and isochron ages within 2σ error of each other, and potentially problematic samples are generally identified with non-atmospheric isochron 40Ar/36Ar intercepts.

Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells

PubMed Central

Bolton, Eric C.

2015-01-01

The androgen receptor (AR) mediates the developmental, physiologic, and pathologic effects of androgens including 5α-dihydrotestosterone (DHT). However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti-AR), and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S-phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK) complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation. PMID:26372468

40Ar/39Ar and unspiked 40K-40Ar dating of upper Pleistocene volcanic activity in the Bas-Vivarais (Ardèche, France)

NASA Astrophysics Data System (ADS)

Sasco, Romain; Guillou, Hervé; Nomade, Sébastien; Scao, Vincent; Maury, René C.; Kissel, Catherine; Wandres, Camille

2017-07-01

Fifteen basanitic and tephritic flows from Bas-Vivarais, the youngest volcanic field in the French Massif Central together with the Chaîne des Puys, were dated by 40Ar/39Ar and 40K-40Ar on separated groundmass, and studied for paleomagnetism. An almost systematic discrepancy between the two types of ages is observed, the 40K-40Ar method providing ages up to 8.5 times the 40Ar/39Ar ones. Microscopic observations and geochemical analyses lead us to conclude that most of the K-Ar ages measured on Bas-Vivarais samples are in error due to extraneous argon originating from contamination by xenocrysts from disintegrated crustal and mantle xenoliths. However, 40Ar/39Ar experiments do not evidence any excess argon, suggesting two possibilities: 1, the extraneous argon contribution was eliminated during the pre-degassing of the samples at 600 °C prior to the step heating experiments, 2 - K-Ar ages may be older because larger quantities of xenocrysts, potential carriers of extraneous argon were involved in the K-Ar experiments than in the 40Ar/39Ar ones. 40Ar/39Ar ages are thus little or not affected by contamination and provide reliable ages for the studied volcanoes. Combined 40Ar/39Ar datings and magnetic directions for each flow point out to three successive stages in the volcanic evolution of Bas-Vivarais. Stage 1, limited to the northern part of the field, has a mean age of 187.3 ± 19.0 ka. In its southern part, Stages 2 and 3 emplaced magmas at 31.1 ± 3.9 ka and 23.9 ± 8.1 ka, respectively. These two last stages are consistent with available 14C dates but not with previous thermoluminescence data.

In situ dating on Mars: A new approach to the K–Ar method utilizing cosmogenic argon

DOE PAGES

Cassata, William S.

2013-08-22

In this paper, cosmogenic argon isotopes are produced in feldspars via nuclear reactions between cosmic rays and Ca and K atoms within the lattice. These cosmogenic isotopes can be used as proxies for K and Ca, much like nuclear reactor-derived 39Ar and 37Ar are used as proxies for K and Ca, respectively, in 40Ar/ 39Ar geochronology. If Ca and K are uniformly distributed, then the ratio of radiogenic 40Ar ( 40Ar*) to cosmogenic 38Ar or 36Ar ( 38Ar cos or 36Ar cos) is proportional to the difference between the radioisotopic and exposure ages, as well as the K/Ca ratio ofmore » the degassing phase. Thus cosmogenic, radiogenic, and trapped Ar isotopes, all of which can be measured remotely and are stable over geologic time, are sufficient to generate an isochron-like diagram from which the isotopic composition of the trapped component may be inferred. Finally, such data also provide a means to assess the extent to which the system has remained closed with respect to 40Ar*, thereby mitigating otherwise unquantifiable uncertainties that complicate the conventional K–Ar dating method.« less

Establishment of a novel immortalized human prostatic epithelial cell line stably expressing androgen receptor and its application for the functional screening of androgen receptor modulators

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

Yu, Shan; Wang, Ming-Wei; Yao, Xiaoqiang

2009-05-15

In this study, we developed a human prostatic epithelial cell line BPH-1-AR stably expressing AR by lentiviral transduction. Characterization by immunoblot and RT-PCR showed that AR was stably expressed in all representative BPH-1-AR clones. Androgen treatment induced a secretory differentiation phenotype in BPH-1-AR cells but suppressed their cell proliferation. Treatments with AR agonists induced transactivation of a transfected PSA-gene promoter reporter in BPH-1-AR cells, whereas this transactivation was suppressed by an AR antagonist flutamide, indicating that the transduced AR in BPH-1-AR cells was functional. Finally, we utilized BPH-1-AR cells to evaluate the androgenic activities and growth effects of five newlymore » developed non-steroidal compounds. Results showed that these compounds showed androgenic activities and growth-inhibitory effects on BPH-1-AR cells. Our results showed that BPH-1-AR cell line would be a valuable in vitro model for the study of androgen-regulated processes in prostatic epithelial cells and identification of compounds with AR-modulating activities.« less

Re-Evaluation of Ar-39 - Ar-40 Ages for Apollo Lunar Rocks 15415 and 60015

NASA Technical Reports Server (NTRS)

Park, J.; Nyquist, L. E.; Bogard, D. D.; Garrison, D. H.; Shih, C.-Y.

2010-01-01

We re-analyzed 39Ar-40Ar ages of Apollo lunar highland samples 15415 and 60015, two ferroan anorthosites analyzed previously in the 1970 s, with a more detailed approach and with revised decay constants. From these samples we carefully prepared 100-200 mesh mineral separates for analysis at the Noble Gas Laboratory at NASA-Johnson Space Center. The Ar-39-Ar-40 age spectra for 15415 yielded an age of 3851 +/- 38 Ma with 33-99% of Ar39 release, roughly in agreement with previously reported Ar-Ar ages. For 60015, we obtained an age of 3584 +/- 152 Ma in 23-98% of Ar39 release, also in agreement with previously reported Ar-Ar ages of approximately 3.5 Ga. Highland anorthosites like these are believed by many to be the original crust of the moon, formed by plagioclase floatation atop a magma ocean, however the Ar-Ar ages of 15415 and 60015 are considerably younger than lunar crust formation. By contrast, recently recovered lunar anorthosites such as Dhofar 489, Dhofar 908, and Yamato 86032 yield older Ar-Ar ages, up to 4.35 Ga, much closer to time of formation of the lunar crust. It follows that the Ar-Ar ages of the Apollo samples must have been reset by secondary heating, and that this heating affected highland anorthosites at both the Apollo 15 and Apollo 16 landing sites but did not affect lunar highland meteorites. One obvious consideration is that while the Apollo samples were collected from the near side of the moon, these lunar meteorites are thought to have originated from the lunar far side

Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors.

PubMed

Sun, D; Samuelson, L C; Yang, T; Huang, Y; Paliege, A; Saunders, T; Briggs, J; Schnermann, J

2001-08-14

Adenosine is a determinant of metabolic control of organ function increasing oxygen supply through the A2 class of adenosine receptors and reducing oxygen demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence was deleted by homologous recombination. Homozygous A1AR mutants that do not express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and without gross anatomical abnormalities. Plasma and urinary electrolytes were not different between genotypes. Likewise, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR(+/+), A1AR(+/-), and A1AR(-/-) mice. TGF responses to an increase in loop of Henle flow rate from 0 to 30 nl/min, whether determined as change of stop flow pressure or early proximal flow rate, were completely abolished in A1AR(-/-) mice (stop flow pressure response, -6.8 +/- 0.55 mmHg and -0.4 +/- 0.2 in A1AR(+/+) and A1AR(-/-) mice; early proximal flow rate response, -3.4 +/- 0.4 nl/min and +0.02 +/- 0.3 nl/min in A1AR(+/+) and A1AR(-/-) mice). Absence of TGF responses in A1AR-deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues.

Androgen receptor splice variants circumvent AR blockade by microtubule-targeting agents

PubMed Central

Zhang, Guanyi; Liu, Xichun; Li, Jianzhuo; Ledet, Elisa; Alvarez, Xavier; Qi, Yanfeng; Fu, Xueqi; Sartor, Oliver; Dong, Yan; Zhang, Haitao

2015-01-01

Docetaxel-based chemotherapy is established as a first-line treatment and standard of care for patients with metastatic castration-resistant prostate cancer. However, half of the patients do not respond to treatment and those do respond eventually become refractory. A better understanding of the resistance mechanisms to taxane chemotherapy is both urgent and clinical significant, as taxanes (docetaxel and cabazitaxel) are being used in various clinical settings. Sustained signaling through the androgen receptor (AR) has been established as a hallmark of CRPC. Recently, splicing variants of AR (AR-Vs) that lack the ligand-binding domain (LBD) have been identified. These variants are constitutively active and drive prostate cancer growth in a castration-resistant manner. In taxane-resistant cell lines, we found the expression of a major variant, AR-V7, was upregulated. Furthermore, ectopic expression of two clinically relevant AR-Vs (AR-V7 and ARV567es), but not the full-length AR (AR-FL), reduced the sensitivities to taxanes in LNCaP cells. Treatment with taxanes inhibited the transcriptional activity of AR-FL, but not those of AR-Vs. This could be explained, at least in part, due to the inability of taxanes to block the nuclear translocation of AR-Vs. Through a series of deletion constructs, the microtubule-binding activity was mapped to the LBD of AR. Finally, taxane-induced cytoplasm sequestration of AR-FL was alleviated when AR-Vs were present. These findings provide evidence that constitutively active AR-Vs maintain the AR signaling axis by evading the inhibitory effects of microtubule-targeting agents, suggesting that these AR-Vs play a role in resistance to taxane chemotherapy. PMID:26160840

The Direct Inhibitory Effect of Dutasteride or Finasteride on Androgen Receptor Activity is Cell Line Specific

PubMed Central

Chhipa, Rishi Raj; Halim, Danny; Cheng, Jinrong; Zhang, Huan Yi; Mohler, James L.; Ip, Clement; Wu, Yue

2014-01-01

BACKGROUND Finasteride and dutasteride were developed originally as 5α-reductase inhibitors to block the conversion of testosterone to dihydrotestosterone (DHT). These drugs may possess off-target effects on the androgen receptor (AR) due to their structural similarity to DHT. METHODS A total of 4 human prostate cancer cell models were examined: LNCaP (T877A mutant AR), 22Rv1 (H874Y mutant AR), LAPC4 (wild type AR) and VCaP (wild type AR). Cells were cultured in 10% charcoal-stripped fetal bovine serum, either with or without DHT added to the medium. AR activity was evaluated using the ARE-luciferase assay or the expression of AR regulated genes. RESULTS Dutasteride was more potent than finasteride in interfering with DHT-stimulated AR signaling. Disruption of AR function was accompanied by decreased cell growth. Cells that rely on DHT for protection against death were particularly vulnerable to dutasteride. Different prostate cancer cell models exhibited different sensitivities to dutasteride and finasteride. LNCaP was most sensitive, LAPC4 and VCaP were intermediate, while 22Rv1 was least sensitive. Regardless of the AR genotype, if AR was transfected into drug-sensitive cells, AR was inhibited by drug treatment; and if AR was transfected into drug-resistant cells, AR was not inhibited. CONCLUSIONS The direct inhibitory effect of dutasteride or finasteride on AR signaling is cell line specific. Mutations in the ligand binding domain of AR do not appear to play a significant role in influencing the AR antagonistic effect of these drugs. Subcellular constituent is an important factor in determining the drug effect on AR function. PMID:23813737

High-content screening identifies Src family kinases as potential regulators of AR-V7 expression and androgen-independent cell growth

PubMed Central

Szafran, Adam T.; Stephan, Cliff; Bolt, Michael; Mancini, Maureen G.; Marcelli, Marco; Mancini, Michael A.

2018-01-01

Background AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood. Therefore, we aimed to explore existing classes of small molecules that may regulate AR-V7 expression and intracellular localization and their potential therapeutic role in CRPC. Methods We used AR high-content analysis (AR-HCA) to characterize the effects of a focused library of well-characterized clinical compounds on AR-V7 expression at the single-cell level in PC3 prostate cancer cells stably expressing green fluorescent protein (GFP)-AR-V7 (GFP-AR-V7:PC3). In parallel, an orthogonal AR-HCA screen of a small interfering (si)RNA library targeting 635 protein kinases was performed in GFP-AR-V7:PC3. The effect of the Src-Abl inhibitor PD 180970 was further characterized using cell-proliferation assays, quantitative PCR, and western blot analysis in multiple hormone-sensitive and CRPC cell lines. Results Compounds that tended to target Akt, Abl, and Src family kinases (SFKs) decreased overall AR-V7 expression, nuclear translocation, absolute nuclear level, and/or altered nuclear distribution. We identified 20 protein kinases that, when knocked down, either decreased nuclear GFP-AR-V7 levels or altered AR-V7 nuclear distribution, a set that included the SFKs Src and Fyn. The Src-Abl dual kinase inhibitor PD180970 decreased expression of AR-V7 by greater than 46% and decreased ligand-independent transcription of AR target genes in the 22RV1 human prostate carcinoma cell line. Further, PD180970 inhibited androgen-independent cell proliferation in endogenous–AR-V7–expressing prostate cancer cell lines and also overcame bicalutamide resistance observed in the 22RV1 cell line. Conclusions SFKs, especially Src and Fyn, may be important upstream regulators of AR-V7 expression and represent promising targets in a subset of CRPCs expressing high levels of AR-V7. PMID:27699828

Explicit expressions of self-diffusion coefficient, shear viscosity, and the Stokes-Einstein relation for binary mixtures of Lennard-Jones liquids

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

Ohtori, Norikazu, E-mail: ohtori@chem.sc.niigata-u.ac.jp; Ishii, Yoshiki

Explicit expressions of the self-diffusion coefficient, D{sub i}, and shear viscosity, η{sub sv}, are presented for Lennard-Jones (LJ) binary mixtures in the liquid states along the saturated vapor line. The variables necessary for the expressions were derived from dimensional analysis of the properties: atomic mass, number density, packing fraction, temperature, and the size and energy parameters used in the LJ potential. The unknown dependence of the properties on each variable was determined by molecular dynamics (MD) calculations for an equimolar mixture of Ar and Kr at the temperature of 140 K and density of 1676 kg m{sup −3}. The scalingmore » equations obtained by multiplying all the single-variable dependences can well express D{sub i} and η{sub sv} evaluated by the MD simulation for a whole range of compositions and temperatures without any significant coupling between the variables. The equation for D{sub i} can also explain the dual atomic-mass dependence, i.e., the average-mass and the individual-mass dependence; the latter accounts for the “isotope effect” on D{sub i}. The Stokes-Einstein (SE) relation obtained from these equations is fully consistent with the SE relation for pure LJ liquids and that for infinitely dilute solutions. The main differences from the original SE relation are the presence of dependence on the individual mass and on the individual energy parameter. In addition, the packing-fraction dependence turned out to bridge another gap between the present and original SE relations as well as unifying the SE relation between pure liquids and infinitely dilute solutions.« less

3D Printing Meets Astrophysics: A New Way to Visualize and Communicate Science

NASA Astrophysics Data System (ADS)

Madura, Thomas Ignatius; Steffen, Wolfgang; Clementel, Nicola; Gull, Theodore R.

2015-08-01

3D printing has the potential to improve the astronomy community’s ability to visualize, understand, interpret, and communicate important scientific results. I summarize recent efforts to use 3D printing to understand in detail the 3D structure of a complex astrophysical system, the supermassive binary star Eta Carinae and its surrounding bipolar ‘Homunculus’ nebula. Using mapping observations of molecular hydrogen line emission obtained with the ESO Very Large Telescope, we obtained a full 3D model of the Homunculus, allowing us to 3D print, for the first time, a detailed replica of a nebula (Steffen et al. 2014, MNRAS, 442, 3316). I also present 3D prints of output from supercomputer simulations of the colliding stellar winds in the highly eccentric binary located near the center of the Homunculus (Madura et al. 2015, arXiv:1503.00716). These 3D prints, the first of their kind, reveal previously unknown ‘finger-like’ structures at orbital phases shortly after periastron (when the two stars are closest to each other) that protrude outward from the spiral wind-wind collision region. The results of both efforts have received significant media attention in recent months, including two NASA press releases (http://www.nasa.gov/content/goddard/astronomers-bring-the-third-dimension-to-a-doomed-stars-outburst/ and http://www.nasa.gov/content/goddard/nasa-observatories-take-an-unprecedented-look-into-superstar-eta-carinae/), demonstrating the potential of using 3D printing for astronomy outreach and education. Perhaps more importantly, 3D printing makes it possible to bring the wonders of astronomy to new, often neglected, audiences, i.e. the blind and visually impaired.

The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.

PubMed

Nakata, Daisuke; Nakao, Shoichi; Nakayama, Kazuhide; Araki, Shinsuke; Nakayama, Yusuke; Aparicio, Samuel; Hara, Takahito; Nakanishi, Atsushi

2017-01-29

Mounting evidence suggests that constitutively active androgen receptor (AR) splice variants, typified by AR-V7, are associated with poor prognosis and resistance to androgen deprivation therapy in prostate cancer patients. However, mechanisms governing the generation of AR splice variants are not fully understood. In this study, we aimed to investigate the dynamics of AR splice variant generation using the JDCaP prostate cancer model that expresses AR splice variants under androgen depletion. Microarray analysis of JDCaP xenografts before and after expression of AR splice variants suggested that dysregulation of RNA processing pathways is likely involved in AR splice variant generation. To explore factors contributing to generation of AR-V7 mRNA, we conducted a focused RNA interference screen in AR-V7-positive JDCaP-hr cells using an shRNA library targeting spliceosome-related genes. This screen identified DDX39B as a regulator of AR-V7 mRNA expression. Simultaneous knockdown of DDX39B and its paralog DDX39A drastically and selectively downregulated AR-V7 mRNA expression in multiple AR-V7-positive prostate cancer cell lines. DDX39B was upregulated in relapsed JDCaP xenografts expressing AR splice variants, suggesting its role in expression of AR splice variants. Taken together, our findings offer insight into the mechanisms of AR splice variant generation and identify DDX39 as a potential drug target for the treatment of AR splice variant-positive prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

International consensus statement on allergy and rhinology: allergic rhinitis-executive summary.

PubMed

Wise, Sarah K; Lin, Sandra Y; Toskala, Elina

2018-02-01

The available allergic rhinitis (AR) literature continues to grow. Critical evaluation and understanding of this literature is important to appropriately utilize this knowledge in the care of AR patients. The International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has been produced as a multidisciplinary international effort. This Executive Summary highlights and summarizes the findings of the comprehensive ICAR:AR document. The ICAR:AR document was produced using previously described methodology. Specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. Over 100 individual topics related to AR diagnosis, pathophysiology, epidemiology, disease burden, risk factors, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR were addressed in the comprehensive ICAR:AR document. Herein, the Executive Summary provides a synopsis of these findings. In the ICAR:AR critical review of the literature, several strengths were identified. In addition, significant knowledge gaps exist in the AR literature where current practice is not based on the best quality evidence; these should be seen as opportunities for additional research. The ICAR:AR document evaluates the strengths and weaknesses of the AR literature. This Executive Summary condenses these findings into a short summary. The reader is also encouraged to consult the comprehensive ICAR:AR document for a thorough description of this work. © 2018 ARS-AAOA, LLC.

K/Ar dating of lunar soils. II

NASA Technical Reports Server (NTRS)

Alexander, E. C., Jr.; Bates, A.; Coscio, M. R., Jr.; Dragon, J. C.; Murthy, V. R.; Pepin, R. O.; Venkatesan, T. R.

1976-01-01

An attempt is made to identify those K/Ar techniques which extract the most reliable chronological information from lunar soils and to define the situations in which the best data are obtainable. Results are presented for determinations of the exposure and K/Ar ages of five lunar soil samples, which were performed by applying correlation techniques for a two-component argon structure to stepwise-heated and neutron-irradiated aliquots of grain-sized separates. It is found that ages deduced from Ar-40/surface-correlated Ar-36 vs K-40/surface-correlated Ar-36 and analogous plots of data from grain-sized separates appear to be the best available K/Ar ages of submature to mature lunar soils, that ages deduced from Ar-40 vs Ar-36 and analogous plots which assume a uniform K content can be significantly in error, and that stepwise-heating (Ar-40)-(Ar-39) experiments yield useful information only for simple immature soils where the K-Ar systematics are dominated by a single component.

Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma.

PubMed

Adelaiye-Ogala, Remi; Damayanti, Nur P; Orillion, Ashley R; Arisa, Sreevani; Chintala, Sreenivasulu; Titus, Mark A; Kao, Chinghai; Pili, Roberto

2018-03-23

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer. AR expression has also been reported in other solid tumors, including renal cell carcinoma (RCC), but its biological role here remains unclear. Through integrative analysis of a reverse phase protein array (RPPA), we discovered increased expression of AR in an RCC patient-derived xenograft model of acquired resistance to the receptor tyrosine kinase inhibitor (RTKi) sunitinib. AR expression was increased in RCC cell lines with either acquired or intrinsic sunitinib resistance in vitro. An AR signaling gene array profiler indicated elevated levels of AR target genes in sunitinib-resistant cells. Sunitinib-induced AR transcriptional activity was associated with increased phosphorylation of serine 81 (pS81) on AR. Additionally, AR overexpression resulted in acquired sunitinib resistance, and the AR antagonist enzalutamide-induced AR degradation and attenuated AR downstream activity in sunitinib-resistant cells, also indicated by decreased secretion of human kallikrein 2 (KLK2). Enzalutamide-induced AR degradation was rescued by either proteasome inhibition or by knockdown of the AR ubiquitin ligase speckle-type POZ protein (SPOP). In vivo treatment with enzalutamide and sunitinib demonstrated that this combination efficiently induced tumor regression in an RCC model following acquired sunitinib resistance. Overall, our results suggest the potential role of AR as a target for therapeutic interventions, in combination with RTKi, to overcome drug resistance in RCC. Copyright ©2018, American Association for Cancer Research.

Lack of β2-AR Increases Anxiety-Like Behaviors and Rewarding Properties of Cocaine.

PubMed

Zhu, Huiwen; Liu, Zhiyuan; Zhou, Yiming; Yin, Xuming; Xu, Bo; Ma, Lan; Liu, Xing

2017-01-01

It is well known that β-adrenoceptors (β-ARs) play a critical role in emotional arousal and stressful events, but the specific contributions of the β2-AR subtype to the psychological disorders are largely unknown. To investigate whether β2-AR are involved in anxiety-like behavior and reward to addictive drugs, we conducted a series of behavioral tests on β2-AR knock-out (KO) mice. β2-AR KO mice exhibited increased preference for the dark compartment and closed arm in tests of Light/Dark box and elevated plus maze, indicating that β2-AR deletion elevates level of anxiety or innate fear. β2-AR KO mice also showed decreased immobility in tail suspension test (TST), suggesting that β2-AR deletion inhibits depression-like behavior. Interestingly, β2-AR ablation did not change basal locomotion but significantly increased locomotor activity induced by acute cocaine administration. β2-AR KO mice showed enhanced place preference for cocaine, which could be attenuated by β1-selective AR antagonist betaxolol. Consistently, β2-AR agonist suppressed cocaine-conditioned place preference (CPP). These data indicate that β2-AR deletion enhances acute response and reward to cocaine. Our results suggest that β2-AR regulates anxiety level, depression-like behavior and hedonic properties of cocaine, implicating that β2-AR are the potential targets for the treatment of emotional disorders and cocaine addiction.

Direct Measurement of Recoil Effects on Ar-Ar Standards

NASA Astrophysics Data System (ADS)

Hall, C. M.

2011-12-01

Advances in the precision possible with the Ar-Ar method using new techniques and equipment have led to considerable effort to improve the accuracy of the calibration of interlaboratory standards. However, ultimately the accuracy of the method relies on the measurement of 40Ar*/39ArK ratios on primary standards that have been calibrated with the K-Ar method and, in turn, on secondary standards that are calibrated against primary standards. It is usually assumed that an Ar-Ar total gas age is equivalent to a K-Ar age, but this assumes that there is zero loss of Ar due to recoil. Instead, traditional Ar-Ar total gas ages are in fact Ar retention ages [1] and not, strictly speaking, comparable to K-Ar ages. There have been efforts to estimate the importance of this effect on standards along with prescriptions for minimizing recoil effects [2,3], but these studies have relied on indirect evidence for 39Ar recoil. We report direct measurements of 39Ar recoil for a set of primary and secondary standards using the vacuum encapsulation techniques of [1] and show that significant adjustments to ages assigned to some standards may be needed. The fraction f of 39Ar lost due to recoil for primary standards MMhb-1 hornblende and GA-1550 biotite are 0.00367 and 0.00314 respectively. It is possible to modify the assumed K-Ar ages of these standards so that when using their measured Ar retention 40Ar*/39ArK ratios, one obtains a correct K-Ar age for an unknown, assuming that the unknown sample has zero loss of 39Ar due to recoil. Assuming a primary K-Ar age for MMhb-1 of 520.4 Ma, the modified age would be 522.1 Ma and assuming a primary K-Ar age for GA-1550 of 98.79 Ma [4] yields a modified effective age of 99.09 Ma. Measured f values for secondary standards FCT-3 biotite, FCT-2 sanidine and TCR-2 sanidine are 0.00932, 0.00182 and 0.00039 respectively. Using an R value for FCT-3 biotite relative to MMhb-1 [5], the K-Ar age for this standard would be 27.83 Ma and using R values for FCT and TC sanidines [4] against GA-1550, their K-Ar ages would be 28.06 Ma and 28.41 Ma respectively. For retrospective recalculation purposes, the effective Ar-Ar age of these samples that should yield correct K-Ar ages for unknowns with zero recoil loss would be 28.09 Ma, 28.11 Ma and 28.42 Ma for FCT-3 biotite, FCT-2 sanidine and TCR-2 sanidine respectively. The measured f for FCT-3 appears to explain the R value of it relative to FCT sanidine of 1.0086 found by [8]. From the low T portion of the Ar release spectra of the biotite and amphibole standards, it is clear that the dominant recoil artifact affecting Ar release is the re-implantation mechanism seen in clay samples [1,6,7] and not the loss of 39Ar at the surface of the grain. The geometry of neighboring grains during irradiation and internal defects may predominate in controlling recoil loss. [1] Dong et al., 1995, Science, 267, 355-359. [2] Paine et al., 2006, Geochim.Cosmochim. Acta, 70, 1507-1517. [3] Jourdan et al., 2007, Geochim. Cosmochim. Acta, 71, 2791-2808 [4] Renne et al., 1998, Chem. Geol., 145 117-152. [5] Hall & Farrell, 1995, Earth Planet. Sci. Lett., 133, 327-338. [6] Hall et al., 1997, Earth Planet. Sci. Lett., 148, 287-298. [7] Hall et al., 2000, Econ. Geol., 95, 1739-1752. [8] Di Vincenzo & Roman Skála, 2009, Geochim. Cosmochim. Acta, 73, 493-513.

An alternative hypothesis for high-T 40Ar/39Ar age spectrum discordance in polyphase extraterrestrial materials

NASA Astrophysics Data System (ADS)

Cassata, W. S.; Shuster, D. L.; Renne, P. R.; Weiss, B. P.

2009-12-01

A common feature observed in 40Ar/39Ar age spectra of extraterrestrial (ET) rocks is a conspicuous decrease in the ages of high temperature extractions relative to lower temperature steps and a correlated increase in Ca/K, often succeeded by a monotonic increase in ages. This feature is routinely attributed to recoil-implanted 39Ar from a potassium (K)-rich donor phase into a K-poor receptor phase (e.g., 1,2). While 39Ar recoil redistribution is undoubtedly manifested in many terrestrial and ET 40Ar/39Ar whole-rock age spectra, it cannot easily explain the magnitude of high release temperature 40Ar*/39ArK anomalies observed in Martian meteorites ALH 84001 and Nakhla, as well as other course-grained meteorites and lunar rocks. Depending on the aliquot and sample, 50 - 100% of the pyroxene release spectra in ALH 84001 and Nakhla appear strongly perturbed to lower ages. As the mean recoil distance of 39Ar ~0.1 µm, the recoil hypothesis demands that a high-K phase be ubiquitously distributed amongst sub-micron to micron sized pyroxene crystals to account for the observed pyroxene age spectra. However, in both Nakhla and ALH 84001, pyroxene is often completely isolated from high-K phases and individual grains commonly exceed 100 µm in diameter. 40Ar/39Ar analyses of pyroxene-bearing terrestrial basalts, wherein fine-grained pyroxene and plagioclase are intimately adjoined, show that recoil-implanted 39Ar into pyroxene produces much less precipitous anomalies in 40Ar*/39ArK, as predicted by the recoil lengthscale. An alternative hypothesis is that whole-rock age spectra of ET samples with anomalously low ages at high temperatures may reflect diffusive 40Ar distributions within considerably degassed pyroxene grains. Owing to apparent differences in activation energies between glass and/or plagioclase and pyroxene, 40Ar may diffuse more rapidly from pyroxene under certain high-temperature conditions (i.e., above the temperature at which the extrapolated Ar Arrhenius relationships intersect). Thus, very brief, high-temperature shock-heating events may preferentially degas pyroxene without significantly resetting glass and plagioclase 40Ar/39Ar age spectra. This effect would be enhanced by highly localized shock-heating focused along pyroxene (sub)grain boundaries, as has been inferred in other cases (e.g., 3). The shock and impact origin of this feature may explain its frequent appearance in ET samples, regardless of grain size, as well as the general absence of terrestrial analogs. We will present new 40Ar/39Ar data from Martian meteorites and physical models to distinguish between these competing hypotheses. References Cited: 1. Turner & Cadogan, 1974, Possible effects of 39Ar recoil in 40Ar-39Ar dating. Proc. 5th LPSC, 1601- 1615. 2. Huneke & Smith, 1976, The realities of recoil: 39Ar recoil out of small grains and anomalous age patterns in 40Ar-39Ar dating. Proc. 7th LPSC, 1987-2008. 3. Min et al., 2003, Single grain (U-Th)/He ages from phosphates in Acapulco meteorite and implications for thermal history. EPSL 209, 323-336.

40Ar* loss in experimentally deformed muscovite and biotite with implications for 40Ar/39Ar geochronology of naturally deformed rocks

USGS Publications Warehouse

Cosca, M.; Stunitz, H.; Bourgeix, A.-L.; Lee, J.P.

2011-01-01

The effects of deformation on radiogenic argon (40Ar*) retentivity in mica are described from high pressure experiments performed on rock samples of peraluminous granite containing euhedral muscovite and biotite. Cylindrical cores, ???15mm in length and 6.25mm in diameter, were drilled from granite collected from the South Armorican Massif in northwestern France, loaded into gold capsules, and weld-sealed in the presence of excess water. The samples were deformed at a pressure of 10kb and a temperature of 600??C over a period 29 of hours within a solid medium assembly in a Griggs-type triaxial hydraulic deformation apparatus. Overall shortening in the experiments was approximately 10%. Transmitted light and secondary and backscattered electron imaging of the deformed granite samples reveals evidence of induced defects and for significant physical grain size reduction by kinking, cracking, and grain segmentation of the micas.Infrared (IR) laser (CO2) heating of individual 1.5-2.5mm diameter grains of muscovite and biotite separated from the undeformed granite yield well-defined 40Ar/39Ar plateau ages of 311??2Ma (2??). Identical experiments on single grains separated from the experimentally deformed granite yield results indicating 40Ar* loss of 0-35% in muscovite and 2-3% 40Ar* loss in biotite. Intragrain in situ ultraviolet (UV) laser ablation 40Ar/39Ar ages (??4-10%, 1??) of deformed muscovites range from 309??13 to 264??7Ma, consistent with 0-16% 40Ar* loss relative to the undeformed muscovite. The in situ UV laser ablation 40Ar/39Ar ages of deformed biotite vary from 301 to 217Ma, consistent with up to 32% 40Ar* loss. No spatial correlation is observed between in situ 40Ar/39Ar age and position within individual grains. Using available argon diffusion data for muscovite the observed 40Ar* loss in the experimentally treated muscovite can be utilized to predict average 40Ar* diffusion dimensions. Maximum 40Ar/39Ar ages obtained by UV laser ablation overlap those of the undeformed muscovite, indicating argon loss of <1% and an average effective grain radius for 40Ar* diffusion ???700??m. The UV laser ablation and IR laser incremental 40Ar/39Ar ages indicating 40Ar* loss of 16% and 35%, respectively, are consistent with an average diffusion radius ???100??m. These results support a hypothesis of grain-scale 40Ar* diffusion distances in undeformed mica and a heterogeneous mechanical reduction in the intragrain effective diffusion length scale for 40Ar* in deformed mica. Reduction in the effective diffusion length scale in naturally deformed samples occurs most probably through production of mesoscopic and submicroscopic defects such as, e.g., stacking faults. A network of interconnected defects, continuously forming and annealing during dynamic deformation likely plays an important role in controlling both 40Ar* retention and intragrain distribution in deformed mica. Intragrain 40Ar/39Ar ages, when combined with estimates of diffusion kinetics and distances, may provide a means of establishing thermochronological histories from individual micas. ?? 2011.

Elevated nitrogen metabolism and nitric oxide production are involved in Arabidopsis resistance to acid rain.

PubMed

Qiao, Fang; Zhang, Xi-Min; Liu, Xiang; Chen, Juan; Hu, Wen-Jun; Liu, Ting-Wu; Liu, Ji-Yun; Zhu, Chun-Quan; Ghoto, Kabir; Zhu, Xue-Yi; Zheng, Hai-Lei

2018-06-01

Acid rain (AR) can induce great damages to plants and could be classified into different types according to the different SO 4 2- /NO 3 - ratio. However, the mechanism of plants' responding to different types of AR has not been elucidated clearly. Here, we found that nitric-rich simulated AR (N-SiAR) induced less leaves injury as lower necrosis percentage, better physiological parameters and reduced oxidative damage in the leaves of N-SiAR treated Arabidopsis thaliana compared with sulfate and nitrate mixed (SN-SiAR) or sulfuric-rich (S-SiAR) simulated AR treated ones. Of these three types of SiAR, N-SiAR treated Arabidopsis maintained the highest of nitrogen (N) content, nitrate reductase (NR) and nitrite reductase (NiR) activity as well as N metabolism related genes expression level. Nitric oxide (NO) content showed that N-SiAR treated seedlings had a higher NO level compared to SN-SiAR or S-SiAR treated ones. A series of NO production and elimination related reagents and three NO production-related mutants were used to further confirm the role of NO in regulating acid rain resistance in N-SiAR treated Arabidopsis seedlings. Taken together, we concluded that an elevated N metabolism and enhanced NO production are involved in the tolerance to different types of AR in Arabidopsis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Enzalutamide inhibits androgen receptor-positive bladder cancer cell growth.

PubMed

Kawahara, Takashi; Ide, Hiroki; Kashiwagi, Eiji; El-Shishtawy, Kareem A; Li, Yi; Reis, Leonardo O; Zheng, Yichun; Miyamoto, Hiroshi

2016-10-01

Emerging preclinical evidence suggests that androgen-mediated androgen receptor (AR) signals promote bladder cancer progression. However, little is known about the efficacy of an AR signaling inhibitor, enzalutamide, in the growth of bladder cancer cells. In this study, we compared the effects of enzalutamide and 2 other classic antiandrogens, flutamide and bicalutamide, on androgen-induced bladder cancer cell proliferation, migration, and invasion as well as tumor growth in vivo. Thiazolyl blue cell viability assay, flow cytometry, scratch wound-healing assay, transwell invasion assay, real-time polymerase chain reaction, and reporter gene assay were performed in AR-positive (e.g., UMUC3, TCCSUP, and 647V-AR) and AR-negative (e.g., UMUC3-AR-short hairpin RNA [shRNA], TCCSUP-AR-shRNA, 647V) bladder cancer lines treated with dihydrotestosterone and each AR antagonist. We also used a mouse xenograft model for bladder cancer. Dihydrotestosterone increased bladder cancer cell proliferation, migration, and invasion indicating that endogenous or exogenous AR was functional. Enzalutamide, hydroxyflutamide, and bicalutamide showed similar inhibitory effects, without significant agonist activity, on androgen-mediated cell viability/apoptosis, cell migration, and cell invasion in AR-positive lines. No significant effects of dihydrotestosterone as well as AR antagonists on the growth of AR-negative cells were seen. Correspondingly, in UMUC3 cells, these AR antagonists down-regulated androgen-induced expression of AR, matrix metalloproteinase-2, and interleukin-6. Androgen-enhanced AR-mediated transcriptional activity was also blocked by each AR antagonist exhibiting insignificant agonist activity. In UMUC3 xenograft-bearing mice, oral gavage treatment with each antiandrogen retarded tumor growth, and only enzalutamide demonstrated a statistically significant suppression compared with mock treatment. Our current data support recent observations indicating the involvement of the AR pathway in bladder cancer growth and further suggest that AR antagonists, including enzalutamide, are of therapeutic benefit in AR-positive bladder cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of C3a receptor expression on human leucocytes by the use of novel monoclonal antibodies

PubMed Central

ZWIRNER, J; GÖTZE, O; BEGEMANN, G; KAPP, A; KIRCHHOFF, K; WERFEL, T

1999-01-01

Varying results have been published in the past regarding the reactivity of different leucocyte subpopulations, including neutrophils, monocytes and B lymphocytes, to the anaphylatoxin C3a and its degradation product C3a(desArg). To better characterize the cellular distribution of C3a receptor (C3aR) expression, monoclonal antibodies against two different epitopes on the third extracellular domain of the human C3aR were generated. Quantification of C3aR as compared with C5aR densities was performed on peripheral blood leucocytes by quantitative indirect immunofluorescence. Eosinophils and basophils expressed similar numbers of C3aR and C5aR molecules/cell. On eosinophils 10 700±4500 (mean±SD) C3aR and 14 700±4100 C5aR were found, whereas basophils carried 8100±2100 C3aR and 13 500±3800 C5aR. Monocytes expressed approximately six times more C5aR than C3aR molecules on their surface (6000±2500 C3aR versus 34 100±9300 C5aR molecules) whereas on neutrophils, the expression of C5aR was more than 20 times higher than the expression of C3aR (3100±1000 C3aR versus 63 500±12 200 C5aR). No C3aR expression was detectable on peripheral blood-derived B lymphocytes and on tonsillar B cells before and after stimulation with interleukin-2/Staphylococcus aureus Cowan strain I. Our findings correspond well with the paucity of data on C3a-induced functional activities in monocytes and neutrophils and suggest that eosinophilic and basophilic granulocytes represent the primary effector cells in the peripheral blood which can be stimulated by C3a. PMID:10447728

Paleotemperatures at the lunar surfaces from open system behavior of cosmogenic 38Ar and radiogenic 40Ar

DOE PAGES

Shuster, David L.; Cassata, William S.

2015-02-10

The simultaneous diffusion of both cosmogenic 38Ar and radiogenic 40Ar from solid phases is controlled by the thermal conditions of rocks while residing near planetary surfaces. Combined observations of 38Ar/ 37Ar and 40Ar/ 39Ar ratios during stepwise degassing analyses of neutron-irradiated Apollo samples can distinguish between diffusive loss of Ar due to solar heating of the rocks and that associated with elevated temperatures during or following impact events; the data provide quantitative constraints on the durations and temperatures of each process. From sequentially degassed 38Ar/ 37Ar ratios can be calculated a spectrum of apparent 38Ar exposure ages versus the cumulativemore » release fraction of 37Ar, which is particularly sensitive to conditions at the lunar surface typically over ~106–108 year timescales. Due to variable proportions of K- and Ca-bearing glass, plagioclase and pyroxene, with variability in the grain sizes of these phases, each sample will have distinct sensitivity to, and therefore different resolving power on, past near-surface thermal conditions. Furthermore, we present the underlying assumptions, and the analytical and numerical methods used to quantify the Ar diffusion kinetics in multi-phase whole-rock analyses that provide these constraints.« less

Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

PubMed

Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

2015-12-01

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice.

PubMed

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y; DeMayo, Francesco J; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W

2005-07-05

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, AR(GAL4DBD), which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators.

40Ar/39Ar Ages of Carbonaceous Xenoliths in 2 HED Meteorites

NASA Technical Reports Server (NTRS)

Turrin, B.; Lindsay, F. N.; Park, J.; Herzog, G. F.; Delaney, J. S.; Swisher, C. C., III; Johnson, J.; Zolensky, M.

2016-01-01

The generally young K/Ar and 40Ar/39Ar ages of CM chondrites made us wonder whether carbonaceous xenoliths (CMX) entombed in Howardite–Eucrite–Diogenite (HED) meteorites might retain more radiogenic 40Ar than do ‘free-range’ CM-chondrites. To find out, we selected two HED breccias with carbonaceous inclusions in order to compare the 40Ar/39Ar release patterns and ages of the inclusions with those of nearby HED material. Carbonaceous inclusions (CMXs) in two HED meteorites lost a greater fraction of radiogenic 40Ar than did surrounding host material, but a smaller fraction of it than did free-range CM-chondrites such as Murchison or more heavily altered ones. Importantly, however, the siting of the CMXs in HED matrix did not prevent the 40Ar loss of about 40 percent of the radiogenic 40Ar, even from phases that degas at high laboratory temperatures. We infer that carbonaceous asteroids with perihelia of 1 astronomical unit probably experience losses of at least this size. The usefulness of 40Ar/39Ar dating for samples returned from C-type asteroids may hinge, therefore, on identifying and analyzing separately small quantities of the most retentive phases of carbonaceous chondrites.

Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe.

PubMed

Pratihar, Aditya S; Tripathi, Vishnu P; Yadav, Mukesh P; Dubey, Dharani D

2015-12-01

Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2004, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2004 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727- associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2004 or ars727 remains unaltered by the extended chromosomal context.

High-Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth.

PubMed

Szafran, Adam T; Stephan, Cliff; Bolt, Michael; Mancini, Maureen G; Marcelli, Marco; Mancini, Michael A

2017-01-01

AR-V7 is an androgen receptor (AR) splice variant that lacks the ligand-binding domain and is isolated from prostate cancer cell lines. Increased expression of AR-V7 is associated with the transition from hormone-sensitive prostate cancer to more advanced castration-resistant prostate cancer (CRPC). Due to the loss of the ligand-binding domain, AR-V7 is not responsive to traditional AR-targeted therapies, and the mechanisms that regulate AR-V7 are still incompletely understood. Therefore, we aimed to explore existing classes of small molecules that may regulate AR-V7 expression and intracellular localization and their potential therapeutic role in CRPC. We used AR high-content analysis (AR-HCA) to characterize the effects of a focused library of well-characterized clinical compounds on AR-V7 expression at the single-cell level in PC3 prostate cancer cells stably expressing green fluorescent protein (GFP)-AR-V7 (GFP-AR-V7:PC3). In parallel, an orthogonal AR-HCA screen of a small interfering (si)RNA library targeting 635 protein kinases was performed in GFP-AR-V7:PC3. The effect of the Src-Abl inhibitor PD 180970 was further characterized using cell-proliferation assays, quantitative PCR, and western blot analysis in multiple hormone-sensitive and CRPC cell lines. Compounds that tended to target Akt, Abl, and Src family kinases (SFKs) decreased overall AR-V7 expression, nuclear translocation, absolute nuclear level, and/or altered nuclear distribution. We identified 20 protein kinases that, when knocked down, either decreased nuclear GFP-AR-V7 levels or altered AR-V7 nuclear distribution, a set that included the SFKs Src and Fyn. The Src-Abl dual kinase inhibitor PD180970 decreased expression of AR-V7 by greater than 46% and decreased ligand-independent transcription of AR target genes in the 22RV1 human prostate carcinoma cell line. Further, PD180970 inhibited androgen-independent cell proliferation in endogenous-AR-V7-expressing prostate cancer cell lines and also overcame bicalutamide resistance observed in the 22RV1 cell line. SFKs, especially Src and Fyn, may be important upstream regulators of AR-V7 expression and represent promising targets in a subset of CRPCs expressing high levels of AR-V7. Prostate 77:82-93, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

In situ dating on Mars: A new approach to the K-Ar method utilizing cosmogenic argon

NASA Astrophysics Data System (ADS)

Cassata, William S.

2014-01-01

Cosmogenic argon isotopes are produced in feldspars via nuclear reactions between cosmic rays and Ca and K atoms within the lattice. These cosmogenic isotopes can be used as proxies for K and Ca, much like nuclear reactor-derived 39Ar and 37Ar are used as proxies for K and Ca, respectively, in 40Ar/39Ar geochronology. If Ca and K are uniformly distributed, then the ratio of radiogenic 40Ar (40Ar*) to cosmogenic 38Ar or 36Ar (38Arcos or 36Arcos) is proportional to the difference between the radioisotopic and exposure ages, as well as the K/Ca ratio of the degassing phase. Thus cosmogenic, radiogenic, and trapped Ar isotopes, all of which can be measured remotely and are stable over geologic time, are sufficient to generate an isochron-like diagram from which the isotopic composition of the trapped component may be inferred. Such data also provide a means to assess the extent to which the system has remained closed with respect to 40Ar*, thereby mitigating otherwise unquantifiable uncertainties that complicate the conventional K-Ar dating method.

Ar-40/Ar-39 ages and cosmic ray exposure ages of Apollo 14 samples.

NASA Technical Reports Server (NTRS)

Turner, G.; Huneke, J. C.; Podosek, F. A.; Wasserburg, G. J.

1971-01-01

We have used the Ar-40/Ar-39 dating technique on eight samples of Apollo 14 rocks (14053, 14310), breccia fragments (14321), and soil fragments (14001, 14167). The large basalt fragments give reasonable Ar-40/Ar-39 release patterns and yield well defined crystallization ages of 3.89-3.95 aeons. Correlation of the Ar-40/Ar-39 release patterns with Ar-39/Ar-37 patterns showed that the low temperature fractions with high radiogenic argon loss came from K-rich phases. A highly shocked sample and fragments included in the breccia yield complex release patterns with a low temperature peak. The total argon age of these fragments is 3.95 aeons. Cosmic ray exposure ages on these samples are obtained from the ratio of spallogenic Ar-38 to reactor induced Ar-37 and show a distinct grouping of low exposure ages of 26 m.y. correlated with Cone crater. Other samples have exposure ages of more than 260 m.y. and identify material with a more complex integrated cosmic age exposure history.

The inverse problem of argon diffusion from minerals: Determination of kinetic parameters from stepwise-heating experiments

USGS Publications Warehouse

Brandt, Stephen B.; Rasskazov, S.V.; Brandt, I.S.; Ivanov, A.V.; Kunk, Michael J.

1997-01-01

Results of two routine 40Ar/39Ar stepwise heating experiments on a biotite and a basanite are interpreted in terms of Fick's and Arrhenius' laws. Both patterns represent a saddle-shaped 39Ar release. Argon isotope spectra are suggested to be controlled by the activation energy of diffusion E and the frequency factor D(o). The activation energy of 39Ar is lower than the one of 40Ar. This results in a preferable release of 40Ar relatively to 39Ar at high-temperature steps and an increasing high-temperature wing in the saddle-shaped age spectrum. At low temperatures, considerable losses and irregularities in release of mainly 39Ar are observed, which cause the decreasing low-temperature wing in the 'saddle'. The suggestion of argon losses (mainly of 39Ar) from a loose, 'unstable' zone of the mineral structures becomes justified. The n-irradiation of the samples and the shift of E of 39Ar towards lower values seems to explain the saddle-shaped age-spectra often encountered in 40Ar/39Ar-geochronometry.

40Ar ∗ loss in experimentally deformed muscovite and biotite with implications for 40Ar/ 39Ar geochronology of naturally deformed rocks

NASA Astrophysics Data System (ADS)

Cosca, Michael; Stunitz, Holger; Bourgeix, Anne-Lise; Lee, John P.

2011-12-01

The effects of deformation on radiogenic argon ( 40Ar ∗) retentivity in mica are described from high pressure experiments performed on rock samples of peraluminous granite containing euhedral muscovite and biotite. Cylindrical cores, ˜15 mm in length and 6.25 mm in diameter, were drilled from granite collected from the South Armorican Massif in northwestern France, loaded into gold capsules, and weld-sealed in the presence of excess water. The samples were deformed at a pressure of 10 kb and a temperature of 600 °C over a period 29 of hours within a solid medium assembly in a Griggs-type triaxial hydraulic deformation apparatus. Overall shortening in the experiments was approximately 10%. Transmitted light and secondary and backscattered electron imaging of the deformed granite samples reveals evidence of induced defects and for significant physical grain size reduction by kinking, cracking, and grain segmentation of the micas. Infrared (IR) laser (CO 2) heating of individual 1.5-2.5 mm diameter grains of muscovite and biotite separated from the undeformed granite yield well-defined 40Ar/ 39Ar plateau ages of 311 ± 2 Ma (2σ). Identical experiments on single grains separated from the experimentally deformed granite yield results indicating 40Ar ∗ loss of 0-35% in muscovite and 2-3% 40Ar ∗ loss in biotite. Intragrain in situ ultraviolet (UV) laser ablation 40Ar/ 39Ar ages (±4-10%, 1σ) of deformed muscovites range from 309 ± 13 to 264 ± 7 Ma, consistent with 0-16% 40Ar ∗ loss relative to the undeformed muscovite. The in situ UV laser ablation 40Ar/ 39Ar ages of deformed biotite vary from 301 to 217 Ma, consistent with up to 32% 40Ar ∗ loss. No spatial correlation is observed between in situ40Ar/ 39Ar age and position within individual grains. Using available argon diffusion data for muscovite the observed 40Ar ∗ loss in the experimentally treated muscovite can be utilized to predict average 40Ar ∗ diffusion dimensions. Maximum 40Ar/ 39Ar ages obtained by UV laser ablation overlap those of the undeformed muscovite, indicating argon loss of <1% and an average effective grain radius for 40Ar ∗ diffusion ⩾700 μm. The UV laser ablation and IR laser incremental 40Ar/ 39Ar ages indicating 40Ar ∗ loss of 16% and 35%, respectively, are consistent with an average diffusion radius ≪100 μm. These results support a hypothesis of grain-scale 40Ar ∗ diffusion distances in undeformed mica and a heterogeneous mechanical reduction in the intragrain effective diffusion length scale for 40Ar ∗ in deformed mica. Reduction in the effective diffusion length scale in naturally deformed samples occurs most probably through production of mesoscopic and submicroscopic defects such as, e.g., stacking faults. A network of interconnected defects, continuously forming and annealing during dynamic deformation likely plays an important role in controlling both 40Ar ∗ retention and intragrain distribution in deformed mica. Intragrain 40Ar/ 39Ar ages, when combined with estimates of diffusion kinetics and distances, may provide a means of establishing thermochronological histories from individual micas.

Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

PubMed Central

Hozumi, Hironao; Enomoto, Noriyuki; Kono, Masato; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Sumikawa, Hiromitsu; Johkoh, Takeshi; Nakashima, Ran; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi

2015-01-01

Background In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. Objective We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. Methods Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). Results Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01). Conclusions The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD. PMID:25789468

Impact of Age at Diagnosis and Hypothalamic Involvement on Body Mass Index Z-Score Change in Pediatric Brain Tumor Survivors.

PubMed

Strobel, Katie; Simpson, Pippa; Donohoue, Patricia A; Firat, Selim; Jogal, Sachin

2016-01-01

Obesity risk is increased for pediatric central nervous system tumor survivors. Hypothalamic involvement (HI) by tumor or treatment increases the risk. In healthy children, body mass index (BMI) normally declines until adiposity rebound (AR). We hypothesized that HI and diagnosis before AR would lead to increased BMI at follow-up. A chart review of 114 brain tumor survivors diagnosed between 2001-2011 at the Children's Hospital of Wisconsin extracted tumor location, treatment and BMI z-scores at diagnosis and 2-year follow-up. Children were categorized based on age at diagnosis relative to AR and presence/absence of HI. Children diagnosed pre-AR and post-AR with HI had higher BMI z-scores at 2-year follow-up (pre-AR: 1.6, post-AR: 1.3) than at diagnosis (0.5, 0.6). All groups without HI showed no increase in BMI z-score from diagnosis to 2-year follow-up (pre-AR: 0.7-0.6, during AR: 0.7-0.8, post-AR: 0.7-0.8). The pre-AR and during-AR cohorts with HI had a higher BMI z-score at 2-year follow-up relative to those without HI, while the post-AR group did not. Except for the post-AR group, patients with HI have increased BMI at 2 years after diagnosis compared to those without HI. Diagnosis pre-AR is associated with greater follow-up BMI z-score. © 2016 S. Karger AG, Basel.

Mobile Audience Response Systems at a Continuing Medical Education Conference.

PubMed

Beaumont, Alexandra; Gousseau, Michael; Sommerfeld, Connor; Leitao, Darren; Gooi, Adrian

2017-01-01

Mobile audience response systems (mARS) are electronic systems allowing speakers to ask questions and audience members to respond anonymously and immediately on a screen which enables learners to view their peers' responses as well as their own. mARS encourages increased interaction and active learning. This study aims to examine the perceptions of audience members and speakers towards the implementation of mARS at a national medical conference. mARS was implemented at the CSO Annual Meeting in Winnipeg 2015. Eleven presenters agreed to participate in the mARS trial. Both audience and presenters received instructions. Five-point Likert questions and short answer questions were emailed to all conference attendees and the data was evaluated. Twenty-seven participants responded, 23 audience members and 4 instructors. Overall, responders indicated improved attention, involvement, engagement and recognition of audience's understanding of topics with the use of mARS. mARS was perceived as easy to use, with clear instructions, and the majority of respondents expressed an interest in using mARS in more presentations and in future national medical conferences. Most respondents preferred lectures with mARS over lectures without mARS. Some negative feedback on mARS involved dissatisfaction with how some presenters implemented mARS into the workshops. Overall mARS was perceived positively with the majority of respondents wanting mARS implemented in more national medical conferences. Future studies should look at how mARS can be used as an educational tool to help improve patient outcomes.

Synthesis and reactivity of dimeric Ar'TlTlAr' and trimeric (Ar"T1)3 (Ar', Ar" = bulky terphenyl group) thallium(I) derivatives: Tl(I)-Tl(I) bonding in species ligated by monodentate ligands.

PubMed

Wright, Robert J; Phillips, Andrew D; Hino, Shirley; Power, Philip P

2005-04-06

The synthesis and characterization of three new organothallium(I) compounds are reported. Reaction of (Ar'Li)(2) (Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6-Pr(i)(2))(2)) and Ar"Li (Ar" = C(6)H(3)-2,6-(C(6)H(3)-2,6-Me(2))(2)) with TlCl in Et(2)O afforded (Ar'Tl)(2) (1) and (Ar' 'Tl)(3) (2). The "dithallene" 1 is the heaviest group 13 dimetallene and features a planar, trans-bent structure with Ar'Tl-Tl = 119.74(14) degrees and Tl-Tl = 3.0936(8) A. Compound 2 is the first structurally characterized neutral, three-membered ring species of formula c-(MR)(3) (M = Al-Tl; R = organo group). The Tl(3) ring has Tl-Tl distances in the range ca. 3.21-3.37 A as well as pyramidal Tl geometries. The Tl-Tl bonds in 1 and 2 are outside the range (2.88-2.97 A) of Tl-Tl single bonds in R(2)TlTlR(2) compounds. The weak Tl-Tl bonding in 1 and 2 leads to their dissociation into Ar'Tl and Ar' 'Tl monomers in hexane. The Ar'Tl monomer behaves as a Lewis base and readily forms a 1:1 donor-acceptor complex with B(C(6)F(5))(3) to give Ar'TlB(C(6)F(5))(3), 3. Adduct 3 features an almost linear thallium C(ipso)-Tl-B angle of 174.358(7) degrees and a Tl-B distance of 2.311(2) A, which indicates strong association. Treatment of 1 with a variety of reagents resulted in no reactions. The lower reactivity of 1 is in accord with the reluctance of Tl(I) to undergo oxidation to Tl(III) due to the unreactive character of the 6s(2) electrons.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

PubMed

Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

2017-06-01

Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts.

PubMed

Nash, Claire; Boufaied, Nadia; Mills, Ian G; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

2017-05-05

The androgen receptor (AR) is a transcription factor, and key regulator of prostate development and cancer, which has discrete functions in stromal versus epithelial cells. AR expressed in mesenchyme is necessary and sufficient for prostate development while loss of stromal AR is predictive of prostate cancer progression. Many studies have characterized genome-wide binding of AR in prostate tumour cells but none have used primary mesenchyme or stroma. We applied ChIPseq to identify genomic AR binding sites in primary human fetal prostate fibroblasts and patient derived cancer associated fibroblasts, as well as the WPMY1 cell line overexpressing AR. We identified AR binding sites that were specific to fetal prostate fibroblasts (7534), cancer fibroblasts (629), WPMY1-AR (2561) as well as those common among all (783). Primary fibroblasts had a distinct AR binding profile versus prostate cancer cell lines and tissue, and showed a localisation to gene promoter binding sites 1 kb upstream of the transcriptional start site, as well as non-classical AR binding sequence motifs. We used RNAseq to define transcribed genes associated with AR binding sites and derived cistromes for embryonic and cancer fibroblasts as well as a cistrome common to both. These were compared to several in vivo ChIPseq and transcript expression datasets; which identified subsets of AR targets that were expressed in vivo and regulated by androgens. This analysis enabled us to deconvolute stromal AR targets active in stroma within tumour samples. Taken together, our data suggest that the AR shows significantly different genomic binding site locations in primary prostate fibroblasts compared to that observed in tumour cells. Validation of our AR binding site data with transcript expression in vitro and in vivo suggests that the AR target genes we have identified in primary fibroblasts may contribute to clinically significant and biologically important AR-regulated changes in prostate tissue. Copyright © 2017. Published by Elsevier B.V.

Reconfiguring the AR-TIF2 Protein–Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen

PubMed Central

Fancher, Ashley T.; Hua, Yun; Camarco, Daniel P.; Close, David A.; Strock, Christopher J.

2016-01-01

Abstract The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein–protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins. We reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in U-2 OS cells would behave differently in the CaP cell background. Although we did not observe any significant differences in the compound responses between the assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay would be more amenable to screening, because both the virus and cell culture demands are lower. We implemented a testing paradigm of counter-screens and secondary hit characterization assays that allowed us to identify and deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional activation (AR-TA) through antagonism of AR ligand binding or by non-specifically blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor molecules act distally to AR ligand binding, they have the potential to modulate AR-TA in a cell-specific manner that is distinct from existing anti-androgen drugs, and to overcome the development of resistance to AR antagonism. We anticipate that the application of this testing paradigm to characterize the hits from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed into novel therapeutics for CaP and CRPC. PMID:27606620

Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function.

PubMed

Bao, Jing-Yin; Huang, Yan; Wang, Feng; Peng, Yu-Ping; Qiu, Yi-Hua

2007-01-01

Previous work in our laboratory has shown that alpha-adrenoreceptors (alpha-ARs) and beta-ARs exist on lymphocytes from functional profile, and that the receptors mediate the regulation of lymphocyte function by catecholamines. In the present study, we directly examined the expression of alpha-AR subtypes, alpha(1)-AR and alpha(2)-AR mRNAs, in T lymphocytes and explored the roles of the alpha-AR subtypes and intracellular signal transduction mechanisms linked to the receptors in mediating the modulation of T lymphocyte function. T lymphocytes from mesenteric lymph nodes of rats were purified by using a nylon wool column. Reverse transcription polymerase chain reaction was used to detect the expression of alpha(1)-AR and alpha(2)-AR mRNAs in the freshly isolated T cells and the mitogen concanavalin A (Con A)-activated lymphocytes. Colorimetric methylthiazoletetrazolium assay was employed to measure lymphocyte proliferation induced by Con A. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in the Con A-stimulated lymphocyte culture supernatants were examined by enzyme-linked immunosorbent assay. T cells expressed both alpha(1)-AR and alpha(2)-AR mRNAs. The expression of both alpha(1)-AR and alpha(2)-AR mRNAs was significantly higher in the Con A-activated lymphocytes than in the resting lymphocytes. Phenylephrine, a selective alpha(1)-AR agonist, had no evident effect on lymphocyte proliferation nor on IFN-gamma and IL-4 production induced by Con A. However, the selective alpha(2)-AR agonist clonidine attenuated Con A-induced lymphocyte proliferation as well as IFN-gamma and IL-4 production. The inhibited lymphocyte proliferation and IFN-gamma and IL-4 production by clonidine were blocked by yohimbine, an alpha(2)-AR antagonist. Either phospholipase C inhibitor U-73122 or protein kinase C inhibitor chelerythrine partially prevented the suppressive effect of clonidine on Con A-stimulated lymphocyte proliferation and IL-4 production. T lymphocytes express both alpha(1)-ARs and alpha(2)-ARs, but only the alpha(2)-ARs participate in the suppressive modulation of lymphocyte proliferation and cytokine production in vitro. The inhibitory effect of alpha(2)-AR stimulation on lymphocyte function is partially mediated via the phospholipase C-protein kinase C pathway. (c) 2008 S. Karger AG, Basel.

Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer.

PubMed

Zhu, Yezi; Sharp, Adam; Anderson, Courtney M; Silberstein, John L; Taylor, Maritza; Lu, Changxue; Zhao, Pei; De Marzo, Angelo M; Antonarakis, Emmanuel S; Wang, Mindy; Wu, Xingyong; Luo, Yuling; Su, Nan; Nava Rodrigues, Daniel; Figueiredo, Ines; Welti, Jonathan; Park, Emily; Ma, Xiao-Jun; Coleman, Ilsa; Morrissey, Colm; Plymate, Stephen R; Nelson, Peter S; de Bono, Johann S; Luo, Jun

2018-05-01

Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity. To address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification. We designed a RISH method to visualize single splice junctions in cells and tissue. Using the validated assay for junction-specific detection of the full-length AR (AR-FL) and AR-V7, we generated quantitative data, blinded to clinical data, for 63 prostate tumor biopsies. We evaluated clinical correlates of AR-FL/AR-V7 measurements, including association with prostate-specific antigen progression-free survival (PSA-PFS) and clinical and radiographic progression-free survival (PFS), in a subset of patients starting treatment with abiraterone or enzalutamide following biopsy. Quantitative AR-FL/AR-V7 data were generated from 56 of the 63 (88.9%) biopsy specimens examined, of which 44 were mCRPC biopsies. Positive AR-V7 signals were detected in 34.1% (15/44) mCRPC specimens, all of which also co-expressed AR-FL. The median AR-V7/AR-FL ratio was 11.9% (range 2.7-30.3%). Positive detection of AR-V7 was correlated with indicators of high disease burden at baseline. Among the 25 CRPC biopsies collected before treatment with abiraterone or enzalutamide, positive AR-V7 detection, but not higher AR-FL, was significantly associated with shorter PSA-PFS (hazard ratio 2.789, 95% confidence interval 1.12-6.95; p=0.0081). We report for the first time a RISH method for highly specific and quantifiable detection of splice junctions, allowing further characterization of AR-V7 and its clinical significance. Higher AR-V7 levels detected and quantified using a novel method were associated with poorer response to abiraterone or enzalutamide in prostate cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer.

PubMed

Jones, Dominic; Noble, Martin; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

2017-02-16

Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced. Critically, these effects are reproduced by Aurora A inhibition. We show that Aurora A levels increase in advanced disease and AURKA is an AR-V target gene demonstrating a positive feedback mechanism of androgenic signalling in CRPC. In all, our data suggests that Aurora A plays a pivotal role in regulation of AR-V7 expression and represents a new therapeutic target in CRPC.

Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer

PubMed Central

Jones, Dominic; Noble, Martin; Wedge, Steve R.; Robson, Craig N.; Gaughan, Luke

2017-01-01

Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced. Critically, these effects are reproduced by Aurora A inhibition. We show that Aurora A levels increase in advanced disease and AURKA is an AR-V target gene demonstrating a positive feedback mechanism of androgenic signalling in CRPC. In all, our data suggests that Aurora A plays a pivotal role in regulation of AR-V7 expression and represents a new therapeutic target in CRPC. PMID:28205582

Achievements of the Armenian Astronomy and the Present Activities of the Armenian Astronomical Society

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.

2014-10-01

A report is given on the achievements of the Armenian astronomy during the last years and on the present activities of the Armenian Astronomical Society (ArAS). ArAS membership, ArAS electronic newsletters (ArASNews), ArAS webpage, international collaboration, Armenian Virtual Observatory (ArVO), membership in international organizations, grants, prizes, meetings, summer schools, astronomical Olympiads, other matters related to astronomical education, archaeoastronomy, astronomy outreach and ArAS further projects are discussed.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro.

PubMed

Palethorpe, Helen M; Leach, Damien A; Need, Eleanor F; Drew, Paul A; Smith, Eric

2018-04-10

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo , providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome.

Synergic role of the two ars operons in arsenic tolerance in Pseudomonas putida KT2440.

PubMed

Fernández, Matilde; Udaondo, Zulema; Niqui, José-Luis; Duque, Estrella; Ramos, Juan-Luis

2014-10-01

The chromosome of Pseudomonas putida KT2440 carries two clusters of genes, denoted ars1 and ars2, that are annotated as putative arsenic resistance operons. In this work, we present evidence that both operons encode functional arsenic-response regulatory genes as well as arsenic extrusion systems that confer resistance to both arsenite [As(III)] and arsenate [As(V)]. Transcriptional fusions of P(ars1) and P(ars2) to lacZ revealed that expression of both operons was induced by arsenite and arsenate. We generated single mutants in ars1 and ars2, which showed lower resistance to arsenic than the wild-type strain. A double ars1/ars2 was found to be highly sensitive to arsenic. Minimum inhibitory concentrations (MICs) for single mutants decreased two- to fourfold with respect to the parental strain, while in the double mutant the MIC decreased 128-fold for arsenite and 32-fold for arsenate. Bioinformatic analysis revealed that the ars2 resistance operon is part of the core genome of P. putida, while the ars1 operon appears to only occur in the KT2440 strain, suggesting that ars1 was acquired by horizontal gene transfer. The presence of ars1 in KT2440 may explain why it exhibits higher resistance to arsenic than other P. putida strains, which bear only the ars2 operon.

Ar/Ar Dating Independent of Monitor Standard Ages

NASA Astrophysics Data System (ADS)

Boswell, S.; Hemming, S. R.

2015-12-01

Because the reported age of an analyzed sample is dependent on the age of the co-irradiated monitor standard(s), Ar/Ar dating is a relative dating technique. There is disagreement at the 1% scale in the age of commonly used monitor standards, and there is a great need to improve the inter-laboratory calibrations. Additionally, new approaches and insights are needed to meet the challenge of bringing the Ar/Ar chronometer to the highest possible precision and accuracy. In this spirit, we present a conceptual framework for Ar/Ar dating that does not depend on the age of monitor standards, but only on the K content of a solid standard. The concept is demonstrated by introducing a re-expressed irradiation parameter (JK) that depends on the ratio of 39ArK to 40Ar* rather than the 40Ar*/39ArK ratio. JK is equivalent to the traditional irradiation parameter J and is defined as JK = (39Ar/40K) • (λ/λe). The ultimate precision and accuracy of the method will depend on how precisely and accurately the 39Ar and 40K can be estimated, and will require isotope dilution measurements of both from the same aliquot. We are testing the workability of our technique at the 1% level by measuring weighed and irradiated hornblende and biotite monitor standards using GLO-1 glauconite to define a calibration curve for argon signals versus abundance.

The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions.

PubMed

Abdulrahman, Basant A; Abdelaziz, Dalia; Thapa, Simrika; Lu, Li; Jain, Shubha; Gilch, Sabine; Proniuk, Stefan; Zukiwski, Alexander; Schatzl, Hermann M

2017-12-14

Prion diseases are fatal infectious neurodegenerative disorders that affect both humans and animals. The autocatalytic conversion of the cellular prion protein (PrP C ) into the pathologic isoform PrP Sc is a key feature in prion pathogenesis. AR-12 is an IND-approved derivative of celecoxib that demonstrated preclinical activity against several microbial diseases. Recently, AR-12 has been shown to facilitate clearance of misfolded proteins. The latter proposes AR-12 to be a potential therapeutic agent for neurodegenerative disorders. In this study, we investigated the role of AR-12 and its derivatives in controlling prion infection. We tested AR-12 in prion infected neuronal and non-neuronal cell lines. Immunoblotting and confocal microscopy results showed that AR-12 and its analogue AR-14 reduced PrP Sc levels after only 72 hours of treatment. Furthermore, infected cells were cured of PrP Sc after exposure of AR-12 or AR-14 for only two weeks. We partially attribute the influence of the AR compounds on prion propagation to autophagy stimulation, in line with our previous findings that drug-induced stimulation of autophagy has anti-prion effects in vitro and in vivo. Taken together, this study demonstrates that AR-12 and the AR-14 analogue are potential new therapeutic agents for prion diseases and possibly protein misfolding disorders involving prion-like mechanisms.

Characterization of a novel androgen receptor (AR) coregulator RIPK1 and related chemicals that suppress AR-mediated prostate cancer growth via peptide and chemical screening.

PubMed

Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, Ting-Wei; Chang, Ying-Hsu; Kuo, Yung-Chia; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Lee, Li-Yu; Ma, Wen-Lung; Lin, Chun-Cheng; Wu, Wen-Guey

2017-09-19

Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation. In terms of tissue expression, RIPK1 levels were markedly higher in benign prostate hyperplasia and non-cancerous tissue regions relative to the tumor area. With the aid of computer modeling for screening of chemicals targeting activation function 2 (AF-2) of AR, we identified oxadiazole derivatives as good candidates and subsequently generated a small library of these compounds. A number of candidates could effectively suppress AR transactivation and AR-related functions in vitro and in vivo with tolerable toxicity via inhibiting AR-peptide, AR-coregulator and AR N-C interactions. Combination of these chemicals with antiandrogen had an additive suppressive effect on AR transcriptional activity. Our collective findings may pave the way in creating new strategies for the development and design of anti-AR drugs.

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

PubMed

Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

2018-03-01

Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro

PubMed Central

Palethorpe, Helen M.; Leach, Damien A.; Need, Eleanor F.; Drew, Paul A.; Smith, Eric

2018-01-01

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo, providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome. PMID:29721186

32 CFR Appendix A to Part 584 - Reference

Code of Federal Regulations, 2011 CFR

2011-07-01

... Certain Other Units of the Army. AR 340-18 The Army Functional Files System AR 600-240 Marriage in Oversea...-17 Release of Information and Records from Army Files. (Cited in § 584.1(f)(2).) AR 340-21 The Army... regulation. AR 11-2 Internal Control Systems AR 20-1 Inspector General Activities and Procedures AR 140-1...

32 CFR Appendix A to Part 584 - Reference

Code of Federal Regulations, 2013 CFR

2013-07-01

... Certain Other Units of the Army. AR 340-18 The Army Functional Files System AR 600-240 Marriage in Oversea...-17 Release of Information and Records from Army Files. (Cited in § 584.1(f)(2).) AR 340-21 The Army... regulation. AR 11-2 Internal Control Systems AR 20-1 Inspector General Activities and Procedures AR 140-1...

32 CFR Appendix A to Part 584 - Reference

Code of Federal Regulations, 2012 CFR

2012-07-01

... Certain Other Units of the Army. AR 340-18 The Army Functional Files System AR 600-240 Marriage in Oversea...-17 Release of Information and Records from Army Files. (Cited in § 584.1(f)(2).) AR 340-21 The Army... regulation. AR 11-2 Internal Control Systems AR 20-1 Inspector General Activities and Procedures AR 140-1...

32 CFR Appendix A to Part 584 - Reference

Code of Federal Regulations, 2014 CFR

2014-07-01

... Certain Other Units of the Army. AR 340-18 The Army Functional Files System AR 600-240 Marriage in Oversea...-17 Release of Information and Records from Army Files. (Cited in § 584.1(f)(2).) AR 340-21 The Army... regulation. AR 11-2 Internal Control Systems AR 20-1 Inspector General Activities and Procedures AR 140-1...

Gas mixtures for gas-filled particle detectors

DOEpatents

Christophorou, Loucas G.; McCorkle, Dennis L.; Maxey, David V.; Carter, James G.

1980-01-01

Improved binary and tertiary gas mixtures for gas-filled particle detectors are provided. The components are chosen on the basis of the principle that the first component is one gas or mixture of two gases having a large electron scattering cross section at energies of about 0.5 eV and higher, and the second component is a gas (Ar) having a very small cross section at and below aout 0.5 eV, whereby fast electrons in the gaseous mixture are slowed into the energy range of about 0.5 eV where the cross section for the mixture is small and hence the electron mean free path is large. The reduction in both the cross section and the electron energy results in an increase in the drift velocity of the electrons in the gas mixtures over that for the separate components for a range of E/P (pressure-reduced electron field) values. Several gas mixtures are provided that provide faster response in gas-filled detectors for convenient E/P ranges as compared with conventional gas mixtures.

Improved gas mixtures for gas-filled particle detectors

DOEpatents

Christophorou, L.G.; McCorkle, D.L.; Maxey, D.V.; Carter, J.G.

Improved binary and tertiary gas mixture for gas-filled particle detectors are provided. The components are chosen on the basis of the principle that the first component is one gas or mixture of two gases having a large electron scattering cross section at energies of about 0.5 eV and higher, and the second component is a gas (Ar) having a very small cross section at and below about 0.5 eV; whereby fast electrons in the gaseous mixture are slowed into the energy range of about 0.5 eV where the cross section for the mixture is small and hence the electron mean free path is large. The reduction in both the cross section and the electron energy results in an increase in the drift velocity of the electrons in the gas mixtures over that for the separate components for a range of E/P (pressure-reduced electron field) values. Several gas mixtures are provided that provide faster response in gas-filled detectors for convenient E/P ranges as compared with conventional gas mixtures.

Robust kernel representation with statistical local features for face recognition.

PubMed

Yang, Meng; Zhang, Lei; Shiu, Simon Chi-Keung; Zhang, David

2013-06-01

Factors such as misalignment, pose variation, and occlusion make robust face recognition a difficult problem. It is known that statistical features such as local binary pattern are effective for local feature extraction, whereas the recently proposed sparse or collaborative representation-based classification has shown interesting results in robust face recognition. In this paper, we propose a novel robust kernel representation model with statistical local features (SLF) for robust face recognition. Initially, multipartition max pooling is used to enhance the invariance of SLF to image registration error. Then, a kernel-based representation model is proposed to fully exploit the discrimination information embedded in the SLF, and robust regression is adopted to effectively handle the occlusion in face images. Extensive experiments are conducted on benchmark face databases, including extended Yale B, AR (A. Martinez and R. Benavente), multiple pose, illumination, and expression (multi-PIE), facial recognition technology (FERET), face recognition grand challenge (FRGC), and labeled faces in the wild (LFW), which have different variations of lighting, expression, pose, and occlusions, demonstrating the promising performance of the proposed method.

Ion beam nanopatterning of III-V semiconductors: Consistency of experimental and simulation trends within a chemistry-driven theory

DOE PAGES

El-Atwani, O.; Norris, S. A.; Ludwig, K.; ...

2015-12-16

In this study, several proposed mechanisms and theoretical models exist concerning nanostructure evolution on III-V semiconductors (particularly GaSb) via ion beam irradiation. However, making quantitative contact between experiment on the one hand and model-parameter dependent predictions from different theories on the other is usually difficult. In this study, we take a different approach and provide an experimental investigation with a range of targets (GaSb, GaAs, GaP) and ion species (Ne, Ar, Kr, Xe) to determine new parametric trends regarding nanostructure evolution. Concurrently, atomistic simulations using binary collision approximation over the same ion/target combinations were performed to determine parametric trends onmore » several quantities related to existing model. A comparison of experimental and numerical trends reveals that the two are broadly consistent under the assumption that instabilities are driven by chemical instability based on phase separation. Furthermore, the atomistic simulations and a survey of material thermodynamic properties suggest that a plausible microscopic mechanism for this process is an ion-enhanced mobility associated with energy deposition by collision cascades.« less

INFRARED SPECTROSCOPY OF SYMBIOTIC STARS. XI. ORBITS FOR SOUTHERN S-TYPE SYSTEMS: HEN 3-461, SY MUS, HEN 3-828, AND AR PAV

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

Fekel, Francis C.; Hinkle, Kenneth H.; Joyce, Richard R.

Employing new infrared radial velocities, we have computed spectroscopic orbits of the cool giants in four southern S-type symbiotic systems. The orbits for two of the systems, Hen 3-461 and Hen 3-828, have been determined for the first time, while orbits of the other two, SY Mus and AR Pav, have previously been determined. For the latter two systems, we compare our results with those in the literature. The low mass of the secondary of SY Mus suggests that it has gone through a common envelope phase. Hen 3-461 has an orbital period of 2271 days, one of the longest currently known for S-type symbiotic systems.more » That period is very different from the orbital period proposed previously from its photometric variations. The other three binaries have periods between 600 and 700 day, values that are typical for S-type symbiotic orbits. Basic properties of the M giant components and the distance to each system are determined.« less

Meat quality and rigor mortis development in broiler chickens with gas-induced anoxia and postmortem electrical stimulation.

PubMed

Sams, A R; Dzuik, C S

1999-10-01

This study was conducted to evaluate the combined rigor-accelerating effects of postmortem electrical stimulation (ES) and argon-induced anoxia (Ar) of broiler chickens. One hundred broilers were processed in the following treatments: untreated controls, ES, Ar, or Ar with ES (Ar + ES). Breast fillets were harvested at 1 h postmortem for all treatments or at 1 and 6 h postmortem for the control carcasses. Fillets were sampled for pH and ratio of inosine to adenosine (R-value) and were then individually quick frozen (IQF) or aged on ice (AOI) until 24 h postmortem. Color was measured in the AOI fillets at 24 h postmortem. All fillets were then cooked and evaluated for Allo-Kramer shear value. The Ar treatment accelerated the normal pH decline, whereas the ES and AR + ES treatments yielded even lower pH values at 1 h postmortem. The Ar + ES treatment had a greater R-value than the ES treatment, which was greater than either the Ar or 1-h controls, which, in turn, were not different from each other. The ES treatment had the lowest L* value, and ES, Ar, and Ar + ES produced significantly higher a* values than the 1-h controls. For the IQF fillets, the ES and Ar + ES treatments were not different in shear value but were lower than Ar, which was lower than the 1-h controls. The same was true for the AOI fillets except that the ES and the Ar treatments were not different. These results indicated that although ES and Ar had rigor-accelerating and tenderizing effects, ES seemed to be more effective than Ar; there was little enhancement when Ar was added to the ES treatment and fillets were deboned at 1 h postmortem.

Structural Changes Due to Antagonist Binding in Ligand Binding Pocket of Androgen Receptor Elucidated Through Molecular Dynamics Simulations.

PubMed

Sakkiah, Sugunadevi; Kusko, Rebecca; Pan, Bohu; Guo, Wenjing; Ge, Weigong; Tong, Weida; Hong, Huixiao

2018-01-01

When a small molecule binds to the androgen receptor (AR), a conformational change can occur which impacts subsequent binding of co-regulator proteins and DNA. In order to accurately study this mechanism, the scientific community needs a crystal structure of the Wild type AR (WT-AR) ligand binding domain, bound with antagonist. To address this open need, we leveraged molecular docking and molecular dynamics (MD) simulations to construct a structure of the WT-AR ligand binding domain bound with antagonist bicalutamide. The structure of mutant AR (Mut-AR) bound with this same antagonist informed this study. After molecular docking analysis pinpointed the suitable binding orientation of a ligand in AR, the model was further optimized through 1 μs of MD simulations. Using this approach, three molecular systems were studied: (1) WT-AR bound with agonist R1881, (2) WT-AR bound with antagonist bicalutamide, and (3) Mut-AR bound with bicalutamide. Our structures were very similar to the experimentally determined structures of both WT-AR with R1881 and Mut-AR with bicalutamide, demonstrating the trustworthiness of this approach. In our model, when WT-AR is bound with bicalutamide, Val716/Lys720/Gln733, or Met734/Gln738/Glu897 move and thus disturb the positive and negative charge clumps of the AF2 site. This disruption of the AF2 site is key for understanding the impact of antagonist binding on subsequent co-regulator binding. In conclusion, the antagonist induced structural changes in WT-AR detailed in this study will enable further AR research and will facilitate AR targeting drug discovery.

Allergic rhinitis and associated risk of migraine among children: a nationwide population-based cohort study.

PubMed

Wang, I-Chung; Tsai, Jeng-Dau; Lin, Cheng-Li; Shen, Te-Chun; Li, Tsai-Chung; Wei, Chang-Ching

2016-03-01

Increased frequency of migraine was reported in adults with allergic rhinitis (AR). Although migraine is less common in children than in adults, it can begin in early childhood and persist into adulthood. We conducted this population-based cohort study to investigate the incidence and subsequent risk of migraine in children with AR. From 2000 to 2007, 461,850 children with recently diagnosed AR and 460,718 non-AR controls were included in the study. By the end of 2008, incidences of migraine in both cohorts, the AR to non-AR cohort hazard ratios (HRs), and confidence intervals (CIs) were measured. The incidence of migraine during the study period was 3.2-fold higher in the AR cohort (95% CI, 2.97 to 3.46) than in the non-AR cohort (11.4 vs 3.49 per 10000 person-years). The risk was greater for boys than for girls, and for children aged <6 years. The HR for migraine in children with AR was 1.44 (95% CI, 1.31 to 1.58) for those with ≤2 annual AR-related medical visits, whereas, 14.8 (95% CI, 13.6 to 16.2) for those with >4 visits (p < 0.0001, the trend test). The risk of migraine development in the AR cohort was highest within the first year after AR diagnosis (HR 4.89; 95% CI, 3.98 to 6.00). Children with AR were more likely to have migraine without aura than migraine with aura. Children with AR had a higher incidence and subsequent risk of migraine. Physicians should be more aware of migraine in children with AR who complain of headache. © 2015 ARS-AAOA, LLC.

Coronal Heating and the Magnetic Field in Solar Active Regions

NASA Astrophysics Data System (ADS)

Falconer, D. A.; Tiwari, S. K.; Winebarger, A. R.; Moore, R. L.

2017-12-01

A strong dependence of active-region (AR) coronal heating on the magnetic field is demonstrated by the strong correlation of AR X-ray luminosity with AR total magnetic flux (Fisher et al 1998 ApJ). AR X-ray luminosity is also correlated with AR length of strong-shear neutral line in the photospheric magnetic field (Falconer 1997). These two whole-AR magnetic parameters are also correlated with each other. From 150 ARs observed within 30 heliocentric degrees from disk center by AIA and HMI on SDO, using AR luminosity measured from the hot component of the AIA 94 Å band (Warren et al 2012, ApJ) near the time of each of 3600 measured HMI vector magnetograms of these ARs and a wide selection of whole-AR magnetic parameters from each vector magnetogram after it was deprojected to disk center, we find: (1) The single magnetic parameter having the strongest correlation with AR 94-hot luminosity is the length of strong-field neutral line. (2) The two-parameter combination having the strongest still-stronger correlation with AR 94-hot luminosity is a combination of AR total magnetic flux and AR neutral-line length weighted by the vertical-field gradient across the neutral line. We interpret these results to be consistent with the results of both Fisher et al (1998) and Falconer (1997), and with the correlation of AR coronal loop heating with loop field strength recently found by Tiwari et al (2017, ApJ Letters). Our interpretation is that, in addition to depending strongly on coronal loop field strength, AR coronal heating has a strong secondary positive dependence on the rate of flux cancelation at neutral lines at coronal loop feet. This work was funded by the Living With a Star Science and Heliophysics Guest Investigators programs of NASA's Heliophysics Division.

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice

PubMed Central

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y.; DeMayo, Francesco J.; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W.

2005-01-01

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, ARGAL4DBD, which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators. PMID:15983373

Armenian Astronomical Society (ArAS) activities

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.

2016-09-01

A review on the activities and achievements of Armenian Astronomical Society (ArAS) and Armenian astronomy in general during the last years is given. ArAS membership, ArAS electronic newsletters (ArASNews), ArAS webpage, Annual Meetings, Annual Prize for Young Astronomers (Yervant Terzian Prize) and other awards, international relations, presence in international organizations, local and international summer schools, science camps, astronomical Olympiads and other events, matters related to astronomical education, astronomical heritage, amateur astronomy, astronomy outreach and ArAS further projects are described and discussed.

Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

DTIC Science & Technology

2013-10-01

that disrupt more selective classes of LxxLL motifs: for example, we have compounds that can block AR-PELP1 and AR- hsp27 interaction through the LxxLL...motif as well as compounds that only block AR-PELP1 (and not AR- hsp27 ). We believe that these compounds will be critical for ascertaining the...IP: AR Input PELP1 PELP1 AR AR Hsp27 hsp27 10 Planned structural modifications of D2-derived peptidomimetics by docking

Characterization of the cod (Gadus morhua) steroidogenic acute regulatory protein (StAR) sheds light on StAR gene structure in fish.

PubMed

Goetz, Frederick W; Norberg, Birgitta; McCauley, Linda A R; Iliev, Dimitar B

2004-03-01

The full-length cDNA for the cod (Gadus morhua) StAR was cloned by RT-PCR and library screening using ovarian RNA. From the library screening, 2 size classes of cDNA were obtained; a 1577 bp cDNA (cStAR1) and a 2851 bp cDNA (cStAR2). The cStAR1 cDNA presumably encodes a protein of 286 amino acids. The cStAR2 cDNA was composed of 6 separated sequences that contained all of the coding regions of cStAR1 when added together, but also contained 5 noncoding regions not observed in cStAR1. Polymerase chain reactions of cod genomic DNA produced products slightly larger than cStAR2. The sequence of these products were the same as cStAR2 but revealed one additional noncoding region (intron). Thus, the fish StAR gene contains the same number of exons (7) and introns (6) as observed in mammals, but is approximately half the size of the mammalian gene. Using Northern analysis and RT-PCR, cStAR1 expression was observed only in testes, ovaries and head kidneys. Polymerase chain reaction products were also observed using cDNA from steroidogenic tissues and primers designed to regions specific for cStAR2, indicating that cStAR2 is expressed in tissues and may account for the presence of larger transcripts observed on Northern blots.

Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

PubMed

Shiina, T; Kawasaki, A; Nagao, T; Kurose, H

2000-09-15

The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

Risk factors for allergic rhinitis in Costa Rican children with asthma.

PubMed

Bunyavanich, S; Soto-Quiros, M E; Avila, L; Laskey, D; Senter, J M; Celedón, J C

2010-02-01

Risk factors for allergic rhinitis (AR) in asthmatics are likely distinct from those for AR or asthma alone. We sought to identify clinical and environmental risk factors for AR in children with asthma. We performed a cross-sectional study of 616 Costa Rican children aged 6-14 years with asthma. Candidate risk factors were drawn from questionnaire data, spirometry, methacholine challenge testing, skin testing, and serology. Two outcome measures, skin test reaction (STR)-positive AR and physician-diagnosed AR, were examined by logistic regression. STR-positive AR had high prevalence (80%) in Costa Rican children with asthma, and its independent risk factors were nasal symptoms after exposure to dust or mold, parental history of AR, older age at asthma onset, oral steroid use in the past year, eosinophilia, and positive IgEs to dust mite and cockroach. Physician-diagnosed AR had lower prevalence (27%), and its independent risk factors were nasal symptoms after pollen exposure, STR to tree pollens, a parental history of AR, inhaled steroid and short-acting beta2 agonist use in the past year, household mold/mildew, and fewer older siblings. A physician's diagnosis was only 29.5% sensitive for STR-positive AR. Risk factors for AR in children with asthma depend on the definition of AR. Indoor allergens drive risk for STR-positive AR. Outdoor allergens and home environmental conditions are risk factors for physician-diagnosed AR. We propose that children with asthma in Costa Rica and other Latin American nations undergo limited skin testing or specific IgE measurements to reduce the current under-diagnosis of AR.

Polyclonal antibody against a complement-activating pectin from the roots of Angelica acutiloba.

PubMed

Wang, N L; Kiyohara, H; Matsumoto, T; Otsuka, H; Hirano, M; Yamada, H

1994-10-01

Anti-sera against a complement-activating pectin (AR-2IIb), which was purified from the roots of Angelica acutiloba Kitagawa, were obtained by immunization of rabbits, and a polyclonal anti-AR-2IIb antibody of the IgG class was purified by affinity chromatography on AR-2IIb-immobilized Sepharose and Protein G-Sepharose. Periodate oxidation of AR-2IIb significantly reduced its inhibitory activity on the reactivity of AR-2IIb to anti-AR-2IIb-IgG, but pronase digestion of AR-2IIb did not affect its inhibitory activity. Other pharmacologically active pectins from A. autiloba, Bupleurum falcatum, and Glycyrrhiza uralensis and the complement-activating pectic arabinogalactan from A. autiloba also showed significant inhibitory activities on the reactivity of AR-2IIb to anti-AR-2IIb-IgG, but these inhibitory activities were lower than that of AR-2IIb. Other pectins, polygalacturonic acid, arabinogalactan, galactan, and araban tested had negligible inhibitory activity. Endo-a-(1-->4)-polygalacturonase digestion of AR-2IIb indicated that its "ramified" region (rhamnogalacturonan core possessing neutral oligosaccharide side-chains) contained epitopes for anti-AR-2IIb-IgG, but that 2-keto-3-deoxyoctulosonic acid (KDO)-containing regions and oligogalacturonides obtained from AR-2IIb were not recognized by anti-AR-2IIb-IgG. Although carboxyl-reduction of galacturonic acid in the "ramified" region decreased the inhibitory activity of the "ramified" on its reactivity to anti-AR-2IIb, an acidic tetrasaccharide unit in the rhamnogalacturonan core had negligible inhibitory activity.

Regulation of Androgen Receptor-Mediated Transcription by RPB5 Binding Protein URI/RMP ▿

PubMed Central

Mita, Paolo; Savas, Jeffrey N.; Djouder, Nabil; Yates, John R.; Ha, Susan; Ruoff, Rachel; Schafler, Eric D.; Nwachukwu, Jerome C.; Tanese, Naoko; Cowan, Nicholas J.; Zavadil, Jiri; Garabedian, Michael J.; Logan, Susan K.

2011-01-01

Androgen receptor (AR)-mediated transcription is modulated by interaction with coregulatory proteins. We demonstrate that the unconventional prefoldin RPB5 interactor (URI) is a new regulator of AR transcription and is critical for antagonist (bicalutamide) action. URI is phosphorylated upon androgen treatment, suggesting communication between the URI and AR signaling pathways. Whereas depletion of URI enhances AR-mediated gene transcription, overexpression of URI suppresses AR transcriptional activation and anchorage-independent prostate cancer cell growth. Repression of AR-mediated transcription is achieved, in part, by URI binding and regulation of androgen receptor trapped clone 27 (Art-27), a previously characterized AR corepressor. Consistent with this idea, genome-wide expression profiling in prostate cancer cells upon depletion of URI or Art-27 reveals substantially overlapping patterns of gene expression. Further, depletion of URI increases the expression of the AR target gene NKX-3.1, decreases the recruitment of Art-27, and increases AR occupancy at the NKX-3.1 promoter. While Art-27 can bind AR directly, URI is bound to chromatin prior to hormone-dependent recruitment of AR, suggesting a role for URI in modulating AR recruitment to target genes. PMID:21730289

Instrumentation development for In Situ 40Ar/39Ar planetary geochronology

USGS Publications Warehouse

Morgan, Leah; Munk, Madicken; Davidheiser-Kroll, Brett; Warner, Nicholas H.; Gupta, Sanjeev; Slaybaugh, Rachel; Harkness, Patrick; Mark, Darren

2017-01-01

The chronology of the Solar System, particularly the timing of formation of extra-terrestrial bodies and their features, is an outstanding problem in planetary science. Although various chronological methods for in situ geochronology have been proposed (e.g., Rb-Sr, K-Ar), and even applied (K-Ar), the reliability, accuracy, and applicability of the 40Ar/39Ar method makes it by far the most desirable chronometer for dating extra-terrestrial bodies. The method however relies on the neutron irradiation of samples, and thus a neutron source. Herein, we discuss the challenges and feasibility of deploying a passive neutron source to planetary surfaces for the in situ application of the 40Ar/39Ar chronometer. Requirements in generating and shielding neutrons, as well as analysing samples are described, along with an exploration of limitations such as mass, power and cost. Two potential solutions for the in situ extra-terrestrial deployment of the 40Ar/39Ar method are presented. Although this represents a challenging task, developing the technology to apply the 40Ar/39Ar method on planetary surfaces would represent a major advance towards constraining the timescale of solar system formation and evolution.

The cloud-radiative forcing of the U.S. landfalling atmospheric rivers

NASA Astrophysics Data System (ADS)

Luo, Qianwen

Atmospheric rivers (ARs) are narrow channels in the atmosphere that transport an enormous amount of moisture from the tropics to the higher latitudes. Streaks of highly reflective clouds are observed along with the ARs in satellite imagery. These clouds both influence the moisture transport of ARs, as well as modify the Earth-Atmospheric energy budget through pathways such as cloud-radiative forcing (CRF). This dissertation studies the CRF of the U.S. Landfalling ARs in weather and climate scales. Three crucial questions are addressed. First, how do clouds produced by the ARs modulate the moisture and heat balance of the Earth-Atmospheric system? Even though studies of ARs date back to the 90s, past research has been primarily focused on their hydrological impacts. We addressed this research gap by comparing the dominant types of precipitating clouds and convection of two ARs. Through quantifying their effects on the energy balance in the midlatitudes, we found that when deep convection was the dominant cloud types of an AR, impressive CRF cooling was produced. Second, what are the sufficient climate conditions for the extensive CRF in the continental U.S.? We studied 60 ARs that reached the California coast (the Southwest ARs) and 60 ARs that reached Pacific Northwest during Nov-Mar, 2000-2008. It was found that when these West-Coast ARs were followed by the moisture surge from the Gulf of Mexico (the Gulf-Coast AR), it resulted in apparent statewide CRF. Such condition happened more frequently in the Southwest-AR scenario. Third, how does the subgrid-scale-convection-induced CRF influence the moisture transport of ARs?We ran two WRF ARW simulations for a Southwest-AR that was followed by a Gulf-Coast AR. The only difference between the two simulations was one considered the CRF of subgrid-scale clouds while the other did not. By comparing the two simulations, we found that the subgrid-scale-convection-induced CRF helped prolong the lifespan of clouds in an AR, thus enabling moisture to be transported further downstream. In short, this work helps improve our understanding of CRF of the U.S. landfalling ARs from both weather and climate perspectives. Our results are useful for validating the representation of clouds and radiation processes in weather and climate models, thereby help to improve AR predictions.

Pig StAR: mRNA expression and alternative splicing in testis and Leydig cells, and association analyses with testicular morphology traits.

PubMed

Zhang, Yanghai; Cui, Yang; Zhang, Xuelian; Wang, Yimin; Gao, Jiayang; Yu, Ting; Lv, Xiaoyan; Pan, Chuanying

2018-05-31

Steroidogenic acute regulatory protein (StAR), primarily expressed in Leydig cells (LCs) in the mammalian testes, is essential for testosterone biosynthesis and male fertility. However, no previous reports have explored the expression profiles, alternative splicing and genetic variations of StAR gene in pig. The aim of current study was to explore the expression profiles in different tissues and different types of testicular cells (LCs; spermatogonial stem cells, SSCs; Sertoli cells, SCs), to identify different splice variants and their expression levels, as well as to detect the indel polymorphism in pig StAR gene. Expression analysis results revealed that StAR was widely expressed in all tested tissues and the expression level in testis was significantly higher than that in other tissues (P < 0.01); among different types of testicular cells, the StAR mRNA expression level was significantly higher in LCs than others (P < 0.05). Furthermore, three splice variants, StAR-a, StAR-b and StAR-c, were first found in pig. Further study showed StAR-a was highly expressed in both testis and LCs when compared with other variants (P < 0.01), suggesting StAR-a was the primary variant at StAR gene post-transcription and may facilitate the combination and transportation of cholesterol with StAR. In addition, a 5-bp duplicated deletion (NC_010457.5:g.5524-5528 delACTTG) was verified in the porcine StAR gene, which was closely related to male testicular morphology traits (P < 0.05), and we speculated that the allele "D" of StAR gene might be a positive allele. Briefly, the current findings suggest that StAR and StAR-a play imperative roles in male fertility and the 5-bp indel can be a potential DNA marker for the marker-assisted selection in boar. Copyright © 2018 Elsevier Inc. All rights reserved.

Observed Trends in West Coast Atmospheric River Temperatures

NASA Astrophysics Data System (ADS)

Gonzales, K. R.; Swain, D. L.; Barnes, E. A.; Diffenbaugh, N. S.

2017-12-01

Understanding the changing characteristics of atmospheric rivers (ARs) in a warming climate is critical in light of their importance in generating precipitation and creating the potential for flood and geophysical hazards. Numerous changes to the characteristics of ARs under the influence of a changing climate have been documented or hypothesized; one simple hypothesis is that AR precipitation will occur at increasingly warm temperatures, potentially altering the critical rain/snow balance in snowpack-dependent watersheds and causing precipitation at higher elevations to fall as rain rather than snow. Not only would warmer, primarily rain-producing ARs greatly affect snow accumulation, but they might also increase the intensity of runoff, the potential for flooding, and the occurrence of rain-on-snow events. Since the West Coast of North America relies heavily on ARs as a source of precipitation and snowpack accumulation, these regions may be profoundly affected by changes in AR temperatures and associated impacts. Using a catalog of ARs encompassing 1979-2014 and ERA-Interim reanalysis, we assess whether detectable trends exist in cool season AR temperatures over the Pacific Coast states of California, Oregon, and Washington. We define AR temperature by the mean temperature of the air mass between 1000 hPa and 750 hPa, and compare AR temperature trends to background temperature trends over the same period. We find overall AR warming over this period and particularly robust warming in March ARs coincident with an apparent poleward shift in March AR frequency. Further analysis suggests that warmer ARs have higher rates of warming than cooler ARs. AR temperature trends generally scale with background temperature trends, although some regions exhibit a near one-to-one relationship while others are largely uncorrelated. The observed warming of ARs making landfall on the West Coast may have potentially significant implications for rain vs. snow at higher elevations, the rain/snow balance, and rain-on-snow flood hazards (particularly in March).

Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian species

USGS Publications Warehouse

Boshra, Hani; Wang, Tiehui; Hove-Madsen, Leif; Hansen, John D.; Li, Jun; Matlapudi, Anjun; Secombes, Christopher J.; Tort, Lluis; Sunyer, J. Oriol

2005-01-01

Virtually nothing is known about the structure, function, and evolutionary origins of the C3aR in nonmammalian species. Because C3aR and C5aR are thought to have arisen from the same common ancestor, the recent characterization of a C5aR in teleost fish implied the presence of a C3aR in this animal group. In this study we report the cloning of a trout cDNA encoding a 364-aa molecule (TC3aR) that shows a high degree of sequence homology and a strong phylogenetic relationship with mammalian C3aRs. Northern blotting demonstrated that TC3aR was expressed primarily in blood leukocytes. Flow cytometric analysis and immunofluorescence microscopy showed that Abs raised against TC3aR stained to a high degree all blood B lymphocytes and, to a lesser extent, all granulocytes. More importantly, these Abs inhibited trout C3a-mediated intracellular calcium mobilization in trout leukocytes. A fascinating structural feature of TC3aR is the lack of a significant portion of the second extracellular loop (ECL2). In all C3aR molecules characterized to date, the ECL2 is exceptionally large when compared with the same region of C5aR. However, the exact function of the extra portion of ECL2 is unknown. The lack of this segment in TC3aR suggests that the extra piece of ECL2 was not necessary for the interaction of the ancestral C3aR with its ligand. Our findings represent the first C3aR characterized in nonmammalian species and support the hypothesis that if C3aR and C5aR diverged from a common ancestor, this event occurred before the emergence of teleost fish.

Revised error propagation of 40Ar/39Ar data, including covariances

NASA Astrophysics Data System (ADS)

Vermeesch, Pieter

2015-12-01

The main advantage of the 40Ar/39Ar method over conventional K-Ar dating is that it does not depend on any absolute abundance or concentration measurements, but only uses the relative ratios between five isotopes of the same element -argon- which can be measured with great precision on a noble gas mass spectrometer. The relative abundances of the argon isotopes are subject to a constant sum constraint, which imposes a covariant structure on the data: the relative amount of any of the five isotopes can always be obtained from that of the other four. Thus, the 40Ar/39Ar method is a classic example of a 'compositional data problem'. In addition to the constant sum constraint, covariances are introduced by a host of other processes, including data acquisition, blank correction, detector calibration, mass fractionation, decay correction, interference correction, atmospheric argon correction, interpolation of the irradiation parameter, and age calculation. The myriad of correlated errors arising during the data reduction are best handled by casting the 40Ar/39Ar data reduction protocol in a matrix form. The completely revised workflow presented in this paper is implemented in a new software platform, Ar-Ar_Redux, which takes raw mass spectrometer data as input and generates accurate 40Ar/39Ar ages and their (co-)variances as output. Ar-Ar_Redux accounts for all sources of analytical uncertainty, including those associated with decay constants and the air ratio. Knowing the covariance matrix of the ages removes the need to consider 'internal' and 'external' uncertainties separately when calculating (weighted) mean ages. Ar-Ar_Redux is built on the same principles as its sibling program in the U-Pb community (U-Pb_Redux), thus improving the intercomparability of the two methods with tangible benefits to the accuracy of the geologic time scale. The program can be downloaded free of charge from http://redux.london-geochron.com.

Significance of the cosmogenic argon correction in deciphering the 40Ar/39Ar ages of the Nakhlite (Martian) meteorites

NASA Astrophysics Data System (ADS)

Cohen, B. E.; Cassata, W.; Mark, D. F.; Tomkinson, T.; Lee, M. R.; Smith, C. L.

2015-12-01

All meteorites contain variable amounts of cosmogenic 38Ar and 36Ar produced during extraterrestrial exposure, and in order to calculate reliable 40Ar/39Ar ages this cosmogenic Ar must be removed from the total Ar budget. The amount of cosmogenic Ar has usually been calculated from the step-wise 38Ar/36Ar, minimum 36Ar/37Ar, or average 38Arcosmogenic/37Ar from the irradiated meteorite fragment. However, if Cl is present in the meteorite, then these values will be disturbed by Ar produced during laboratory neutron irradiation of Cl. Chlorine is likely to be a particular issue for the Nakhlite group of Martian meteorites, which can contain over 1000 ppm Cl [1]. An alternative method for the cosmogenic Ar correction uses the meteorite's exposure age as calculated from an un-irradiated fragment and step-wise production rates based on the measured Ca/K [2]. This calculation is independent of the Cl concentration. We applied this correction method to seven Nakhlites, analyzed in duplicate or triplicate. Selected samples were analyzed at both Lawrence Livermore National Laboratory and SUERC to ensure inter-laboratory reproducibility. We find that the cosmogenic argon correction of [2] has a significant influence on the ages calculated for individual steps, particularly for those at lower temperatures (i.e., differences of several tens of million years for some steps). The lower-temperature steps are more influenced by the alternate cosmogenic correction method of [2], as these analyses yielded higher concentrations of Cl-derived 38Ar. As a result, the Nakhlite data corrected using [2] yields step-heating spectra that are flat or nearly so across >70% of the release spectra (in contrast to downward-stepping spectra often reported for Nakhlite samples), allowing for the calculation of precise emplacement ages for these meteorites. [1] Cartwright J. A. et al. (2013) GCA, 105, 255-293. [2] Cassata W. S., and Borg L. E. (2015) 46th LPSC, Abstract #2742.

The immunohistochemical expression and potential prognostic value of HDAC6 and AR in invasive breast cancer.

PubMed

Li, Congying; Cao, Lu; Xu, Cong; Liu, Fang; Xiang, Guomin; Liu, Xiaozhen; Jiao, Jiao; Niu, Yun

2018-05-01

Previous studies have investigated the role of histone deacetylase 6 (HDAC6) in the regulation of androgen receptor (AR) in prostate cancer; however, the role of HDAC6 has not yet been clearly identified in breast cancer. The aim of this study was to examine the expression of HDAC6 and AR, determine the correlation between HDAC6 and AR, and assess the prognostic value of HDAC6 and AR in breast cancer. A total of 228 cases of invasive breast cancer were randomly selected. The expression of HDAC6 and AR was analyzed by immunohistochemistry. χ 2 Tests were performed to determine the association between conventional clinicopathological factors and HDAC6, AR, and HDAC6/AR co-expression. Spearman correlation methods were performed to determine the correlation between HDAC6 and AR, and Kaplan-Meier analyses were performed to determine the prognostic impact of HDAC6, AR and HDAC6/AR co-expression; 58.8% (134/228) patients exhibited high expression of HDAC6. High HDAC6 expression was significantly associated with high histologic grade (G3) (P<.001) and p53 overexpression (P=.002). HDAC6 and AR expression levels were significantly associated (r=0.382, P<.01). In estrogen receptor (ER)-negative samples, high expression of HDAC6 was more common in the AR+ groups (P<.001) and correlated with high histologic grade (G3) (P=.009), as well as higher HER2 (P=.006) and p53 levels (P=.012). Higher expression of AR and HDAC6 and HDAC6/AR co-expression had a worse clinical prognosis. The expression levels of HDAC6 and AR are correlated in breast cancer; moreover, HDAC6 and AR have prognostic value in predicting the overall survival (OS) of ER-negative breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.

PubMed

Magani, Fiorella; Peacock, Stephanie O; Rice, Meghan A; Martinez, Maria J; Greene, Ann M; Magani, Pablo S; Lyles, Rolando; Weitz, Jonathan R; Burnstein, Kerry L

2017-11-01

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells.

PubMed

Limon-Boulez, I; Bouet-Alard, R; Gettys, T W; Lanier, S M; Maltier, J P; Legrand, C

2001-02-01

alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon is associated with changes in alpha(2)-AR subtype expression (midterm alpha(2A/D)-AR > alpha(2B)-AR; term alpha(2B) >or =alpha(2A/D)-AR), without any change in ACII mRNA, suggesting that alpha(2A/D)- and alpha(2B)-AR differentially regulate beta(2)-cAMP production. To address this issue, we have stably expressed the same density of alpha(2A/D)- or alpha(2B)-AR with AC II in DDT1-MF2 cells. Clonidine (partial agonist) increased beta(2)-AR-stimulated cAMP production in alpha(2A/D)-AR-ACII transfectants but inhibited it in alpha(2B)-AR-ACII transfectants. In contrast, epinephrine (full agonist) enhanced beta(2)-stimulated ACII in both alpha(2A)- and alpha(2B)-ACII clonal cell lines. 4-Azidoanilido-[alpha-(32)P]GTP-labeling of activated G proteins indicated that, in alpha(2B)-AR transfectants, clonidine activated only Gi(2), whereas epinephrine, the full agonist, effectively coupled to Gi(2) and Gi(3). Thus, partial and full agonists selectively activate G proteins that lead to drug specific effects on effectors. Moreover, these data indicate that Gi(3) activation is required for potentiation of beta(2)-AR stimulation of AC by alpha(2A/D) and alpha(2B)-AR in DDT1-MF2 cells. This may reflect an issue of the amount of Gbetagamma released upon receptor activation and/or betagamma composition of Gi(3) versus Gi(2).

[The impact of the androgen receptor splice variant AR-V7 on the prognosis and treatment of advanced prostate cancer].

PubMed

Thelen, P; Taubert, H; Duensing, S; Kristiansen, G; Merseburger, A S; Cronauer, M V

2018-01-25

A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer. This review critically outlines recent advances in AR-V7 diagnostics and presents an overview of current AR-V7 targeted therapies. © Georg Thieme Verlag KG Stuttgart · New York.

Enhanced expression of EGFP gene in CHSE-214 cells by an ARS element from mud loach (Misgurnus mizolepis).

PubMed

Kim, Moo-Sang; Lim, Hak-Seob; Ahn, Sang Jung; Jeong, Yong-Kee; Kim, Chul Geun; Lee, Hyung Ho

2007-11-01

The origins of replication are associated with nuclear matrices or are found in close proximity to matrix attachment regions (MARs). In this report, fish MARs were cloned into an autonomously replicating sequence (ARS) cloning vector and were screened for ARS elements in Saccharomyces cerevisiae. Sixteen clones were isolated that were able to grow on the selective plates. In particular, an ARS905 that shows high efficiency among them was selected for this study. Southern hybridization indicated the autonomous replication of the transformation vector containing the ARS905 element. DNA sequences analysis showed that the ARS905 contained two ARS consensus sequences as well as MAR motifs, such as AT tracts, ORI patterns, and ATC tracts. In vitro matrix binding analysis, major matrix binding activity and ARS function coincided in a subfragment of the ARS905. To analyze the effects of ARS905 on expression of a reporter gene, an ARS905(E1158) with ARS activity was inserted into pBaEGFP(+) containing mud loach beta-actin promoter, EGFP as a reporter gene, and SV40 poly(A) signal. The pBaEGFP(+)-ARS905(E1158) was transfected into a fish cell line, CHSE-214. The intensity of EGFP transfected cells was a 7-fold of the control at 11days post-transfection. These results indicate that ARS905 enhances the expression of the EGFP gene and that it should be as a component of expression vectors in further fish biotechnological studies.

The androgen receptor malignancy shift in prostate cancer.

PubMed

Copeland, Ben T; Pal, Sumanta K; Bolton, Eric C; Jones, Jeremy O

2018-05-01

Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications. In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells. Reinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer. © 2018 Wiley Periodicals, Inc.

Novel galeterone analogs act independently of AR and AR-V7 for the activation of the unfolded protein response and induction of apoptosis in the CWR22Rv1 prostate cancer cell model.

PubMed

McCarty, David J; Huang, Weiliang; Kane, Maureen A; Purushottamachar, Puranik; Gediya, Lalji K; Njar, Vincent C O

2017-10-24

The androgen receptor (AR) has long been the primary target for the treatment of prostate cancer (PC). Despite continuous efforts to block AR activity through ligand depletion, AR antagonism, AR depletion and combinations thereof, advanced PC tumors remain resilient. Herein, we evaluate two galeterone analogs, VNPT-178 and VNLG-74A, in PC cell models of diverse androgen and AR dependence attempting to delineate their mechanisms of action and potential clinical utility. Employing basic biochemical techniques, we determined that both analogs have improved antiproliferative and anti-AR activities compared to FDA-approved abiraterone and enzalutamide. However, induction of apoptosis in these models is independent of the AR and its truncated variant, AR-V7, and instead likely results from sustained endoplasmic reticulum stress and deregulated calcium homeostasis. Using in silico molecular docking, we predict VNPT-178 and VNLG-74A bind the ATPase domain of BiP/Grp78 and Hsp70-1A with greater affinity than the AR. Disruption of 70 kDa heat shock protein function may be the underlying mechanism of action for these galeterone analogs. Therefore, despite simultaneously antagonizing AR activity, AR and/or AR-V7 expression alone may inadequately predict a patient's response to treatment with VNPT-178 or VNLG-74A. Future studies evaluating the context-specific limitations of these compounds may provide clarity for their clinical application.

Cell cycle-coupled expansion of AR activity promotes cancer progression.

PubMed

McNair, C; Urbanucci, A; Comstock, C E S; Augello, M A; Goodwin, J F; Launchbury, R; Zhao, S G; Schiewer, M J; Ertel, A; Karnes, J; Davicioni, E; Wang, L; Wang, Q; Mills, I G; Feng, F Y; Li, W; Carroll, J S; Knudsen, K E

2017-03-23

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

High-Content Positional Biosensor Screening Assay for Compounds to Prevent or Disrupt Androgen Receptor and Transcriptional Intermediary Factor 2 Protein–Protein Interactions

PubMed Central

Hua, Yun; Shun, Tong Ying; Strock, Christopher J.

2014-01-01

Abstract The androgen receptor–transcriptional intermediary factor 2 (AR-TIF2) positional protein–protein interaction (PPI) biosensor assay described herein combines physiologically relevant cell-based assays with the specificity of binding assays by incorporating structural information of AR and TIF2 functional domains along with intracellular targeting sequences and fluorescent reporters. Expression of the AR-red fluorescent protein (RFP) “prey” and TIF2-green fluorescent protein (GFP) “bait” components of the biosensor was directed by recombinant adenovirus constructs that expressed the ligand binding and activation function 2 surface domains of AR fused to RFP with nuclear localization and nuclear export sequences, and three α-helical LXXLL motifs from TIF2 fused to GFP and an HIV Rev nucleolar targeting sequence. In unstimulated cells, AR-RFP was localized predominantly to the cytoplasm and TIF2-GFP was localized to nucleoli. Dihydrotestosterone (DHT) treatment induced AR-RFP translocation into the nucleus where the PPIs between AR and TIF2 resulted in the colocalization of both biosensors within the nucleolus. We adapted the translocation enhanced image analysis module to quantify the colocalization of the AR-RFP and TIF2-GFP biosensors in images acquired on the ImageXpress platform. DHT induced a concentration-dependent AR-TIF2 colocalization and produced a characteristic condensed punctate AR-RFP PPI nucleolar distribution pattern. The heat-shock protein 90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and antiandrogens flutamide and bicalutamide inhibited DHT-induced AR-TIF2 PPI formation with 50% inhibition concentrations (IC50s) of 88.5±12.5 nM, 7.6±2.4 μM, and 1.6±0.4 μM, respectively. Images of the AR-RFP distribution phenotype allowed us to distinguish between 17-AAG and flutamide, which prevented AR translocation, and bicalutamide, which blocked AR-TIF2 PPIs. We screened the Library of Pharmacologically Active Compounds (LOPAC) set for compounds that inhibited AR-TIF2 PPI formation or disrupted preexisting complexes. Eleven modulators of steroid family nuclear receptors (NRs) and 6 non-NR ligands inhibited AR-TIF2 PPI formation, and 10 disrupted preexisting complexes. The hits appear to be either AR antagonists or nonspecific inhibitors of NR activation and trafficking. Given that the LOPAC set represents such a small and restricted biological and chemical diversity, it is anticipated that screening a much larger and more diverse compound library will be required to find AR-TIF2 PPI inhibitors/disruptors. The AR-TIF2 protein–protein interaction biosensor (PPIB) approach offers significant promise for identifying molecules with potential to modulate AR transcriptional activity in a cell-specific manner that is distinct from the existing antiandrogen drugs that target AR binding or production. Small molecules that disrupt AR signaling at the level of AR-TIF2 PPIs may also overcome the development of resistance and progression to castration-resistant prostate cancer. PMID:25181412

Evidence for shock heating and constraints on Martian surface temperatures revealed by 40Ar/ 39Ar thermochronometry of Martian meteorites

NASA Astrophysics Data System (ADS)

Cassata, William S.; Shuster, David L.; Renne, Paul R.; Weiss, Benjamin P.

2010-12-01

The thermal histories of Martian meteorite are important for the interpretation of petrologic, geochemical, geochronological, and paleomagnetic constraints that they provide on the evolution of Mars. In this paper, we quantify 40Ar/ 39Ar ages and Ar diffusion kinetics of Martian meteorites Allan Hills (ALH) 84001, Nakhla, and Miller Range (MIL) 03346. We constrain the thermal history of each meteorite and discuss the resulting implications for their petrology, paleomagnetism, and geochronology. Maskelynite in ALH 84001 yields a 40Ar/ 39Ar isochron age of 4163 ± 35 Ma, which is indistinguishable from recent Pb-Pb ( Bouvier et al., 2009a) and Lu-Hf ages ( Lapen et al., 2010). The high precision of this result arises from clear resolution of a reproducible trapped 40Ar/ 36Ar component in maskelynite in ALH 84001 ( 40Ar/ 36Ar = 632 ± 90). The maskelynite 40Ar/ 39Ar age predates the Late Heavy Bombardment and likely represents the time at which the original natural remanent magnetization (NRM) component observed in ALH 84001 was acquired. Nakhla and MIL 03346 yield 40Ar/ 39Ar isochron ages of 1332 ± 24 and 1339 ± 8 Ma, respectively, which we interpret to date crystallization. Multi-phase, multi-domain diffusion models constrained by the observed Ar diffusion kinetics and 40Ar/ 39Ar age spectra suggest that localized regions within both ALH 84001 and Nakhla were intensely heated for brief durations during shock events at 1158 ± 110 and 913 ± 9 Ma, respectively. These ages may date the marginal melting of pyroxene in each rock, mobilization of carbonates and maskelynite in ALH 84001, and NRM overprints observed in ALH 84001. The inferred peak temperatures of the shock heating events (>1400 °C) are sufficient to mobilize Ar, Sr, and Pb in constituent minerals, which may explain some of the dispersion observed in 40Ar/ 39Ar, Rb-Sr, and U-Th-Pb data toward ages younger than ˜4.1 Ga. The data also place conservative upper bounds on the long-duration residence temperatures of the ALH 84001 and Nakhla protolith to be 22-∞+8 °C and 81-∞+9 °C over the last ˜4.16 Ga and ˜1.35 Ga, respectively. MIL 03346 has apparently not experienced significant shock-heating since it crystallized, consistent with the fact that various chronometers yield concordant ages.

AR-v7 protein expression is regulated by protein kinase and phosphatase

PubMed Central

Li, Yinan; Xie, Ning; Gleave, Martin E.; Rennie, Paul S.; Dong, Xuesen

2015-01-01

Failure of androgen-targeted therapy and progression of castration-resistant prostate cancer (CRPC) are often attributed to sustained expression of the androgen receptor (AR) and its major splice variant, AR-v7. Although the new generation of anti-androgens such as enzalutamide effectively inhibits AR activity, accumulating pre-clinical and clinical evidence indicates that AR-v7 remains constitutively active in driving CRPC progression. However, molecular mechanisms which control AR-v7 protein expression remain unclear. We apply multiple prostate cancer cell models to demonstrate that enzalutamide induces differential activation of protein phosphatase-1 (PP-1) and Akt kinase depending on the gene context of cancer cells. The balance between PP-1 and Akt activation governs AR phosphorylation status and activation of the Mdm2 ubiquitin ligase. Mdm2 recognizes phosphorylated serine 213 of AR-v7, and induces AR-v7 ubiquitination and protein degradation. These findings highlight the decisive roles of PP-1 and Akt for AR-v7 protein expression and activities when AR is functionally blocked. PMID:26378044

Early Thermal History of Eucrites by Ar-39-Ar-40

NASA Technical Reports Server (NTRS)

Bogard, D. D.; Garrison, D. H.

2001-01-01

Ar-39-Ar-40 ages for Piplia Kalan (3.58 +/- 0.02 Ga) and two other eucrites indicate later impact resetting. Older Ar-39-Ar-40 ages exist for the Moama cumulate eucrite (4.42 +/- 0.01 Ga) and the PCA82502 (4.506 +/- 0.009 Ga) and PCA91007 non-brecciated eucrites. Additional information is contained in the original extended abstract.

Growth Inhibition by Testosterone in an Androgen Receptor Splice Variant-Driven Prostate Cancer Model.

PubMed

Nakata, Daisuke; Nakayama, Kazuhide; Masaki, Tsuneo; Tanaka, Akira; Kusaka, Masami; Watanabe, Tatsuya

2016-12-01

Castration resistance creates a significant problem in the treatment of prostate cancer. Constitutively active splice variants of androgen receptor (AR) have emerged as drivers for resistance to androgen deprivation therapy, including the next-generation androgen-AR axis inhibitors abiraterone and enzalutamide. In this study, we describe the characteristics of a novel castration-resistant prostate cancer (CRPC) model, designated JDCaP-hr (hormone refractory). JDCaP-hr was established from an androgen-dependent JDCaP xenograft model after surgical castration. The expression of AR and its splice variants in JDCaP-hr was evaluated by immunoblotting and quantitative reverse transcription-polymerase chain reaction. The effects of AR antagonists and testosterone on JDCaP-hr were evaluated in vivo and in vitro. The roles of full-length AR (AR-FL) and AR-V7 in JDCaP-hr cell growth were evaluated using RNA interference. JDCaP-hr acquired a C-terminally truncated AR protein during progression from the parental JDCaP. The expression of AR-FL and AR-V7 mRNA was upregulated by 10-fold in JDCaP-hr compared with that in JDCaP, indicating that the JDCaP and JDCaP-hr models simulate castration resistance with some clinical features, such as overexpression of AR and its splice variants. The AR antagonist bicalutamide did not affect JDCaP-hr xenograft growth, and importantly, testosterone induced tumor regression. In vitro analysis demonstrated that androgen-independent prostate-specific antigen secretion and cell proliferation of JDCaP-hr were predominantly mediated by AR-V7. JDCaP-hr cell growth displayed a bell-shaped dependence on testosterone, and it was suppressed by physiological concentrations of testosterone. Testosterone induced rapid downregulation of both AR-FL and AR-V7 expression at physiological concentrations and suppressed expression of the AR target gene KLK3. Our findings support the clinical value of testosterone therapy, including bipolar androgen therapy, in the treatment of AR-overexpressed CRPC driven by AR splice variants that are not clinically actionable at present. Prostate 76:1536-1545, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Atmospheric River Development and Effects on Southern California

NASA Astrophysics Data System (ADS)

Harris, S. M.; Carvalho, L. V.

2014-12-01

Throughout most of southern California (SCA) annual precipitation totals occur from relatively few storms per season. Any changes to storm frequency or intensity may dramatically impact the region, as its landscapes are prone to various rainfall-induced hazards including landslides and floods. These hazards become more frequent following drought or fire events, conditions also reliant on precipitation and common in SCA. Rainfall forecasts are especially difficult to determine as regional precipitation is affected by numerous phenomena. On synoptic timescales, atmospheric rivers (ARs) are one such phenomenon known to impact SCA rainfall. ARs are channels of high water vapor content found within the lower atmosphere that transport moisture towards midlatitudes. In areas with varying topography, ARs often produce high-intensity precipitation due to orographic forcing. Although much insight has been gained in understanding AR climatology affecting North America's western coast, the spatiotemporal characteristics and atmospheric forcings driving ARs to SCA need to be further addressed. The goal of this work is to understand the characteristics of ARs that impact SCA and to distinguish them from ARs that impact northern latitudes. We investigate AR characteristics as well as atmospheric features prior to plume initiation for ARs impacting different landfall regions along North America's western coast between 1998-2008. Dates of AR events are organized according to landfall region using total precipitable water (TPW) fields from the National Oceanic and Atmospheric Administration's Climate Forecast System Reanalysis (CFSR). Additional CFSR fields are used to create anomaly composites of moist static energy, geopotential height, as well as upper-level zonal and low-level meridional winds for each landfall region on the day of and prior to AR occurrence. ARs that impact SCA display different TPW plume characteristics as well as wave train patterns throughout the AR lifecycle (prior to plume initiation-AR landfall) compared to ARs that landfall further north. This suggests that ARs impacting SCA differ in initiation mechanisms as well as structural qualities from other ARs. Information from these analyses will assist in creating and validating an automatic tool for identifying AR occurrences.

Functional Characterization of Paralogous Gonadotropin-Releasing Hormone-Type and Corazonin-Type Neuropeptides in an Echinoderm

PubMed Central

Tian, Shi; Egertová, Michaela; Elphick, Maurice R.

2017-01-01

Homologs of the vertebrate neuropeptide gonadotropin-releasing hormone (GnRH) have been identified in invertebrates, including the insect neuropeptide corazonin (CRZ). Recently, we reported the discovery of GnRH-type and CRZ-type signaling systems in an echinoderm, the starfish Asterias rubens, demonstrating that the evolutionary origin of paralogous GnRH-type and CRZ-type neuropeptides can be traced back to the common ancestor of protostomes and deuterostomes. Here, we have investigated the physiological roles of the GnRH-type (ArGnRH) and the CRZ-type (ArCRZ) neuropeptides in A. rubens, using mRNA in situ hybridization, immunohistochemistry and in vitro pharmacology. ArGnRH precursor (ArGnRHP)-expressing cells and ArGnRH-immunoreactive cells and/or processes are present in the radial nerve cords, circumoral nerve ring, digestive system (e.g., cardiac stomach and pyloric stomach), body wall-associated muscle (apical muscle), and appendages (tube feet, terminal tentacle). The general distribution of ArCRZ precursor (ArCRZP)-expressing cells is similar to that of ArGnRHP, but with specific local differences. For example, cells expressing ArGnRHP are present in both the ectoneural and hyponeural regions of the radial nerve cords and circumoral nerve ring, whereas cells expressing ArCRZP were only observed in the ectoneural region. In vitro pharmacological experiments revealed that both ArGnRH and ArCRZ cause contraction of cardiac stomach, apical muscle, and tube foot preparations. However, ArGnRH was more potent/effective than ArCRZ as a contractant of the cardiac stomach, whereas ArCRZ was more potent/effective than ArGnRH as a contractant of the apical muscle. These findings demonstrate that both ArGnRH and ArCRZ are myoexcitatory neuropeptides in starfish, but differences in their expression patterns and pharmacological activities are indicative of distinct physiological roles. This is the first study to investigate the physiological roles of both GnRH-type and CRZ-type neuropeptides in a deuterostome, providing new insights into the evolution and comparative physiology of these paralogous neuropeptide signaling systems in the Bilateria. PMID:29033898

Androgen receptor is overexpressed in boys with severe hypospadias, and ZEB1 regulates androgen receptor expression in human foreskin cells

PubMed Central

Qiao, Liang; Tasian, Gregory E.; Zhang, Haiyang; Cao, Mei; Ferretti, Max; Cunha, Gerald R.; Baskin, Laurence S.

2012-01-01

INTRODUCTION ZEB1 is overexpressed in patients with severe hypospadias. We examined the interaction between ZeB1 and the androgen receptor (AR) in vitro and the expression of AR in boys with hypospadias. RESULTS ZEB1 and AR colocalize to the nucleus. Estrogen upregulated ZEB1 and AR expression. Chromatin immunoprecipitation (ChIP) demonstrated that ZEB1 binds to an E-box sequence in the AR gene promoter. AR expression is higher in subjects with severe hypospadias than those with mild hypospadias and control subjects (P < 0.05). ZEB1 physically interacts with AR in human foreskin cells. DISCUSSION AR is overexpressed in patients with severe hypospadias. Environmental estrogenic compounds may increase the risk of hypospadias by facilitating the interaction between ZEB1 and AR. METHODS Hs68 cells, a fibroblast cell line derived from neonatal human foreskin, were exposed to 0, 10, and 100 nmol/l of estrogen, after which the cellular localization of ZEB1 and AR was assessed using immunocytochemistry. To determine if ZEB1 interacted with the AR gene, ChIP was performed using ZEB1 antibody and polymerase chain reaction (PCR) for AR. Second, AR expression was quantified using real-time PcR and western blot in normal subjects (n = 32), and subjects with mild (n = 16) and severe hypospadia (n = 16). PMID:22391641

Precise K-Ar, 40Ar/39Ar, Rb-Sr and U/Pb mineral ages from the 27.5 Ma fish canyon tuff reference standard

USGS Publications Warehouse

Lanphere, M.A.; Baadsgaard, H.

2001-01-01

The accuracy of ages measured using the 40Ar/39Ar technique is affected by uncertainties in the age of radiation fluence-monitor minerals. At present, there is lack of agreement about the ages of certain minerals used as fluence monitors. The accuracy of the age of a standard may be improved if the age can be measured using different decay schemes. This has been done by measuring ages on minerals from the Oligocene Fish Canyon Tuff (FCT) using the K-Ar, 40Ar/39Ar. Rb-Sr and U/Pb methods. K-Ar and 40Ar/39Ar total fusion ages of sanidine, biotite and hornblende yielded a mean age of 27.57 ?? 0.36 Ma. The weighted mean 40Ar/39Ar plateau age of sanidine and biotite is 27.57 ?? 0.18 Ma. A biotite-feldspar Rb-Sr isochron yielded an age of 27.44 ?? 0.16 Ma. The U-Pb data for zircon are complex because of the presence of Precambrian zircons and inheritance of radiogenic Pb. Zircons with 207Pb/235U < 0.4 yielded a discordia line with a lower concordia intercept of 27.52 ?? 0.09 Ma. Evaluation of the combined data suggests that the best age for FCT is 27.51 Ma. Published by Elsevier Science B.V.

ArsR arsenic-resistance regulatory protein from Cupriavidus metallidurans CH34

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

Zhang, Y.; van der Lelie, D.; Monchy, S.

The Cupriavidus metallidurans CH34 arsR gene, which is part of the arsRIC{sub 2}BC{sub 1}HP operon, and its putative arsenic-resistance regulatory protein were identified and characterized. The arsenic-induced transcriptome of C. metallidurans CH34 showed that the genes most upregulated in the presence of arsenate were all located within the ars operon, with none of the other numerous heavy metal resistance systems present in CH34 being induced. A transcriptional fusion between the luxCDABE operon and the arsR promoter/operator (P/O) region was used to confirm the in vivo induction of the ars operon by arsenite and arsenate. The arsR gene was cloned intomore » expression vectors allowing for the overexpression of the ArsR protein as either his-tagged or untagged protein. The ability of the purified ArsR proteins to bind to the ars P/O region was analyzed in vitro by gel mobility shift assays. ArsR showed an affinity almost exclusively to its own ars P/O region. Dissociation of ArsR and its P/O region was metal dependent, and based on decreasing degrees of dissociation three groups of heavy metals could be distinguished: As(III), Bi(III), Co(II), Cu(II), Ni(II); Cd(II); Pb(II) and Zn(II), while no dissociation was observed in the presence of As(V).« less

Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation.

PubMed

Gaughan, Luke; Logan, Ian R; Neal, David E; Robson, Craig N

2005-01-01

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors and plays a critical role in regulating the expression of genes involved in androgen-dependent and -independent tumour formation. Regulation of the AR is achieved by alternate binding of either histone acetyltransferase (HAT)-containing co-activator proteins, or histone deacetylase 1 (HDAC1). Factors that control AR stability may also constitute an important regulatory mechanism, a notion that has been confirmed with the finding that the AR is a direct target for Mdm2-mediated ubiquitylation and proteolysis. Using chromatin immunoprecipitation (ChIP) and re-ChIP analyses, we show that Mdm2 associates with AR and HDAC1 at the active androgen-responsive PSA promoter in LNCaP prostate cancer cells. Furthermore, we demonstrate that Mdm2-mediated modification of AR and HDAC1 catalyses protein destabilization and attenuates AR sactivity, suggesting that ubiquitylation of the AR and HDAC1 may constitute an additional mechanism for regulating AR function. We also show that HDAC1 and Mdm2 function co-operatively to reduce AR-mediated transcription that is attenuated by the HAT activity of the AR co-activator Tip60, suggesting interplay between acetylation status and receptor ubiquitylation in AR regulation. In all, our data indicates a novel role for Mdm2 in regulating components of the AR transcriptosome.

Cross Sections of the 36Ar(d,α)34mCl, 40Ar(d,α)38Cl and 40Ar(d,p)41Ar Nuclear Reactions below 8.4 MeV

PubMed Central

Engle, J W; Severin, G W; Barnhart, T E; Knutson, L D; Nickles, R J

2011-01-01

We have measured the cross section for production of the medically interesting isotope 34mCl, along with 38Cl and 41Ar, using deuteron bombardments of 36Ar and 40Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas. PMID:22041299

Astronomical calibration of 40Ar/39Ar reference minerals using high-precision, multi-collector (ARGUSVI) mass spectrometry

NASA Astrophysics Data System (ADS)

Phillips, D.; Matchan, E. L.; Honda, M.; Kuiper, K. F.

2017-01-01

The new generation of multi-collector mass spectrometers (e.g. ARGUSVI) permit ultra-high precision (<0.1%) 40Ar/39Ar geochronology of rocks and minerals. At the same time, the 40Ar/39Ar method is limited by relatively large uncertainties (>1%) in 40K decay constants and the ages of natural reference minerals that form the basis of the technique. For example, reported ages for widely used 40Ar/39Ar reference materials, such as the ca. 28 Ma Fish Canyon Tuff sanidine (FCTs) and the ca. 1.2 Ma Alder Creek Rhyolite sanidine (ACRs), vary by >1%. Recent attempts to independently calibrate these reference minerals have focused on K-Ar analyses of the same minerals and inter-comparisons with astronomically tuned tephras in sedimentary sequences and U-Pb zircon ages from volcanic rocks. Most of these studies used older generation (effectively single-collector) mass spectrometers that employed peak-jumping analytical methods to acquire 40Ar/39Ar data. In this study, we reassess the inter-calibration and ages of commonly used 40Ar/39Ar reference minerals Fish Canyon Tuff sanidine (FCTs), Alder Creek Rhyolite sanidine (ACRs) and Mount Dromedary biotite (MD2b; equivalent to GA-1550 biotite), relative to the astronomically tuned age of A1 Tephra sanidine (A1Ts), Faneromeni section, Crete (Rivera et al., 2011), using a multi-collector ARGUSVI mass spectrometer. These analyses confirm the exceptional precision capability (<0.1%) of this system, compared to most previous studies. All sanidine samples (FCTs, ACRs and A1Ts) exhibit discordant 40Ar/39Ar step-heating spectra, with generally monotonically increasing ages (∼1% gradients). The similarity in these patterns, mass-dependent fractionation modeling, and results from step-crushing experiments on FCTs, which yield younger apparent ages, suggest that the discordance may be due to a combination of recoil loss and redistribution of 39ArK and isotope mass fractionation. In contrast to our previous inferences, these results imply that the sanidine samples are suitable 40Ar/39Ar reference materials, provided appropriate corrections are included for differential recoil loss of 39ArK and contributions from xenocrysts/antecrysts can be resolved. Relative to an age of 6.943 ± 0.005 Ma for A1Ts, we calculate astronomically tuned ages for FCTs, ACRs and MD2b of 28.126 ± 0.019 (0.066%) Ma, 1.18144 ± 0.00068 (0.058%) Ma and 99.125 ± 0.076 (0.077%) Ma, respectively (95% internal errors). These results are consistent with recent 238U/206Pb age data from these localities, but are marginally younger (∼0.2%) than previous 40Ar/39Ar ages inter-calibrated with astronomically tuned tephra from the Mediterranean, and distinctly younger (0.6%) than results optimized against a broad array of 238U/206Pb zircon ages. Consideration of published and assumed recoil loss 39ArK proportions (0.18-0.40%), yields recoil-corrected age estimates of 28.187 ± 0.019 Ma, 1.18404 ± 0.00068 Ma and 99.204 ± 0.076 Ma, respectively. This comparison indicates inherent uncertainties of >0.1% in the 40Ar/39Ar ages of reference minerals without consideration of recoil artefacts, thus limiting the benefits of high precision multi-collector analyses. Significant improvement to the accuracy of the 40Ar/39Ar method (<0.1%) will require further inter-laboratory 40Ar/39Ar studies utilizing multi-collector mass spectrometry, additional constraints on recoil 39ArK loss from reference minerals, further resolution of discrepancies between astronomically tuned sedimentary successions and refinement of the 238U/206Pb zircon age cross-calibration approach.

Risk Factors for Allergic Rhinitis in Costa Rican Children with Asthma

PubMed Central

Bunyavanich, Supinda; Soto-Quiros, Manuel E.; Avila, Lydiana; Laskey, Daniel; Senter, Jody M.; Celedón, Juan C.

2009-01-01

Background Risk factors for allergic rhinitis (AR) in asthmatics are likely distinct from those for AR or asthma alone. We sought to identify clinical and environmental risk factors for AR in children with asthma. Methods We performed a cross-sectional study of 616 Costa Rican children aged 6–14 years with asthma. Candidate risk factors were drawn from questionnaire data, spirometry, methacholine challenge testing, skin testing, and serology. Two outcome measures, skin test reaction (STR)-positive AR and physician-diagnosed AR, were examined by logistic regression. Results STR-positive AR had high prevalence (80%) in Costa Rican children with asthma, and its independent risk factors were nasal symptoms after exposure to dust or mold, parental history of AR, older age at asthma onset, oral steroid use in the past year, eosinophilia, and positive IgEs to dust mite and cockroach. Physician-diagnosed AR had lower prevalence (27%), and its independent risk factors were nasal symptoms after pollen exposure, STR to tree pollens, a parental history of AR, inhaled steroid and short-acting β2 agonist use in the past year, household mold/mildew, and fewer older siblings. A physician’s diagnosis was only 29.5% sensitive for STR-positive AR. Conclusions Risk factors for AR in children with asthma depend on the definition of AR. Indoor allergens drive risk for STR-positive AR. Outdoor allergens and home environmental conditions are risk factors for physician-diagnosed AR. We propose that children with asthma in Costa Rica and other Latin American nations undergo limited skin testing or specific IgE measurements to reduce the current under-diagnosis of AR. PMID:19796208

Structural basis for cyclization specificity of two Azotobacter type III polyketide synthases: a single amino acid substitution reverses their cyclization specificity.

PubMed

Satou, Ryutaro; Miyanaga, Akimasa; Ozawa, Hiroki; Funa, Nobutaka; Katsuyama, Yohei; Miyazono, Ken-ichi; Tanokura, Masaru; Ohnishi, Yasuo; Horinouchi, Sueharu

2013-11-22

Type III polyketide synthases (PKSs) show diverse cyclization specificity. We previously characterized two Azotobacter type III PKSs (ArsB and ArsC) with different cyclization specificity. ArsB and ArsC, which share a high sequence identity (71%), produce alkylresorcinols and alkylpyrones through aldol condensation and lactonization of the same polyketomethylene intermediate, respectively. Here we identified a key amino acid residue for the cyclization specificity of each enzyme by site-directed mutagenesis. Trp-281 of ArsB corresponded to Gly-284 of ArsC in the amino acid sequence alignment. The ArsB W281G mutant synthesized alkylpyrone but not alkylresorcinol. In contrast, the ArsC G284W mutant synthesized alkylresorcinol with a small amount of alkylpyrone. These results indicate that this amino acid residue (Trp-281 of ArsB or Gly-284 of ArsC) should occupy a critical position for the cyclization specificity of each enzyme. We then determined crystal structures of the wild-type and G284W ArsC proteins at resolutions of 1.76 and 1.99 Å, respectively. Comparison of these two ArsC structures indicates that the G284W substitution brings a steric wall to the active site cavity, resulting in a significant reduction of the cavity volume. We postulate that the polyketomethylene intermediate can be folded to a suitable form for aldol condensation only in such a relatively narrow cavity of ArsC G284W (and presumably ArsB). This is the first report on the alteration of cyclization specificity from lactonization to aldol condensation for a type III PKS. The ArsC G284W structure is significant as it is the first reported structure of a microbial resorcinol synthase.

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Advancements in cosmogenic 38Ar exposure dating of terrestrial rocks

NASA Astrophysics Data System (ADS)

Oostingh, K. F.; Jourdan, F.; Danišík, M.; Evans, N. J.

2017-11-01

Cosmogenic exposure dating of Ca-rich minerals using 38Ar on terrestrial rocks could be a valuable new dating tool to determine timescales of geological surface processes on Earth. Here, we show that advancement in analytical precision, using the new generation multi-collector ARGUSVI mass spectrometer on irradiated pyroxene and apatite samples, allows determination of cosmogenic 38Ar abundances above background values, as well as discrimination of 38Ar/36Ar ratios (1σ absolute precision of ±0.3%) from the non-cosmogenic background value. Four statistically significant cosmochron (38Ar/36Ar vs37Ar/36Ar) diagrams could be constructed for southeast Australian pyroxene samples from the Mt Elephant scoria cone for which a combined apparent exposure age of 313 ± 179 ka (2σ) was obtained when using a 38Ar production rate (Ca) of 250 atoms /g Ca/ yr. This exposure age overlaps within error with the known 40Ar/39Ar eruption age of 184 ± 15 ka (2σ). Although apatite shows much larger 38Ar abundances than pyroxene, our modelling and analyses of unirradiated apatite suggest that apatite suffers from both natural and reactor-derived chlorogenic as well as natural nucleogenic contributions of 38Ar. Hence, we suggest that cosmogenic 38Ar exposure dating on irradiated Ca-rich (and eventually K-rich), but Cl-free, terrestrial minerals is a potential valuable and accessible tool to determine geological surface processes on timescales of a few Ma. Calculations show that with the new generation multi-collector mass spectrometers an analytical uncertainty better than 5% (2σ) can be achieved on samples with expected exposure ages of >4 Ma.

Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells.

PubMed

Bhattacharyya, Rumi S; Krishnan, Aruna V; Swami, Srilatha; Feldman, David

2006-06-01

The androgen receptor (AR) plays a key role in the development and progression of prostate cancer. Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory or androgen-independent prostate cancer. In the present study, we showed that the antiestrogen fulvestrant [ICI 182,780 (ICI)] effectively suppressed AR expression in several human prostate cancer cells, including androgen-independent cells. In LNCaP cells, ICI (10 micromol/L) treatment decreased AR mRNA expression by 43% after 24 hours and AR protein expression by approximately 50% after 48 hours. We further examined the mechanism of AR down-regulation by ICI in LNCaP cells. ICI did not bind to the T877A-mutant AR present in the LNCaP cells nor did it promote proteasomal degradation of the AR. ICI did not affect AR mRNA or protein half-life. However, ICI decreased the activity of an AR promoter-luciferase reporter plasmid transfected into LNCaP cells, suggesting a direct repression of AR gene transcription. As a result of AR down-regulation by ICI, androgen induction of prostate-specific antigen mRNA and protein expression were substantially attenuated. Importantly, LNCaP cell proliferation was significantly inhibited by ICI treatment. Following 6 days of ICI treatment, a 70% growth inhibition was seen in androgen-stimulated LNCaP cells. These data show that the antiestrogen ICI is a potent AR down-regulator that causes significant inhibition of prostate cancer cell growth. Our study suggests that AR down-regulation by ICI would be an effective strategy for the treatment of all prostate cancer, especially AR-dependent androgen-independent prostate cancer.

Probing Subsurface Flows in NOAA Active Region 12192: Comparison with NOAA 10486

NASA Astrophysics Data System (ADS)

Jain, Kiran; Tripathy, S. C.; Hill, F.

2017-11-01

NOAA Active Region (AR) 12192 is the biggest AR observed in solar cycle 24 so far. This was a long-lived AR that survived for four Carrington rotations (CRs) and exhibited several unusual phenomena. We measure the horizontal subsurface flows in this AR in multiple rotations using the ring-diagram technique of local helioseismology and the Global Oscillation Network Group (GONG+) Dopplergrams, and we investigate how different was the plasma flow in AR 12192 from that in AR 10486. Both regions produced several high M- and X-class flares, but they had different coronal mass ejection (CME) productivity. Our analysis suggests that these ARs had unusually large horizontal flow amplitude with distinctly different directions. While meridional flow in AR 12192 was poleward that supports the flux transport to poles, it was equatorward in AR 10486. Furthermore, there was a sudden increase in the magnitude of estimated zonal flow in shallow layers in AR 12192 during the X3.1 flare; however, it reversed direction in AR 10486 with the X17.2 flare. These flow patterns produced strong twists in horizontal velocity with depth in AR 10486 that persisted throughout the disk passage, as opposed to AR 12192, which produced a twist only after the eruption of the X3.1 flare that disappeared soon after. Our study indicates that the sunspot rotation combined with the reorganization of magnetic field in AR 10486 was not sufficient to decrease the flow energy even after several large flares that might have triggered CMEs. Furthermore, in the absence of sunspot rotation in AR 12192, this reorganization of magnetic field contributed significantly to the substantial release of flow energy after the X3.1 flare.

Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer.

PubMed

Li, Bo; Lu, Wenfu; Yang, Qing; Yu, Xiuping; Matusik, Robert J; Chen, Zhenbang

2014-04-01

The intervention of advanced prostate cancer (PCa) in patients has been commonly depending on androgen deprivation therapy. Despite of tremendous research efforts, however, molecular mechanisms on AR regulation remain poorly understood, particularly for castration resistant prostate cancer (CRPC). Targeting AR and associated factors is considered an effective strategy in PCa treatment. Human prostate cancer cells were used in this study. Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or overexpression of plasmids. Dual luciferase reporter assay was applied for AR activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and immunofluorescence were applied to detect the proteins. Our results demonstrated that Skp2 directly involves the regulation of AR expression through ubiquitination-mediated degradation. Skp2 interacted with AR protein in PCa cells, and enforced expression of Skp2 resulted in a decreased level and activity of AR. By contrast, Skp2 knockdown increased the protein accumulation and activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent alterations of PSA level in PCa cells. AR ubiquitination was significantly increased upon Skp2 overexpression but greatly reduced upon Skp2 knockdown. AR mutant at K847R abrogated Skp2-mediated ubiquitination of AR. NVP-BEZ235, a dual PI3K/mTOR inhibitor, remarkably inhibited Skp2 level with a striking elevation of AR. The results indicate that Skp2 is an E3 ligase for proteasome-dependent AR degradation, and K847 on AR is the recognition site for Skp2-mediated ubiquitination. Our findings reveal an essential role of Skp2 in AR signaling. © 2013 Wiley Periodicals, Inc.

Identification of Novel Transplantable GPCR Recycling Motif for Drug Discovery

PubMed Central

Nooh, Mohammed M.; Mancarella, Salvatore; Bahouth, Suleiman W.

2016-01-01

β1-adrenergic receptor (β1-AR) agonists and antagonists are widely used in the treatment of major cardiovascular diseases such as heart failure and hypertension. The β1-AR like other G protein-couple receptors (GPCR) is endocytosed in response to intense agonist activation. Recycling of the agonist-internalized β1-AR is dependent on its carboxy-terminal type-1 PSD-95/DLG/ZO1 (PDZ) and on phospho-serine312 in the third intracellular loop of the β1-AR. Progressive elongation of the β1-AR at its C-tail inactivated the PDZ-biding domain and inhibited the recycling of the β1-AR. However, fusing a twenty amino acid peptide derived from the multiple cloning region of the mammalian expression vector pCDNA3 to the C-tail of the β1-AR (β1-AR[+20]) produced a chimeric β1-AR that recycled rapidly and efficiently. The β1-AR[+20] recycled in a type-1 PDZ and phospho-Ser312-independent manner, indicating that this peptide provided a general GPCR recycling signal. Fusing the enhanced yellow fluorescent protein (EYFP) down-stream of β1-AR[+20] generated a β1-AR-EYFP chimera that was expressed on the membrane and recycled efficiently after agonist-induced internalization. This construct trafficked in a PDZ-SNX27/retromer-independent manner. We also fused EYFP to the N-terminus of the β1-AR to created EYFP-WT β1-AR. This construct recycled in PDZ and SNX27/retromer dependent manner. These β1-AR-EYFP constructs would be useful for high throughput screening (HTS) programs to identify new entities that would interfere with the recycling of agonist internalized GPCR that traffic in PDZ-dependent vs. PDZ-independent roadmaps. PMID:27645110

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

PubMed

Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

2016-03-03

Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

In-situ Ar isotope, 40Ar/39Ar analysis and mineral chemistry of nosean in the phonolite from Olbrück volcano, East Eifel volcanic field, Germany: Implication for the source of excess 40Ar

NASA Astrophysics Data System (ADS)

Sudo, Masafumi; Altenberger, Uwe; Günter, Christina

2014-05-01

Since the report by Lippolt et al. (1990), hauyne and nosean phenocrysts in certain phonolites from the northwest in the Quaternary East Eifel volcanic field in Germany were known to contain significant amounts of excess 40Ar, thus, show apparent older ages than the other minerals. However, its petrographic meaning have not been well known. Meanwhile, Sumino et al. (2008) has identified the source of the excess 40Ar in the plagioclase phenocrysts from the historic Unzen dacite lava as the melt inclusions in the zones parallely developed to the plagioclase rim by in-situ laser Ar isotope analysis. In order to obtain eruption ages of very young volcanoes as like Quaternary Eifel volcanic field by the K-Ar system, it is quite essential to know about the location of excess 40Ar in volcanic rocks. We have collected phonolites from the Olbrück volcano in East Eifel and investigated its petrography and mineral chemistry and also performed in-situ Ar isotope analyses of unirradiated rock section sample and also in-situ 40Ar/39Ar analysis of neutron irradiated section sample with the UV pulse laser (wavelength 266 nm) and 40Ar/39Ar analytical system of the University of Potsdam. Petrographically, nosean contained fine melt and/or gas inclusions of less than 5 micrometer, which mostly distribute linearly and are relatively enriched in chlorine than the areas without inclusions. Solid inclusions of similar sizes contain CaO and fluorine. In nosean, typically around 5 wt% of sulfur is contained. The 40Ar/39Ar dating was also performed to leucite, sanidine and groundmass in the same section for comparison of those ages with that of nosean. In each analysis, 200 micrometer of beam size was used for making a pit with depth of up to 300 micrometer by laser ablation. As our 40Ar/39Ar analyses were conducted one and half year after the neutron irradiation, thus, short lived 37Ar derived from Ca had decayed very much, we measured Ca and K contents in nosean by SEM-EDS then applied their Ca/K ratios to the Ar analytical results. The in-situ Ar isotopic analysis of nosean and leucite show clearly the different slope of isochron and implied apparent older age for the nosean. The in-situ 40Ar/39Ar analysis of nosean yields three various ages, from 6.86 ± 2.77 Ma to 41.57 ± 11.58 Ma, but clearly older than those of the other minerals and groundmass. However, it was difficult to analyze and compare the 40Ar/39Ar ages between different areas with or without inclusions by the UV-laser because of its less spatial resolution, therefore, was difficult to understand the correlation between ages and the presence of inclusions. Considering the enriched contents of S and Cl in nosean, the excess 40Ar could be derived from the common volatile component separated from the magma which provided S and Cl then be trapped in nosean during or after the formation of nosean. References: Lippolt, H. J., M. Troesch and J. C. Hess (1990) Earth Planet. Sci. Lett., 101, 19-33 Sumino, H., K. Ikehata, A. Shimizu, K. Nagao and S. Nakada (2008) J. Volcanol. Geotherm. Res., 175, 189-207

Ar-39-Ar-40 Ages of Euerites and the Thermal History of Asteroid 4-Vesta

NASA Technical Reports Server (NTRS)

Bogard, Donald D.; Garrison, Daniel H.

2002-01-01

Eucrite meteorites are igneous rocks that derive from a large asteroid, probably 4 Vesta. Prior studies have shown that after eucrites formed, most were subsequently metamorphosed to temperatures up to equal to or greater than 800 C, and much later many were brecciated and heated by large impacts into the parent body surface. The uncommon basaltic, unbrecciated eucrites also formed near the surface but presumably escaped later brecciation, whereas the cumulate eucrites formed at depth where metamorphism may have persisted for a considerable period. To further understand the complex HED parent body thermal history, we determined new Ar-39-Ar-40 ages for nine eucrites classified as basaltic but unbrecciated, six eucrites classified as cumulate, and several basaltic-brecciated eucrites. Relatively precise Ar-Ar ages of two cumulate eucrites (Moama and EET87520) and four unbrecciated eucrites give a tight cluster at 4.48 +/1 0.01 Gyr. Ar-Ar ages of six additional unbrecciated eucrites are consistent with this age, within their larger age uncertainties. In contrast, available literature data on Pb-Pb isochron ages of four cumulate eucrites and one unbrecciated eucrite vary over 4.4-4.515 Gyr, and Sm-147 - Nd-143 isochron ages of four cumulate and three unbrecciated eucrites vary over 4.41-4.55 Gyr. Similar Ar-Ar ages for cumulate and unbrecciated eucrites imply that cumulate eucrites do not have a younger formation age than basaltic eucrites, as previously proposed. Rather, we suggest that these cumulate and unbrecciated eucrites resided at depth where parent body temperatures were sufficiently high to cause the K-Ar and some other chronometers to remain open diffusion systems. From the strong clustering of Ar-Ar ages at approximately 4.48 Gyr, we propose that these meteorites were excavated from depth in a single large impact event approximately 4.48 Gyr ago, which quickly cooled the samples and started the K-Ar chronometer. A large (approximately 460 km) crater postulated to exist on Vesta may be the source of these eucrites and of many smaller asteroids thought to be spectrally or physically associated with Vesta. Some Pb-Pb and Sm-Nd ages of cumulate and unbrecciated eucrites are consistent with the 4.48 Gyr Ar-Ar age, and the few older Pb-Pb and Sm-Nd ages may reflect isotopic closure prior to the large cratering event. One cumulate eucrite gives an Ar-Ar age of 4.25 Gyr; three additional cumulate eucrites give Ar-Ar ages of 3.4-3.7 Gyr; and two unbrecciated eucrites give Ar-Ar ages of approximately 3.55 Gyr. We attribute these younger ages to later impact heating. In addition, we find Ar-Ar impact-reset ages of several brecciated eucrites and eucritic clasts in howardites to fall in the range of 3.5-4.1 Gyr. Among these, Piplia Kalan, the first eucrite to show evidence for extinct 26 Al, was strongly impact heated approximately3.5 Gyr ago. When these data are combined with eucrite Ar-Ar ages in the literature, they confirm the previous suggestion that several large impact heating events occurred on Vesta over the time period approximately 4.1-3.4 Gyr ago. The onset of major impact heating may have occurred at similar times for both Vesta and the Moon, but impact heating appears to have persisted to a somewhat later time on Vesta compared to the Moon.

The Role of Tropical Moisture Export on Atmospheric River Intensity

NASA Astrophysics Data System (ADS)

Hu, H.; Dominguez, F.

2017-12-01

There has been considerable debate regarding the relative importance of tropical moisture export (TME) and local evapotranspiration on the total moisture associated with atmospheric rivers (ARs). While case studies have related TME signatures with some extreme ARs affecting the U.S. West Coast, no robust relationship between them has been established. In this study, our goal is to quantify the role of TME on AR-related precipitation intensity. From a total of 244 identified ARs that have affected the U.S. Northwest Coast in winters of 1979 to 2016, we are focusing on a subset of 37 ARs with TME features (TME-ARs). These TME-ARs are identified using vapor-weighted wind vectors to back-track ARs 3 days before they reach the Northwest Coast. If their back-trajectories reach latitudes south of 25°N, the AR is labeled as a TME-AR. Compared with the rest of ARs without TME features, TME-ARs are associated with higher vertically integrated vapor transport (IVT) and greater precipitation intensity. At the same time, they also span a wide range of precipitation intensity and thus allow an examination of the TME effect on a full spectrum of AR intensity. To quantify the effect of TME on AR-related precipitable water and precipitation, we simulate the 37 TME-ARs using the tool of water vapor tracer in WRF model (WRF-WVT) to tag the moisture evaporated from latitudes lower than 25°N. Consequently, the total moisture can be separated into that from TME and that from midlatitude evaporation. Our analysis shows that as the AR gets stronger in terms of total precipitable water and precipitation, there is a significant increase of the contribution from TME to total precipitable water. Similarly, the contribution from TME to AR precipitation also increases but with a weaker correlation. Both of them suggest an increasing role of TME on more intense ARs. We also find a higher efficiency of TME moisture being converted to precipitation than that from local sources. However, this efficiency decreases when AR precipitation intensity increases, suggesting an increasing role of local (midlatitude) evaporation in generating precipitation. This is probably due to the thermodynamic changes associated with TME, which enhances local circulation and thus local moisture recycling.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

PubMed

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-11-09

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

32 CFR 552.107 - References.

Code of Federal Regulations, 2010 CFR

2010-07-01

... References. (a) AR 190-5 (Motor Vehicle Traffic Supervision) (b) AR 190-52 (Countering Terrorism and Other Major Disruptions on Military Reservations) (c) AR 210-7 (Commercial Solicitation on Army Installations) (d) AR 210-10 (Administration) (e) Fort Lewis Supplement 1 to AR 190-5 (Motor Vehicle Traffic...

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands.

PubMed

Shibata, Norihito; Nagai, Katsunori; Morita, Yoko; Ujikawa, Osamu; Ohoka, Nobumichi; Hattori, Takayuki; Koyama, Ryokichi; Sano, Osamu; Imaeda, Yasuhiro; Nara, Hiroshi; Cho, Nobuo; Naito, Mikihiko

2018-01-25

Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named specific and nongenetic inhibitor of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show novel SNIPERs capable of inducing proteasomal degradation of the androgen receptor (AR). Through derivatization of the SNIPER(AR) molecule at the AR ligand and IAP ligand and linker, we developed 42a (SNIPER(AR)-51), which shows effective protein knockdown activity against AR. Consistent with the degradation of the AR protein, 42a inhibits AR-mediated gene expression and proliferation of androgen-dependent prostate cancer cells. In addition, 42a efficiently induces caspase activation and apoptosis in prostate cancer cells, which was not observed in the cells treated with AR antagonists. These results suggest that SNIPER(AR)s could be leads for an anticancer drug against prostate cancers that exhibit AR-dependent proliferation.

An Interdomain Interaction of the Androgen Receptor Is Required for Its Aggregation and Toxicity in Spinal and Bulbar Muscular Atrophy*

PubMed Central

Orr, Christopher R.; Montie, Heather L.; Liu, Yuhong; Bolzoni, Elena; Jenkins, Shannon C.; Wilson, Elizabeth M.; Joseph, James D.; McDonnell, Donald P.; Merry, Diane E.

2010-01-01

Polyglutamine expansion within the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA) and is associated with misfolded and aggregated species of the mutant AR. We showed previously that nuclear localization of the mutant AR was necessary but not sufficient for SBMA. Here we show that an interdomain interaction of the AR that is central to its function within the nucleus is required for AR aggregation and toxicity. Ligands that prevent the interaction between the amino-terminal FXXLF motif and carboxyl-terminal AF-2 domain (N/C interaction) prevented toxicity and AR aggregation in an SBMA cell model and rescued primary SBMA motor neurons from 5α-dihydrotestosterone-induced toxicity. Moreover, genetic mutation of the FXXLF motif prevented AR aggregation and 5α-dihydrotestosterone toxicity. Finally, selective androgen receptor modulators, which prevent the N/C interaction, ameliorated AR aggregation and toxicity while maintaining AR function, highlighting a novel therapeutic strategy to prevent the SBMA phenotype while retaining AR transcriptional function. PMID:20826791

ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.

PubMed

Mounir, Zineb; Korn, Joshua M; Westerling, Thomas; Lin, Fallon; Kirby, Christina A; Schirle, Markus; McAllister, Gregg; Hoffman, Greg; Ramadan, Nadire; Hartung, Anke; Feng, Yan; Kipp, David Randal; Quinn, Christopher; Fodor, Michelle; Baird, Jason; Schoumacher, Marie; Meyer, Ronald; Deeds, James; Buchwalter, Gilles; Stams, Travis; Keen, Nicholas; Sellers, William R; Brown, Myles; Pagliarini, Raymond A

2016-05-16

The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells. Mutation of this methylation site on AR results in a transcriptionally hyperactive AR, suggesting that the proliferative effects of ERG and PRMT5 are mediated through attenuating AR's ability to induce genes normally involved in lineage differentiation. This provides a rationale for targeting PRMT5 in TMPRSS2:ERG positive prostate cancers. Moreover, methylation of AR at arginine 761 highlights a mechanism for how the ERG oncogene may coax AR towards inducing proliferation versus differentiation.

Structures, bonding, and reaction chemistry of the neutral organogallium(I) compounds (GaAr)n(n = 1 or 2) (Ar = terphenyl or related ligand): an experimental investigation of Ga-Ga multiple bonding.

PubMed

Hardman, Ned J; Wright, Robert J; Phillips, Andrew D; Power, Philip P

2003-03-05

The synthesis, structure, and properties of several new organogallium(I) compounds are reported. The monovalent compounds GaAr* (Ar* = C(6)H(3)-2,6-Trip(2), Trip = C(6)H(2)-2,4,6-Pr(i)()(3), 1), GaAr# (Ar# = C(6)H(3)-2,6(Bu(t)Dipp)(2), Bu(t)Dipp = C(6)H(2)-2,6-Pr(i)(2)-4-Bu(t)(), 4), and the dimeric (GaAr')(2) (Ar' = C(6)H(3)-2,6-Dipp(2), Dipp = C(6)H(3)-2,6-Pr(i)(2), 6) were synthesized by the reaction of "GaI" with (Et(2)O)LiAr*, (Et(2)O)LiAr# (3), or (LiAr')(2). Compounds 1 and 4 were isolated as green crystals, whereas 6 was obtained as a brown-red crystalline solid. All three compounds dissolved in hydrocarbon solvents to give green solutions and almost identical UV/visible spectra. Cryoscopy of 1 and 6 showed that they were monomeric in cyclohexane. Crystals of 1 and 4 were unsuitable for X-ray crystal structure determinations, but an X-ray data set for 6 showed that it was weakly dimerized in the solid with a long Ga-Ga bond of 2.6268(7) A and a trans-bent CGaGaC core array. The 1,2-diiodo-1,2-diaryldigallane compounds [Ga(Ar*)I](2) (2), [Ga(Ar#)I](2) (5), and [Ga(Ar')I](2) (7) were isolated as byproducts of the synthesis of 1, 4, and 6. The crystal structures of 2 and 7 showed that they had planar ICGaGaCI core arrays with Ga-Ga distances near 2.49 A, consistent with Ga-Ga single bonding. Treatment of 1, 4, and 6 with B(C(6)F(5))(3) immediately afforded the 1:1 donor-acceptor complexes ArGa[B(C(6)F(5))(3)] (Ar = Ar*, 8; Ar#, 9; Ar', 10) that featured almost linear gallium coordination, Ga-B distances near the sum of the covalent radii of gallium and boron, as well as some close Ga...F contacts. Compound 1 also reacted with Fe(CO)(5) under ambient conditions to give Ar*GaFe(CO)(4) (11), which had been previously synthesized by the reaction of GaAr*Cl(2) with Na(2)Fe(CO)(4). Reaction of 1 with 2,3-dimethyl-1,3-butadiene afforded the compound [Ar*GaCH(2)C(Me)C(Me)CH(2)]2 (12) that had a 10-membered 1,5-Ga(2)C(8) ring with no Ga-Ga interaction. Stirring 1 or 6 with sodium readily gave Na(2)[Ar*GaGaAr*] (13) and Na(2)(Ar'GaGaAr') (14). The former species 13 had been synthesized previously by reduction of GaAr*Cl(2) with sodium and was described as having a Ga-Ga triple bond because of the short Ga-Ga distance and the electronic relationship between [Ar*GaGaAr*](2-) and the corresponding neutral group 14 alkyne analogues. Compound 14 has a similar structure featuring a trans-bent CGaGaC core, bridged by sodiums which were also coordinated to the flanking aryl rings of the Ar' ligands. The Ga-Ga bond length was found to be 2.347(1) A, which is slightly (ca. 0.02 A) longer than that reported for 13. Reaction of Ga[N(Dipp)C(Me)](2)CH, 15 (i.e., GaN(wedge)NDipp(2)), which is sterically related to 1, 4, and 6, with Fe(CO)(5) yielded Dipp(2)N(wedge)NGaFe(CO)(4) (16), whose Ga-Fe bond is slightly longer than that observed in 11. Reaction of the less bulky LiAr"(Ar"= C(6)H(3)-2,6-Mes(2)) with "GaI" afforded the new paramagnetic cluster Ga(11)Ar(4)" (17). The ready dissociation of 1, 4, and 6 in solution, the long Ga-Ga distance in 6, and the chemistry of these compounds showed that the Ga-Ga bonds are significantly weaker than single bonds. The reduction of 1 and 6 with sodium to give 13 and 14 supplies two electrons to the di-gallium unit to generate a single bond (in addition to the weak interaction in the neutral precursor) with retention of the trans-bent geometry. It was concluded that the stability of 13 and 14 depends on the matching size of the sodium ion, and the presence of Na-Ga and Na-Ar interactions that stabilize their Na(2)Ga(2) core structures.

Tissue-specific distribution of the androgen receptor (AR) in the porcine fetus.

PubMed

Burek, Małgorzata; Duda, Małgorzata; Knapczyk, Katarzyna; Koziorowski, Marek; Słomczyńska, Maria

2007-01-01

The aim of this study was to investigate androgen receptor (AR) expression in developing porcine fetuses. The localization of AR was examined on embryos obtained at different days of gestation: days 18, 32, 50, 71, 90 post coitum (p.c.), and in the several tissues collected from the newborn piglets of both sexes. AR expression was first observed on day 32 p.c. in the mesonephron region. RT-PCR did not show AR mRNA on day18 p.c., but the message was present starting from day 32. In the male differentiating gonads and in the male genital ducts AR protein was present at 50, 71 and 90 days of gestation. AR protein was also detected in the cords of stromal cells within the medulla of the ovary and in stromal cells investing the oogonial nests. Pregranulosa cells on day 90 of gestation and on day 1 post partum (p.p.) immunolabelled positively for AR. In the kidney, a number of AR-positive tubules were visible while the mesenchyme in the kidney was AR-negative. Immunoreactive AR was detected predominantly in the nuclei of epithelial cells of the budding component at different stages of gestation of porcine lung. The presence of AR during gestation in non-gonadal tissues suggests a role of androgen in these tissues.

MEIS1 functions as a potential AR negative regulator

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

Cui, Liang; Department of Urology, Civil Aviation General Hospital/Civil Aviation Medical College of Peking University, Beijing 100123; Li, Mingyang

2014-10-15

The androgen receptor (AR) plays critical roles in human prostate carcinoma progression and transformation. However, the activation of AR is regulated by co-regulators. MEIS1 protein, the homeodomain transcription factor, exhibited a decreased level in poor-prognosis prostate tumors. In this study, we investigated a potential interaction between MEIS1 and AR. We found that overexpression of MEIS1 inhibited the AR transcriptional activity and reduced the expression of AR target gene. A potential protein–protein interaction between AR and MEIS1 was identified by the immunoprecipitation and GST pull-down assays. Furthermore, MEIS1 modulated AR cytoplasm/nucleus translocation and the recruitment to androgen response element in prostatemore » specific antigen (PSA) gene promoter sequences. In addition, MEIS1 promoted the recruitment of NCoR and SMRT in the presence of R1881. Finally, MEIS1 inhibited the proliferation and anchor-independent growth of LNCaP cells. Taken together, our data suggests that MEIS1 functions as a novel AR co-repressor. - Highlights: • A potential interaction was identified between MEIS1 and AR signaling. • Overexpression of MEIS1 reduced the expression of AR target gene. • MEIS1 modulated AR cytoplasm/nucleus translocation. • MEIS1 inhibited the proliferation and anchor-independent growth of LNCaP cells.« less

Endoglucanase and xylanase production by Bacillus sp. AR03 in co-culture.

PubMed

Hero, Johan S; Pisa, José H; Perotti, Nora I; Romero, Cintia M; Martínez, María A

2017-07-03

The behavior of three isolates retrieved from different cellulolytic consortia, Bacillus sp. AR03, Paenibacillus sp. AR247 and Achromobacter sp. AR476-2, were examined individually and as co-cultures in order to evaluate their ability to produce extracellular cellulases and xylanases. Utilizing a peptone-based medium supplemented with carboxymethyl cellulose (CMC), an increase estimation of 1.30 and 1.50 times was obtained by the co-culture containing the strains AR03 and AR247, with respect to enzyme titles registered by their individual cultivation. On the contrary, the extracellular enzymatic production decreased during the co-cultivation of strain AR03 with the non-cellulolytic Achromobacter sp. AR476-2. The synergistic behavior observed through the combined cultivation of the strains AR03 and AR247 might be a consequence of the consumption by Paenibacillus sp. AR247 of the products of the CMC hydrolysis (i.e., cellobiose and/or cello-oligosaccharides), which were mostly generated by the cellulase producer Bacillus sp. AR03. The effect observed could be driven by the requirement to fulfill the nutritional supply from both strains on the substrate evaluated. These results would contribute to a better description of the degradation of the cellulose fraction of the plant cell walls in nature, expected to an efficient utilization of renewable sources.

Ar-40/Ar-39 Studies of Martian Meteorite RBT 04262 and Terrestrial Standards

NASA Technical Reports Server (NTRS)

Park, J.; Herzog, G. F.; Turrin, B.; Lindsay, F. N.; Delaney, J. S.; Swisher, C. C., III; Nagao, K.; Nyquist, L. E.

2014-01-01

Park et al. recently presented an Ar-40/Ar-39 dating study of maskelynite separated from the Martian meteorite RBT 04262. Here we report an additional study of Ar-40/Ar-39 patterns for smaller samples, each consisting of only a few maskelynite grains. Considered as a material for Ar-40/Ar-39 dating, the shock-produced glass maskelynite has both an important strength (relatively high K concentration compared to other mineral phases) and some potentially problematic weaknesses. At Rutgers, we have been analyzing small grains consisting of a single phase to explore local effects that might be averaged and remain hidden in larger samples. Thus, to assess the homogeneity of the RBT maskelynite and for comparison with the results of, we analyzed six approx. 30 microgram samples of the same maskelynite separate they studied. Furthermore, because most Ar-40/Ar-39 are calculated relative to the age of a standard, we present new Ar-40/Ar-39 age data for six standards. Among the most widely used standards are sanidine from Fish Canyon (FCs) and various hornblendes (hb3gr, MMhb-1, NL- 25), which are taken as primary standards because their ages have been determined by independent, direct measurements of K and A-40.

Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells

PubMed Central

Chang, Chawnshang; Yeh, Shuyuan; Lee, Soo Ok; Chang, Ta-min

2013-01-01

The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases. PMID:24653668

Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms.

PubMed

Carlin, Jesse Lea; Jain, Shalini; Gizewski, Elizabeth; Wan, Tina C; Tosh, Dilip K; Xiao, Cuiying; Auchampach, John A; Jacobson, Kenneth A; Gavrilova, Oksana; Reitman, Marc L

2017-03-01

Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1 -/- , Adora3 -/- ) mice. Confirming prior data, stimulation of the A 3 adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H 1 receptors. In contrast, A 1 AR agonists and AMP both acted centrally to cause hypothermia. Commonly used, selective A 1 AR agonists, including N 6 -cyclopentyladenosine (CPA), N 6 -cyclohexyladenosine (CHA), and MRS5474, caused hypothermia via both A 1 AR and A 3 AR when given intraperitoneally. Intracerebroventricular dosing, low peripheral doses of Cl-ENBA [(±)-5'-chloro-5'-deoxy-N 6 -endo-norbornyladenosine], or using Adora3 -/- mice allowed selective stimulation of A 1 AR. AMP-stimulated hypothermia can occur independently of A 1 AR, A 3 AR, and mast cells. A 1 AR and A 3 AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A 1 AR nor A 3 AR was required for fasting-induced torpor. A 1 AR and A 3 AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms. Published by Elsevier Ltd.

Expression profiles and functional associations of endogenous androgen receptor and caveolin-1 in prostate cancer cell lines.

PubMed

Bennett, Nigel C; Hooper, John D; Johnson, David W; Gobe, Glenda C

2014-05-01

In prostate cancer (PCa) patients, the protein target for androgen deprivation and blockade therapies is androgen receptor (AR). AR interacts with many proteins that function to either co-activate or co-repress its activity. Caveolin-1 (Cav-1) is not found in normal prostatic epithelium, but is found in PCa, and may be an AR co-regulator protein. We investigated cell line-specific signatures and associations of endogenous AR and Cav-1 in six PCa cell lines of known androgen sensitivity: LNCaP (androgen sensitive); 22Rv1 (androgen responsive); PC3, DU145, and ALVA41 (androgen non-reliant); and RWPE1 (non-malignant). Protein and mRNA expression profiles were compared and electron microscopy used to identify cells with caveolar structures. For cell lines expressing both AR and Cav-1, knockdown techniques using small interfering RNA against AR or Cav-1 were used to test whether diminished expression of one affected the other. Co-sedimentation of AR and Cav-1 was used to test their association. A reporter assay for AR genomic activity was utilized following Cav-1 knockdown. AR-expressing LNCaP and 22Rv1 cells had low endogenous Cav-1 mRNA and protein. Cell lines that expressed little or no AR (DU145, PC3, ALVA41, and RWPE1) expressed high endogenous levels of Cav-1. AR knockdown in LNCaP cells had little effect on Cav-1, but Cav-1 knockdown inhibited AR expression and genomic activity. These data show endogenous AR and Cav-1 mRNA and protein expression is inversely related in PCa cells, with Cav-1 acting on the androgen/AR signaling axis possibly as an AR co-activator, demonstrated by diminished AR genomic activity following Cav-1 knockdown. © 2013 Wiley Periodicals, Inc.

Measuring 36Ar without H35Cl interference

NASA Astrophysics Data System (ADS)

Saxton, John

2015-04-01

Noble gas measurements are usually made in static mode, when the mass spectrometer sensitivity is inversely proportional to volume: this makes the building of very large instruments to obtain high mass resolution impracticable. A particularly challenging interference has hitherto been H35Cl, which differs in mass from 36Ar by 1 part in 3937. We have developed a method which makes improved use of the available MRP to remove interferences, and used it to obtain HCl-free 36Ar measurements on a multicollector instrument with MRP of only ~6000 (MRP= mass resolving power = m/dm 5-95% on side of peak). By arranging that the target mass position on a minor isotope (e.g. 36Ar), from which the interference must be removed, coincides with the ~50% point on the side of a major isotope (e.g. 40Ar), it is possible both to set the mass accurately and to verify the mass position and stability during measurements. The peak top of 40Ar is measured in a separate mass step. Two small corrections are necessary. One compensates for the residual HCl tail at the 36Ar position. The other arises because the peak is not totally flat in the region of interest: 40Ar and 36Ar+HCl are measured on the peak top, whilst 36Ar is measured at the extreme edge, with slightly lower efficiency. The required correction parameters can be obtained from a series of air calibrations with different target/interference ratios. With samples containing 4x10-15to 3x10-14moles of 40Ar, 36Ar/40Ar was measured, without HCl interference, to a 1σ precision of 0.5%, only slightly worse than counting statistics. This is potentially useful for 40Ar/39Ar dating, where 36Ar is used to correct for trapped air, and may be particularly significant for smaller or younger samples.

Interrelation of androgen receptor and miR-30a and miR-30a function in ER-, PR-, AR+ MDA-MB-453 breast cancer cells.

PubMed

Lyu, Shuhua; Liu, Han; Liu, Xia; Liu, Shan; Wang, Yahong; Yu, Qi; Niu, Yun

2017-10-01

The association between androgen-induced androgen receptor (AR) activating signal and microRNA (miR)-30a was investigated, as well as the function of miR-30a in estrogen receptor-negative (ER - ), progesterone receptor-negative (PR - ), and AR-positive (AR + ) MDA-MB-453 breast cancer cells. Androgen-induced AR activating signal upregulated the expression of AR, and downregulated the expression of miR-30a, b and c. Bioinformatics analysis indicated a putative miR-30a, b and c binding site in the 3'-untranslated region of AR mRNA. It was confirmed that the AR gene is a direct target of miR-30a, whereas AR does not target the miR-30a promoter, and AR activating signal may indirectly downregulate miR-30a through other cell signaling pathways. In this positive feedback mechanism AR is then upregulated through miR-30a. Overexpression of miR-30a inhibited cell proliferation, whereas inhibition of miR-30a expression by specific antisense oligonucleotides, increased cell growth. Previously, androgen-induced AR activating signal was demonstrated to inhibit cell proliferation in ER - , PR - and AR + MDA-MB-453 breast cancer cells, but AR activating signal downregulated the expression of miR-30a, relieving the inhibition of MDA-MB-453 cell growth. Therefore, in MDA-MB-453 breast cancer cells, miR-30a has two different functions regarding cell growth: Inhibition of cell proliferation through a positive feedback signaling pathway; and the relative promotion of cell proliferation through downregulation of miR-30a. Thus, the association between AR activating signal and microRNAs is complex, and microRNAs may possess different functions due to different signaling pathways. Although the results of the present study were obtained in one cell line, they contribute to subsequent studies on ER - , PR - and AR + breast cancer.

The 40Ar/39Ar dating technique applied to planetary sciences

NASA Astrophysics Data System (ADS)

Jourdan, F.

2012-12-01

The 40Ar/39Ar technique is a powerful geochronological method that can help to unravel the evolution of the solar system. The 40Ar/39Ar system can not only record the timing of volcanic and metamorphic processes on asteroids and planets, it finds domain of predilection in dating impact events throughout the solar system. However, the 40Ar/39Ar method is a robust analytical technique if, and only if, the events to be dated are well understood and data are not over interpreted. Yet, too many 'ages' reported in the literature are still based on over-interpretation of perturbed age spectra which tends to blur the big picture. This presentation is centred on the most recent applications of the 40Ar/39Ar technique applied to planetary material and through several examples, will attempt to demonstrate the benefit of focusing on statistically robust data. For example, 40Ar/39Ar dating of volcanic events on the Moon suggests that volcanism was mostly concentrated between ca. 3.8 and 3.1 Ga but statistical filtering of the data allow identifying a few well-defined eruptive events. The study of lunar volcanism would also benefit from dating of volcanic spherules. Rigorous filtering of the 40Ar/39Ar age database of lunar melt breccias yielded concordant and ages with high precision for two major basins (i.e. Imbrium & Serenitatis) of the Moon. 40Ar/39Ar dating of lunar impact spherules recovered from four different sites and with high- and low-K compositions shows an increase of ages younger than 400 Ma suggesting a recent increase in the impact flux. The impact history of the LL parent body (bodies?) has yet to be well constrained but may mimic the LHB observed on the Moon, which would indicate that the LL parent body was quite large. 40Ar/39Ar dating (in progress) of grains from the asteroid Itokawa recovered by the japanese Hayabusa mission have the potential to constrain the formation history and exposure age of Itokawa and will allow us to compare the results with the impact history recorded by LL chondrites. Basaltic meteorites (HEDs) show a 40Ar/39Ar age range between 4.1 and 3.4 Ga, suggesting a diffuse LHB event; however, the spread of apparent ages may be a data interpretation artefact, as new solid plateau age data suggest that the bombardment by large asteroids might have occurred over a briefer period between 3.5 and 3.8 Ga.

Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells.

PubMed

Gong, J; Zhu, J; Goodman, O B; Pestell, R G; Schlegel, P N; Nanus, D M; Shen, R

2006-03-30

Androgen receptor signaling in prostate cancer cells is augmented by the androgen receptor (AR) coactivator p300, which transactivates and acetylates the AR in the presence of dihydrotestosterone (DHT). As prostate cancer (PC) cells progress to androgen independence, AR signaling remains intact, indicating that other factors stimulate AR activities in the absence of androgen. We previously reported that neuropeptide growth factors could transactivate the AR in the presence of very low concentrations of DHT. Here, we examine the involvement of p300 in neuropeptide activation of AR signaling. Transfection of increasing concentrations of p300 in the presence of bombesin into PC-3 cells resulted in a linear increase in AR transactivation, suggesting that p300 acts as a coactivator in neuropeptide-mediated AR transactivation. P300 is endowed with histone acetyltransferase (HAT) activity. Therefore, we examine the effect of bombesin on p300 HAT activity. At 4 h after the addition of bombesin, p300 HAT activity increased 2.0-fold (P<0.01). Incubation with neutral endopeptidase, which degrades bombesin, or bombesin receptor antagonists blocked bombesin-induced p300 HAT activity. To explore the potential signaling pathways involved in bombesin-induced p300 HAT activity, we examined Src and PKCdelta pathways that mediate bombesin signaling. Inhibitors of Src kinase activity or Src kinase siRNA blocked bombesin-induced p300 HAT activity, whereas PKCdelta inhibitors or PKCdelta siRNA significantly increased bombesin-induced p300 HAT activity suggesting that Src kinase and PKCdelta kinase are involved in the regulation of p300 HAT activity. As AR is acetylated in the presence of 100 nM DHT, we next examined whether bombesin-induced p300 HAT activity would result in enhanced AR acetylation. Bombesin-induced AR acetylation at the same motif KLKK observed in DHT-induced acetylation. Elimination of p300 using p300 siRNA reduced AR acetylation, demonstrating that AR acetylation was mediated by p300. AR acetylation results in AR transactivation and the expression of the AR-regulated gene prostate-specific antigen (PSA). Therefore, we examined bombesin-induced AR transactivation and PSA expression in the presence and absence of p300 siRNA and found inhibition of p300 expression reduced bombesin-induced AR transactivation and PSA expression. Together these results demonstrate that bombesin, via Src and PKCdelta signaling pathways, activates p300 HAT activity which leads to enhanced acetylation of AR resulting in increased expression of AR-regulated genes.

Legacy K/Ar and 40Ar/39Ar geochronologic data from the Alaska-Aleutian Range batholith of south-central Alaska

USGS Publications Warehouse

Koeneman, Lisa L.; Wilson, Frederic H.

2018-04-06

Sample descriptions and analytical data for more than 200 K/Ar and 40Ar/39Ar analyses from rocks of the Alaska-Aleutian Range batholith of south-central Alaska are reported here. Samples were collected over a period of 20 years by Bruce R. Reed and Marvin A. Lanphere (both U.S. Geological Survey) as part of their studies of the batholith.

Cross sections of the 36Ar(d,α)34mCl, 40Ar(d,α)38Cl, and 40Ar(d,p)41Ar nuclear reactions below 8.4 MeV.

PubMed

Engle, J W; Severin, G W; Barnhart, T E; Knutson, L D; Nickles, R J

2012-02-01

We have measured the cross section for production of the medically interesting isotope (34m)Cl, along with (38)Cl and (41)Ar, using deuteron bombardments of (36)Ar and (40)Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas. Copyright © 2011 Elsevier Ltd. All rights reserved.

Armenian Astronomical Society Annual Activities in 2014

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.

2015-07-01

A report is given on the achievements of the Armenian astronomy during the last year and on the present activities of the Armenian Astronomical Society (ArAS). ArAS membership, ArAS electronic newsletters (ArASNews), ArAS webpage, annual meetings, Annual Prize for Young Astronomers (Yervant Terzian Prize) and other awards, international relations, presence in international organizations, summer schools, astronomical Olympiads and other events, matters related to astronomical education, astronomical heritage, astronomy outreach and ArAS further projects are discussed. The present meeting, BAO Science Camp, ArAS School lectures are among 2014 events as well.

AR4VI: AR as an Accessibility Tool for People with Visual Impairments

PubMed Central

Coughlan, James M.; Miele, Joshua

2017-01-01

Although AR technology has been largely dominated by visual media, a number of AR tools using both visual and auditory feedback have been developed specifically to assist people with low vision or blindness – an application domain that we term Augmented Reality for Visual Impairment (AR4VI). We describe two AR4VI tools developed at Smith-Kettlewell, as well as a number of pre-existing examples. We emphasize that AR4VI is a powerful tool with the potential to remove or significantly reduce a range of accessibility barriers. Rather than being restricted to use by people with visual impairments, AR4VI is a compelling universal design approach offering benefits for mainstream applications as well. PMID:29303163

AR4VI: AR as an Accessibility Tool for People with Visual Impairments.

PubMed

Coughlan, James M; Miele, Joshua

2017-10-01

Although AR technology has been largely dominated by visual media, a number of AR tools using both visual and auditory feedback have been developed specifically to assist people with low vision or blindness - an application domain that we term Augmented Reality for Visual Impairment (AR4VI). We describe two AR4VI tools developed at Smith-Kettlewell, as well as a number of pre-existing examples. We emphasize that AR4VI is a powerful tool with the potential to remove or significantly reduce a range of accessibility barriers. Rather than being restricted to use by people with visual impairments, AR4VI is a compelling universal design approach offering benefits for mainstream applications as well.

A pulsed plasma jet with the various Ar/N2 mixtures

NASA Astrophysics Data System (ADS)

Barkhordari, A.; Ganjovi, A.; Mirzaei, I.; Falahat, A.; Rostami Ravari, M. N.

2017-12-01

In this paper, using the Optical Emission Spectroscopy technique, the physical properties of a fabricated pulsed DBD plasma jet are studied. Ar/N2 gaseous mixture is taken as operational gas, and Ar contribution in Ar/N2 mixture is varied from 75 to 95%. Through the optical emission spectra analysis of the pulsed DBD plasma jet, the rotational, vibrational and excitation temperatures and density of electrons in plasma medium of the pulsed plasma jet are obtained. It is seen that, at the wavelength of 750.38 nm, the radiation intensity from the Ar 4p → 4 s transition increases at the higher Ar contributions in Ar/N2 mixture. It is found that, for 95% of Ar presence in the mixture, the emission intensities from argon and molecular nitrogen are higher, and the emission line intensities will increase nonlinearly. In addition, it is observed that the quenching of Ar* by N2 results in the higher intensities of N2 excited molecules. Moreover, at the higher percentages of Ar in Ar/N2 mixture, while all the plasma temperatures are increased, the plasma electron density is reduced.

Optical characteristics of a RF DBD plasma jet in various {Ar}/ {O}_{2}Ar/O2 mixtures

NASA Astrophysics Data System (ADS)

Falahat, A.; Ganjovi, A.; Taraz, M.; Ravari, M. N. Rostami; Shahedi, A.

2018-02-01

In this paper, using the optical emission spectroscopy (OES) technique, the optical characteristics of a radiofrequency (RF) plasma jet are examined. The Ar/O2 mixture is taken as the operational gas and, the Ar percentage in the Ar/O2 mixture is varied from 70% to 95%. Using the optical emission spectrum analysis of the RF plasma jet, the excitation temperature is determined based on the Boltzmann plot method. The electron density in the plasma medium of the RF plasma jet is obtained by the Stark broadening of the hydrogen Balmer H_{β }. It is mostly seen that, the radiation intensity of Ar 4p→ 4s transitions at higher argon contributions in Ar/O2 mixture is higher. It is found that, at higher Ar percentages, the emission intensities from atomic oxygen (O) are higher and, the line intensities from the argon atoms and ions including O atoms linearly increase. It is observed that the quenching of Ar^{*} with O2 results in higher O species with respect to O2 molecules. In addition, at higher percentages of Ar in the Ar/O2 mixture, while the excitation temperature is decreased, the electron density is increased.

40Ar/39Ar technique of KAr dating: a comparison with the conventional technique

USGS Publications Warehouse

Brent, Dalrymple G.; Lanphere, M.A.

1971-01-01

K-Ar ages have been determined by the 40Ar/39Ar total fusion technique on 19 terrestrial samples whose conventional K-Ar ages range from 3.4 my to nearly 1700 my. Sample materials included biotite, muscovite, sanidine, adularia, plagioclase, hornblende, actinolite, alunite, dacite, and basalt. For 18 samples there are no significant differences at the 95% confidence level between the KAr ages obtained by these two techniques; for one sample the difference is 4.3% and is statistically significant. For the neutron doses used in these experiments (???4 ?? 1018 nvt) it appears that corrections for interfering Ca- and K-derived Ar isotopes can be made without significant loss of precision for samples with K/Ca > 1 as young as about 5 ?? 105 yr, and for samples with K/Ca < 1 as young as about 107 yr. For younger samples the combination of large atmospheric Ar corrections and large corrections for Ca- and K-derived Ar may make the precision of the 40Ar/39Ar technique less than that of the conventional technique unless the irradiation parameters are adjusted to minimize these corrections. ?? 1971.

KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

PubMed Central

Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

2015-01-01

Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants

PubMed Central

Sun, Feng; Indran, Inthrani R.; Zhang, Zhi Wei; Tan, M.H.Eileen; Li, Yu; Lim, Z.L.Ryan; Hua, Rui; Yang, Chong; Soon, Fen-Fen; Li, Jun; Xu, H.Eric; Cheung, Edwin; Yong, Eu-Leong

2015-01-01

Persistent androgen receptor (AR) signaling is the key driving force behind progression and development of castration-resistant prostate cancer (CRPC). In many patients, AR COOH-terminal truncated splice variants (ARvs) play a critical role in contributing to the resistance against androgen depletion therapy. Unfortunately, clinically used antiandrogens like bicalutamide (BIC) and enzalutamide (MDV), which target the ligand binding domain, have failed to suppress these AR variants. Here, we report for the first time that a natural prenylflavonoid, icaritin (ICT), can co-target both persistent AR and ARvs. ICT was found to inhibit transcription of key AR-regulated genes, such as KLK3 [prostate-specific antigen (PSA)] and ARvs-regulated genes, such as UBE2C and induce apoptosis in AR-positive prostate cancer (PC) cells. Mechanistically, ICT promoted the degradation of both AR and ARvs by binding to arylhydrocarbon-receptor (AhR) to mediate ubiquitin-proteasomal degradation. Therefore, ICT impaired AR transactivation in PC cells. Knockdown of AhR gene restored AR stability and partially prevented ICT-induced growth suppression. In clinically relevant murine models orthotopically implanted with androgen-sensitive and CRPC cells, ICT was able to target AR and ARvs, to inhibit AR signaling and tumor growth with no apparent toxicity. Our results provide a mechanistic framework for the development of ICT, as a novel lead compound for AR-positive PC therapeutics, especially for those bearing AR splice variants. PMID:25908644

Characteristics of southern California atmospheric rivers

NASA Astrophysics Data System (ADS)

Harris, Sarah M.; Carvalho, Leila M. V.

2018-05-01

Atmospheric rivers (ARs) are channels of high water vapor flux that transport moisture from low to higher latitudes on synoptic timescales. In areas of topographical variability, ARs may lead to high-intensity precipitation due to orographic forcing. ARs landfalling along North America's west coast are linked to extreme events including those leading to flooding and landslides. In southern California (SCA), proper AR forecasting is important for regional water resources as well as hazard mitigation and as the area's annual precipitation totals occur from relatively few storms per season, any changes to storm frequency and/or intensity may have dramatic consequences. Yet, as most regional AR studies focus on the Pacific Northwest, there is little information about SCA ARs. We develop an algorithm to identify ARs landfalling on North America's west coast between 1979 and 2013 within total precipitable water reanalysis fields. ARs are then categorized according to landfall region. To determine and differentiate the characteristics and spatial distributions of ARs affecting these areas, we examine lag composites of various atmospheric variables for each landfall region. SCA ARs differ from ARs landfalling farther north in the days prior to landfall with the position and amplitude of a trough offshore from the Asian continent and ridge over Alaska, as well as the displacement and eastward extension of the jet core that potentially guides AR moisture southwards. The relationships between AR landfalls and the El Niño/Southern Oscillation (ENSO), the Madden-Julian Oscillation (MJO), and the Pacific/North American Teleconnection Pattern (PNA) are also investigated.

Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy

PubMed Central

Pang, Yilin; Mai, Zihao; Wang, Bin; Wang, Lu; Wu, Liping; Wang, Xiaoping; Chen, Tongsheng

2017-01-01

Poor water-solubility of artesunate (ARS) hampers its clinical application. We here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen species (ROS) and peroxynitrite (ONOO─) generations. Although nGO-PEG with near-infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO─ generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO─ scavenger) instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation, demonstrating that ONOO─ instead of ROS dominated the synergistic chemo-photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation resulted in a complete tumor cure within 15 days earlier than other treatment groups, and did not induce apparent histological lesion for the mice treated with nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy. PMID:29212190

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Binding of bisphenol A, bisphenol AF, and bisphenol S on the androgen receptor: Coregulator recruitment and stimulation of potential interaction sites.

PubMed

Perera, Lalith; Li, Yin; Coons, Laurel A; Houtman, Rene; van Beuningen, Rinie; Goodwin, Bonnie; Auerbach, Scott S; Teng, Christina T

2017-10-01

Bisphenol A (BPA), bisphenol AF (BPAF), and bisphenol S (BPS) are well known endocrine disruptors. Previous in vitro studies showed that these compounds antagonize androgen receptor (AR) transcriptional activity; however, the mechanisms of action are unclear. In the present study, we investigated interactions of coregulator peptides with BPA, BPAF, or BPS at the AR complexes using Micro Array for Real-time Coregulator Nuclear Receptor Interaction (MARCoNI) assays and assessed the binding of these compounds on AR by molecular dynamics (MD) simulations. The set of coregulator peptides that are recruited by BPA-bound AR, either positively/or negatively, are different from those recruited by the agonist R1881-bound AR. Therefore, the data indicates that BPA shows no similarities to R1881 and suggests that it may recruit other coregulators to the AR complex. BPAF-bound AR recruits about 70-80% of the same coregulator peptides as BPA-bound AR. Meanwhile, BPS-bound AR interacts with only few peptides compared to BPA or BPAF-bound AR. MD results show that multiple binding sites with varying binding affinities are available on AR for BPA, BPAF, and BPS, indicating the availability of modified binding surfaces on AR for coregulator interactions. These findings help explain some of the distinct AR-related toxicities observed with bisphenol chemicals and raise concern for the use of substitutes for BPA in commercial products. Published by Elsevier Ltd.

The 40Ar/39Ar and K/Ar dating of lavas from the Hilo 1-km core hole, Hawaii Scientific Drilling Project

USGS Publications Warehouse

Sharp, W.D.; Turrin, B.D.; Renne, P.R.; Lanphere, M.A.

1996-01-01

Mauna Kea lava flows cored in the HilIo hole range in age from <200 ka to about 400 ka based on 40Ar/39Ar incremental heating and K-Ar analyses of 16 groundmass samples and one coexisting plagioclase. The lavas, all subaerially deposited, include a lower section consisting only of tholeiitic basalts and an upper section of interbedded alkalic, transitional tholeiitic, and tholeiitic basalts. The lower section has yielded predominantly complex, discordant 40Ar/39Ar age spectra that result from mobility of 40Ar and perhaps K, the presence of excess 40Ar, and redistribution of 39Ar by recoil. Comparison of K-Ar ages with 40Ar/39Ar integrated ages indicates that some of these samples have also lost 39Ar. Nevertheless, two plateau ages of 391 ?? 40 and 400 ?? 26 ka from deep in the hole, combined with data from the upper section, show that the tholeiitic section accumulated at an average rate of about 7 to 8 m/kyr and has an mean recurrence interval of 0.5 kyr/flow unit. Samples from the upper section yield relatively precise 40Ar/39Ar plateau and isotope correlation ages of 326 ?? 23, 241 ?? 5, 232 ?? 4, and 199 ?? 9 ka for depths of -415.7 m to -299.2 m. Within their uncertainty, these ages define a linear relationship with depth, with an average accumulation rate of 0.9 m/kyr and an average recurrence interval of 4.8 kyr/flow unit. The top of the Mauna Kea sequence at -280 m must be older than the plateau age of 132 ?? 32 ka, obtained for the basal Mauna Loa flow in the corehole. The upward decrease in lava accumulation rate is a consequence of the decreasing magma supply available to Mauna Kea as it rode the Pacific plate away from its magma source, the Hawaiian mantle plume. The age-depth relation in the core hole may be used to test and refine models that relate the growth of Mauna Kea to the thermal and compositional structure of the mantle plume.

Adult body size and physical activity in relation to risk of breast cancer according to tumor androgen receptor status.

PubMed

Zhang, Xuehong; Eliassen, A Heather; Tamimi, Rulla M; Hazra, Aditi; Beck, Andrew H; Brown, Myles; Collins, Laura C; Rosner, Bernard; Hankinson, Susan E

2015-06-01

Obesity and physical activity have been hypothesized to affect breast cancer risk partly via the androgen signaling pathway. We conducted the first study to evaluate these associations by tumor androgen receptor (AR) status. Height, weight, and physical activity were assessed using questionnaires in the Nurses' Health Study. AR, estrogen receptor (ER), and progesterone receptor (PR) status were determined using immunohistochemistry on tumor tissue and medical/pathology reports. A total of 1,701 AR(+) and 497 AR(-) cases were documented during 26 years of follow-up of 103,577 women. After adjusting for ER/PR status and other risk factors, the relative risks (RR) and 95% confidence intervals (95% CI) for every 5 kg/m(2) increase in body mass index (BMI) were 1.07 (1.01-1.13) for AR(+) and 1.16 (1.05-1.29) for AR(-) tumors (P-heterogeneity = 0.17). The RRs (95% CIs) per 5 hours of brisk walking/week were 0.87 (0.73-1.04) for AR(+) and 0.67 (0.45-0.99) for AR(-) tumors (P-heterogeneity = 0.22). Further, BMI, but not physical activity, associations differed significantly across ER/PR/AR subtypes (P-heterogeneity = 0.04 and 0.63, respectively). The RRs (95% CIs) for 5 kg/m(2) increase in BMI were 1.23 (1.04-1.45) for ER(+)PR(+)AR(-), 1.19 (1.01-1.39) for ER(-)PR(-)AR(-), 1.15 (1.08-1.23) for ER(+)PR(+)AR(+), and 0.88 (0.75-1.03) for ER(+)PR(-)AR(+) tumors. Higher BMI was associated with an increased risk of both AR(+) and AR(-) breast tumors in postmenopausal women, whereas physical activity, including brisk walking, was associated with a reduced risk of both subtypes. In addition, a significant positive association was observed between higher BMI and ER(-)PR(-)AR(-) tumors. The similar associations observed by AR status suggest that mechanisms other than androgen signaling underlie these two breast cancer risk factors. ©2015 American Association for Cancer Research.

Ar-Ar and I-Xe Ages and the Thermal History of IAB Meteorites

NASA Technical Reports Server (NTRS)

Bogard, Donald D.; Garrison, Daniel H.; Takeda, Hiroshi

2005-01-01

Studies of several samples of the large Caddo County IAB iron meteorite reveal andesitic material, enriched in Si, Na, Al and Ca, which is essentially unique among meteorites. This material is believed to have formed from a chondritic source by partial melting and to have further segregated by grain coarsening. Such an origin implies extended metamorphism of the IAB parent body. New Ar-39- Ar-40 ages for silicate from three different Caddo samples are consistent with a common age of 4.50-4.51 Gyr ago. Less well defined Ar-Ar degassing ages for inclusions from two other IABs, EET8333 and Udei Station, are approx.4.32 Gyr, whereas the age for Campo del Cielo varies considerably over approx.3.23-4.56 Gyr. New I-129-Xe-129 ages for Caddo County and EET8333 are 4557.9+/-0.1 Myr and 4557-4560 Myr, respectively, relative to an age of 4562.3 Myr for Shallowater. Considering all reported Ar-Ar degassing ages for IABs and related winonaites, the range is approx.4.32-4.53 Gyr, but several IABs give similar Ar ages of 4.50-4.52 Gyr. We interpret these older Ar ages to represent cooling after the time of last significant metamorphism on the parent body, and the younger ages to represent later 40Ar diffusion loss. The older Ar-Ar ages for IABs are similar to Sm-Nd and Rb-Sr isochron ages reported in the literature for Caddo County. Considering the possibility that IAB parent body formation was followed by impact disruption, reassembly, and metamorphism (e.g., Benedix et al. 2000), the Ar-Ar ages and IAB cooling rates deduced from Ni concentration profiles in IAB metal (Herpfer et al., 1994) are consistent if the time of the post-assembly metamorphism was as late as approx.4.53 Gyr ago. However, I-Xe ages reported for some IABs define much older ages of approx.4558-4566 Myr, which cannot easily be reconciled with the much younger Ar-Ar and Sm-Nd ages. An explanation for the difference in radiometric ages of IABs may reside in combinations of the following: a) I-Xe ages have very high closure temperatures and were not reset during metamorphism approx.4.53 Gyr ago; b) a bias exists in the 40K decay constants which makes these Ar-Ar ages approx.30 Myr too young; c) the reported Sm-Nd and Rb-Sr ages for Caddo are in error by amounts equal to or exceeding their reported 2-sigma uncertainties; and d) about 30 Myr after the initial heating that produced differentiation of Caddo silicate and mixing of silicate and metal, a mild metamorphism of the IAB parent body reset the Ar-Ar ages.

High Spatial Resolution 40Ar/39Ar Geochronology of Lunar Impact Melt Rocks

NASA Astrophysics Data System (ADS)

Mercer, Cameron Mark

Impact cratering has played a key role in the evolution of the solid surfaces of Solar System bodies. While much of Earth’s impact record has been erased, its Moon preserves an extensive history of bombardment. Quantifying the timing of lunar impact events is crucial to understanding how impacts have shaped the evolution of early Earth, and provides the basis for estimating the ages of other cratered surfaces in the Solar System. Many lunar impact melt rocks are complex mixtures of glassy and crystalline “melt” materials and inherited clasts of pre-impact minerals and rocks. If analyzed in bulk, these samples can yield complicated incremental release 40Ar/39Ar spectra, making it challenging to uniquely interpret impact ages. Here, I have used a combination of high-spatial resolution 40Ar/39Ar geochronology and thermal-kinetic modeling to gain new insights into the impact histories recorded by such lunar samples. To compare my data to those of previous studies, I developed a software tool to account for differences in the decay, isotopic, and monitor age parameters used for different published 40Ar/39Ar datasets. Using an ultraviolet laser ablation microprobe (UVLAMP) system I selectively dated melt and clast components of impact melt rocks collected during the Apollo 16 and 17 missions. UVLAMP 40Ar/39Ar data for samples 77135, 60315, 61015, and 63355 show evidence of open-system behavior, and provide new insights into how to interpret some complexities of published incremental heating 40Ar/39Ar spectra. Samples 77115, 63525, 63549, and 65015 have relatively simple thermal histories, and UVLAMP 40Ar/39Ar data for the melt components of these rocks indicate the timing of impact events—spanning hundreds of millions of years—that influenced the Apollo 16 and 17 sites. My modeling and UVLAMP 40Ar/39Ar data for sample 73217 indicate that some impact melt rocks can quantitatively retain evidence for multiple melt-producing impact events, and imply that such polygenetic rocks should be regarded as high-value sampling opportunities during future exploration missions to cratered planetary surfaces. Collectively, my results complement previous incremental heating 40Ar/39Ar studies, and support interpretations that the Moon experienced a prolonged period of heavy bombardment early in its history.

Ar-39-Ar-40 Evidence for Early Impact Events on the LL Parent Body

NASA Technical Reports Server (NTRS)

Dixon, E. T.; Bogard, D. D.; Garrison, D. H.; Rubin, A. E.

2006-01-01

We determined Ar-39-Ar-40 ages of eight LL chondrites, and one igneous inclusion from an LL chondrite, with the object of understanding the thermal history of the LL-chondrite parent body. The meteorites in this study have a range of petrographic types from LL3.3 to LL6, and shock stages from S1 to S4. These meteorites reveal a range of K-Ar ages from 23.66 to 24.50 Ga, and peak ages from 23.74 to 24.55 Ga. Significantly, three of the eight chondrites (LL4, 5, 6) have K-Ar ages of -4.27 Ga. One of these (MIL99301) preserves an Ar-39-Ar-40 age of 4.23 +/- 0.03 Ga from low-temperature extractions, and an older age of 4.52 +/- 0.08 Ga from the highest temperature extractions. In addition, an igneous-textured impact melt DOM85505,22 has a peak Ar-39-Ar-40 age of >= 4.27 Ga. We interpret these results as evidence for impact events that occurred at about 4.27 Ga on the LL parent body that produced local impact melts, reset the Ar-39-Ar-40 ages of some meteorites, and exhumed (or interred) others, resulting in a range of cooling ages. The somewhat younger peak age of 3.74 Ga from GR095658 (LL3.3) suggests an additional impact event close to timing of impact-reset ages of some other ordinary chondrites between 3.6-3.8 Ga. The results from MIL99301 suggest that some apparently unshocked (Sl) chondrites may have substantially reset Ar-39-Ar-40 ages. A previous petrographic investigation of MIL99301 suggested that reheating to temperatures less than or equal to type 4 petrographic conditions (600C) caused fractures in olivine to anneal, resulting in a low apparent shock stage of S1 (unshocked). The Ar-39-Ar-40 age spectrum of MIL99301 is consistent with this interpretation. Older ages from high-T extractions may date an earlier impact event at 4.52 +/- 0.08 Ga, whereas younger ages from lower-T extractions date a later impact event at 4.23 Ar-39-Ar-40 0.03 Ga that may have caused annealing of feldspar and olivine

Landfalling Atmospheric Rivers in California—Historical and Future Impacts

NASA Astrophysics Data System (ADS)

Dettinger, M. D.; Ralph, F. M.

2014-12-01

During the past decade, a wide range of insights about the character and causes of extreme orographic precipitation in California has emerged, based on our growing understanding of the presence, mechanisms and impacts of "atmospheric rivers" (ARs) in the extratropical atmosphere. When an AR reaches and encounters the Coastal Ranges and Sierra Nevada of California, the resulting orographically driven storms are key players in many important weather, hydrologic and ecological processes in the State, including floods and floodplain inundations, droughts, groundwater recharge, and surface-water resources (see table). The intensities, storm totals, geographical distributions and impacts of AR storms in California are determined by many factors, including among the most straightforward: The numbers of ARs making landfall each year The amounts of vapor being transported by the ARs The direction of vapor transport by the AR relative to perpendiculars to the mountain ranges (for maximum uplift) The duration of AR passage overhead of a given location The temperature of an AR as a determinant of snowline altitudes The stability of the atmosphere within which the AR is embedded The closeness of the air in the AR to saturation (how much uplift is needed to drive intense precipitation) ARs are present in weather forecast models as well as in the long-range climate models used to project future climate changes in response to increasing greenhouse-gas concentrations in the atmosphere. Research into the future of ARs over California was first reported in the literature in 2011 (based on IPCC AR4 climate models) and is being extended now (to IPCC AR5 models) to assess projected changes in the full range of factors listed above with the aim of predicting how climate change will affect these important storms and their impacts in coming decades.

Galbanic acid decreases androgen receptor abundance and signaling and induces G1 arrest in prostate cancer cells

PubMed Central

Zhang, Yong; Kim, Kwan-Hyun; Zhang, Wei; Guo, Yinglu; Kim, Sung-Hoon; Lü, Junxuan

2011-01-01

Androgen receptor (AR) signaling is crucial for the genesis and progression of prostate cancer (PCa). We compared the growth responses of AR(+) LNCaP and LNCaP C4-2 vs. AR(−) DU145 and PC-3 PCa cell lines to galbanic acid (GBA) isolated from the resin of medicinal herb Ferula assafoetida and assessed their connection to AR signaling and cell cycle regulatory pathways. Our results showed that GBA preferentially suppressed AR(+) PCa cell growth than AR(−) PCa cells. GBA induced a caspase-mediated apoptosis that was attenuated by a general caspase inhibitor. Subapoptotic GBA down-regulated AR protein in LNCaP cells primarily through promoting its proteasomal degradation, and inhibited AR-dependent transcription without affecting AR nuclear translocation. Whereas docking simulations predicted binding of GBA to the AR ligand binding domain with similarities and differences with the AR antagonist drug bicalutamide, LNCaP cell culture assays did not detect agonist activity of GBA. GBA and bicalutamide exerted greater than additive inhibitory effect on cell growth when used together. Subapoptotic GBA induced G1 arrest associated with an inhibition of cyclin/CDK4/6 pathway, especially cyclin D1 without the causal involvement of CDK inhibitory proteins P21Cip1 and P27Kip1. In summary, the novelty of GBA as an anti-AR compound resides in the distinction between GBA and bicalutamide with respect to AR protein turnover and a lack of agonist effect. Our observations of anti-AR and cell cycle arrest actions plus the anti-angiogenesis effect reported elsewhere suggest GBA as a multi-targeting drug candidate for the prevention and therapy of PCa. PMID:21328348

Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

PubMed Central

Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

2017-01-01

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor

PubMed Central

Coleman, Daniel J.; Van Hook, Kathryn; King, Carly J.; Schwartzman, Jacob; Lisac, Robert; Urrutia, Joshua; Sehrawat, Archana; Woodward, Josha; Wang, Nicholas J.; Gulati, Roman; Thomas, George V.; Beer, Tomasz M.; Gleave, Martin; Korkola, James E.; Gao, Lina; Heiser, Laura M.; Alumkal, Joshi J.

2016-01-01

Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) – the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. PMID:27276681

Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer.

PubMed

Kashiwagi, Eiji; Ide, Hiroki; Inoue, Satoshi; Kawahara, Takashi; Zheng, Yichun; Reis, Leonardo O; Baras, Alexander S; Miyamoto, Hiroshi

2016-08-02

Cisplatin (CDDP)-based combination chemotherapy remains the mainstream treatment for advanced bladder cancer. However, its efficacy is often limited due to the development of resistance for which underlying mechanisms are poorly understood. Meanwhile, emerging evidence has indicated the involvement of androgen-mediated androgen receptor (AR) signals in bladder cancer progression. In this study, we aimed to investigate whether AR signals have an impact on sensitivity to CDDP in bladder cancer cells. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous AR and AR-negative 647V/5637 cells stably expressing AR were significantly more resistant to CDDP treatment at its pharmacological concentrations, compared with UMUC3-AR-shRNA and 647V-vector/5637-vector control cells, respectively. A synthetic androgen R1881 significantly reduced CDDP sensitivity in UMUC3, 647V-AR, or 5637-AR cells, and the addition of an anti-androgen hydroxyflutamide inhibited the effect of R1881. In these AR-positive cells, R1881 treatment also induced the expression levels of NF-κB, which is known to involve CDDP resistance, and its phosphorylated form, as well as nuclear translocation of NF-κB. In CDDP-resistant bladder cancer sublines established following long-term culture with CDDP, the expression levels of AR as well as NF-κB and phospho-NF-κB were considerably elevated, compared with respective control sublines. In bladder cancer specimens, there was a strong trend to correlate between AR positivity and chemoresistance. These results suggest that AR activation correlates with CDDP resistance presumably via modulating NF-κB activity in bladder cancer cells. Targeting AR during chemotherapy may thus be a useful strategy to overcome CDDP resistance in patients with AR-positive bladder cancer.

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells

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

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H.; Morton, Derrick J.

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, wemore » examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. - Highlights: • ID4 expression induces AR expression in PC3 cells, which generally lack AR. • ID4 expression increased apoptosis and decreased cell proliferation and invasion. • Overexpression of ID4 reduces tumor growth of subcutaneous xenografts in vivo. • ID4 induces p21 and FKBP51 expression- co-factors of AR tumor suppressor activity.« less

Effects of a preemptive alveolar recruitment strategy on arterial oxygenation during one-lung ventilation with different tidal volumes in patients with normal pulmonary function test.

PubMed

Jung, Jong Dal; Kim, Sang Hun; Yu, Byung Sik; Kim, Hye Ji

2014-08-01

Hypoxemia during one-lung ventilation (OLV) remains a major concern. The present study compared the effect of alveolar recruitment strategy (ARS) on arterial oxygenation during OLV at varying tidal volumes (Vt) with or without positive end-expiratory pressure (PEEP). In total, 120 patients undergoing wedge resection by video assisted thoracostomy were randomized into four groups comprising 30 patients each: those administered a 10 ml/kg tidal volume with or without preemptive ARS (Group H and Group H-ARS, respectively) and those administered a 6 ml/kg tidal volume and a 8 cmH2O PEEP with or without preemptive ARS (Group L and Group L-ARS, respectively). ARS was performed using pressure-controlled ventilation with a 40 cmH2O plateau airway pressure and a 15 cmH2O PEEP for at least 10 breaths until OLV began. Preemptive ARS significantly improved the PaO2/FiO2 ratio compared to the groups that did not receive ARS (P < 0.05). The H-ARS group showed a highest PaO2/FiO2 ratio during OLV, the L-ARS and H groups showed similarly improved arterial oxygenation, which was significantly higher than in group L (P < 0.05). The plateau airway pressure in group H-ARS was significantly higher than in group L-ARS (P < 0.05). Preemptive ARS can improve arterial oxygenation during OLV. Furthermore, a 6 ml/kg tidal volume combined with 8 cmH2O PEEP after preemptive ARS may reduce the risk of pulmonary injury caused by high tidal volume during one-lung ventilation in patients with normal pulmonary function.

Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor.

PubMed

Fan, WuQiang; Yanase, Toshihiko; Nishi, Yoshihiro; Chiba, Seiichi; Okabe, Taijiro; Nomura, Masatoshi; Yoshimatsu, Hironobu; Kato, Shigeaki; Takayanagi, Ryoichi; Nawata, Hajime

2008-12-01

Hypogonadism is associated with increased fat mass and dysregulation of metabolic homeostasis in men. Our previous study revealed that androgen receptor (AR)-null male mice (ARL-/Y) develop late-onset obesity and are leptin-resistant. The present study evaluated how hypothalamic AR contributes to central leptin-signal transducer and activator of transcription 3 (STAT3) signaling. We evaluated leptin action in wild-type and ARL-/Y mice, the anatomic co-relationship between AR and leptin signaling in the hypothalamus, and the effects of AR on leptin-mediated STAT3 transactivation and nuclear translocation. AR deletion in male mice results in a weaker leptin-induced suppression of food intake and body weight drop even before the onset of overt obesity. In wild-type male but not female mice, AR was highly expressed in various hypothalamic nuclei that also expressed the long-form leptin receptor (OBRB) and co-resided with OBRB directly in the arcuate neurons. In vitro, AR significantly enhanced STAT3-mediated transcription of leptin target genes including POMC and SOCS3. This effect relied on the AR N-terminal activation function-1 (AF-1) domain and was specific to AR in that none of the other sex steroid hormone receptors tested showed similar effects. AR enhanced the low concentrations of leptin-induced STAT3 nuclear translocation in vitro, and ARL-/Y mice receiving leptin had impaired STAT3 nuclear localization in the arcuate neurons. These findings indicate that AR in the hypothalamus functions as a regulator of central leptin-OBRB-STAT3 signaling and has a physiological role in energy homeostasis and metabolic regulation in male mice.

Army Family Policies and Practices: A Summary of Regulations, Letters, Pamphlets, and Circulars That Impact on Army Families

DTIC Science & Technology

1990-05-01

AR 60-10 Army and Air Force Exchange Service (AAFES) General Policies.. ................. . . . 12 AR 60-2 0 Army and Air Force Exchange Service (AAFES...Initial Active Duty, Initial Active Duty for Training, and Reserve Forces Duty . . . . . . ........... 29 AR 601-27 Military Entrance Processing...AR 608-20 Voting by Personnel of the Armed Forces . . . . .... 35 AR 608-25 Retirement Services Program . ...... 36 AR 608-61 Application for

Prostaglandins, steroids and reception (an attempt to model the structure of the active centers of adrenoreception).

PubMed

Podymov, V K; Piruzyan, L A; Gladkikh, S P; Kats, M M; Nizhnii, S V

1980-01-01

On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc.

Differences in the cancer burden among foreign-born and US-born Arab Americans living in metropolitan Detroit.

PubMed

Khan, Fatima; Ruterbusch, Julie J; Gomez, Scarlett L; Schwartz, Kendra

2013-11-01

Migrant studies often provide clues for cancer etiology. We estimated the cancer burden among Arab Americans (ArA) by immigrant status in the metropolitan Detroit area, home to one of the highest concentrations of ArA in USA. A validated name algorithm was used to identify ArA cancer cases diagnosed 1990-2009 in the Detroit SEER database. Recorded birthplace was supplemented with imputation of nativity using birthdate and social security number. Age-adjusted, gender-specific proportional incidence ratios and 95 % confidence intervals were calculated comparing all ArA, foreign-born ArA, and US-born ArA, to non-Hispanic Whites (NHW). Foreign-born ArA males had higher proportions of multiple myeloma, leukemia, kidney, liver, stomach, and bladder cancer than NHW, while bladder cancer and leukemia were higher among US-born ArA males. For ArA women, gall bladder and thyroid cancers were proportionally higher among both foreign- and US-born compared with NHW. Stomach cancer was proportionally higher only among foreign-born women. Cancer proportional incidence patterns among ArA show some similarity to other migrant groups, with higher proportional incidences of stomach and liver cancers among foreign-born than US-born. Other patterns, such as tobacco-related cancers among ArA men and gall bladder and thyroid cancers among ArA women, will require more investigation of genetic, epigenetic, and environmental factors.

Affordances of Augmented Reality in Science Learning: Suggestions for Future Research

NASA Astrophysics Data System (ADS)

Cheng, Kun-Hung; Tsai, Chin-Chung

2013-08-01

Augmented reality (AR) is currently considered as having potential for pedagogical applications. However, in science education, research regarding AR-aided learning is in its infancy. To understand how AR could help science learning, this review paper firstly has identified two major approaches of utilizing AR technology in science education, which are named as image- based AR and location- based AR. These approaches may result in different affordances for science learning. It is then found that students' spatial ability, practical skills, and conceptual understanding are often afforded by image-based AR and location-based AR usually supports inquiry-based scientific activities. After examining what has been done in science learning with AR supports, several suggestions for future research are proposed. For example, more research is required to explore learning experience (e.g., motivation or cognitive load) and learner characteristics (e.g., spatial ability or perceived presence) involved in AR. Mixed methods of investigating learning process (e.g., a content analysis and a sequential analysis) and in-depth examination of user experience beyond usability (e.g., affective variables of esthetic pleasure or emotional fulfillment) should be considered. Combining image-based and location-based AR technology may bring new possibility for supporting science learning. Theories including mental models, spatial cognition, situated cognition, and social constructivist learning are suggested for the profitable uses of future AR research in science education.

Nitrate affects sensu-stricto germination of after-ripened Sisymbrium officinale seeds by modifying expression of SoNCED5, SoCYP707A2 and SoGA3ox2 genes.

PubMed

Carrillo-Barral, Néstor; Matilla, Angel J; Rodríguez-Gacio, María del Carmen; Iglesias-Fernández, Raquel

2014-03-01

The influence of nitrate upon the germination of Sisymbrium officinale seeds is not entirely controlled by after-ripening (AR), a process clearly influenced by nitrate. Recently, we have reported that nitrate affects sensu-stricto germination of non-AR (AR0) seeds by modifying the expression of crucial genes involved in the metabolism of GA and ABA. In this study, we demonstrate that nitrate affects also the germination of AR seeds because: (i) the AR negatively alters the ABA sensitivity being the seed more ABA-sensible as the AR is farthest from optimal (AR0 and AR20 versus AR7); in the presence of diniconazole (DZ), a competitive inhibitor of ABA 8'-hydroxylase, testa rupture is affected while the endosperm rupture is not. (ii) AR7 seed-coat rupture is not inhibited by paclobutrazol (PBZ) suggesting that nitrate can act by a mechanism GA-independent. (iii) The germination process is accelerated by nitrate, most probably by the increase in the expression of SoNCED5, SoCYP707A2 and SoGA3ox2 genes. Taken together, these and previous results demonstrate that nitrate promotes germination of AR and non-AR seeds through transcriptional changes of different genes involved in ABA and GA metabolism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Collision-Induced Absorption Spectra of Binary Mixtures of Molecular Hydrogen with Molecular Deuterium and Argon and of Pure Hydrogen, D

NASA Astrophysics Data System (ADS)

Hsieh, Chang-Tsang William

In the present research project a systematic study of the collision-induced infrared absorption (CIA) spectra of the binary mixtures of H_2 - D_2 in the region of the double fundamental vibrations of H_2 and D_2, and H_2 - Ar in the fundamental band of H_2, and of pure HD in its fundamental and first overtone regions was undertaken. The experiments were carried out with a 2.0 m high-pressure low-temperature transmission-type absorption cell at 77, 201 and 296 K at total gas densities up to 550 amagat. Infrared prism and grating spectrometers equipped with a microprocessor -controlled stepping motor were used to record the spectra. All the experimental results obtained represent first-time observations in collision-induced absorption. Collision-induced infrared absorption spectra of the double transitions of H_2(v=1>=ts 0) and D_2(v=1>=ts 0) have been observed at 77 and 201 K in the spectral region 7000-8000 cm^{-1} for total gas densities up to 550 amagat with a partial gas density ratio of 1:1 of H_2 and D_2. The observed spectra are interpreted in terms of the transitions, Q_1(J) of H_2+Q_1(J) of D _2, Q_1(J) of H_2+S _1(J) of D_2, S_1(J) of H_2 + Q_1(J) of D_2, and S_1(J) of H_2 + S_1(J) of D_2 for J = 0 and 1 for H _2 and J = 0, 1, and 2 for D_2. Analysis of the experimental absorption profiles was carried out using appropriate lineshape functions. The absorption coefficients, lineshape parameters, etc., are obtained from the analysis. Collision-induced enhancement absorption spectra of the fundamental band of H_2 in H_2 - Ar mixtures were recorded at room temperature for a base density of 72 amagat of H_2 for several partial densities of Ar up to 440 amagat. Hexadecapole-induced U transitions, U_1(1), U_1(2), Q_1(0)+U _0(1), and Q_1(1) + U_0(1) have been identified in the spectral region 5400 -6200 cm^{-1}. A "cage" model has been proposed to account for the double transitions of H_2 - H_2 in the H _2 - Ar enhancement spectra. From the analysis of the absorption profiles, the lineshape parameters and the absorption coefficients have been determined. The collision-induced absorption spectrum of the first overtone band of HD in the pure gas was observed at 77 K for gas densities up to 320 amagat. In addition to the allowed transitions P_2(1), R_2(0), and R_2(1), the CIA transitions Q_2(J)+Q_0(J), Q_1(J)+Q_1(J), Q_2(J)+S _0(J), S_2(J)+Q_0(J), Q _1(J)+S_1(J), S_2(J)+S_0(J), and S_1(J)+S_1(J) have been observed. An analysis of the observed absorption profiles has been completed. It is found that the isotropic overlap induction mechanism does not contribute to the intensity of the band and that negative contribution to the intensity of the band comes from the mixed term (2 sqrt{3}lambda_{32}exp [-(R - sigma)/rho_{32 }]times < vJmid Qmid v^' J^'>(R/a _0)^{-4}. The fundamental band of HD has been investigated at 77 K for gas densities in the range 40-310 amagat. For the first time the collision -induced transitions of the type T_1(1) + Q_0(J), Q_1(J) + T_0(1), U_1(0) + Q_0(J), Q_1(J) + U_0(0), V_1(0) + Q_0(J), and Q _1(J) + V_0(0) for HD have been identified. Here T, U, and V transitions correspond to DeltaJ = 3, 4, and 5, respectively.

Leveraging Multimodal Redundancy for Dynamic Learning, with SHACER - a Speech and HAndwriting reCognizER

DTIC Science & Technology

2007-04-01

EG’,’Visor’,’i-g’,tg,’Tier’,’i-or’,’Ii-or’,’Ti-or’,’ii-or’]) ’Arrive’,[’ARNE’,arrive,’ARNIE’,’ARCANE’,’AR Rue’,’AR Rive’,’AR RWE’,’AR RUNE ’,’AR

CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells.

PubMed

Ito, Saya; Ueno, Akihisa; Ueda, Takashi; Nakagawa, Hideo; Taniguchi, Hidefumi; Kayukawa, Naruhiro; Fujihara-Iwata, Atsuko; Hongo, Fumiya; Okihara, Koji; Ukimura, Osamu

2018-04-03

The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination.

Functional analysis of ars gene cluster of Pannonibacter indicus strain HT23(T) (DSM 23407(T)) and identification of a proline residue essential for arsenate reductase activity.

PubMed

Bandyopadhyay, Saumya; Das, Subrata K

2016-04-01

Arsenic is a naturally occurring ubiquitous highly toxic metalloid. In this study, we have identified ars gene cluster in Pannonibacter indicus strain HT23(T) (DSM 23407(T)), responsible for reduction of toxic pentavalent arsenate. The ars gene cluster is comprised of four non-overlapping open reading frames (ORFs) encoding a transcriptional regulator (ArsR), a low molecular weight protein tyrosine phosphatases (LMW-PTPase) with hypothetical function, an arsenite efflux pump (Acr3), and an arsenate reductase (ArsC). Heterologous expression of arsenic inducible ars gene cluster conferred arsenic resistance to Escherichia coli ∆ars mutant strain AW3110. The recombinant ArsC was purified and assayed. Site-directed mutagenesis was employed to ascertain the role of specific amino acids in ArsC catalysis. Pro94X (X = Ala, Arg, Cys, and His) amino acid substitutions led to enzyme inactivation. Circular dichroism spectra analysis suggested Pro94 as an essential amino acid for enzyme catalytic activity as it is indispensable for optimum protein folding in P. indicus Grx-coupled ArsC.

The role of DAB2IP in androgen receptor activation during prostate cancer progression.

PubMed

Wu, K; Liu, J; Tseng, S-F; Gore, C; Ning, Z; Sharifi, N; Fazli, L; Gleave, M; Kapur, P; Xiao, G; Sun, X; Oz, O K; Min, W; Alexandrakis, G; Yang, C-R; Hsieh, C-L; Wu, H-C; He, D; Xie, D; Hsieh, J-T

2014-04-10

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP(-/-) mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.

CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells

PubMed Central

Ito, Saya; Ueno, Akihisa; Ueda, Takashi; Nakagawa, Hideo; Taniguchi, Hidefumi; Kayukawa, Naruhiro; Fujihara-Iwata, Atsuko; Hongo, Fumiya; Okihara, Koji; Ukimura, Osamu

2018-01-01

The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination. PMID:29707137

ACK1/TNK2 Regulates Histone H4 Tyr88-phosphorylation and AR Gene Expression in Castration-Resistant Prostate Cancer.

PubMed

Mahajan, Kiran; Malla, Pavani; Lawrence, Harshani R; Chen, Zhihua; Kumar-Sinha, Chandan; Malik, Rohit; Shukla, Sudhanshu; Kim, Jongphil; Coppola, Domenico; Lawrence, Nicholas J; Mahajan, Nupam P

2017-06-12

The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription. Reversal of the pY88-H4 epigenetic marks by the ACK1 inhibitor (R)-9bMS-sensitized naive and enzalutamide-resistant prostate cancer cells and reduced AR and AR-V7 levels to mitigate CRPC tumor growth. Thus, a feedforward ACK1/pY88-H4/WDR5/MLL2/AR epigenetic circuit drives CRPC and is necessary for maintenance of the malignant state. Copyright © 2017 Elsevier Inc. All rights reserved.

AR copy number and AR signaling-directed therapies in castration-resistant prostate cancer.

PubMed

Salvi, Samanta; Conteduca, Vincenza; Lolli, Cristian; Testoni, Sara; Casadio, Valentina; Zaccheroni, Andrea; Rossi, Lorena; Burgio, Salvatore Luca; Menna, Cecilia; Schepisi, Giuseppe; De Giorgi, Ugo

2017-11-22

Adaptive upregulation of androgen receptor (AR) is the most common event involved in the progression from hormone sensitive to castration-resistant prostate cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR copy number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Outcomes of CRPC patients are reported to be highly variable as consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate cancer

PubMed Central

Hu, Qiang; Senapati, Dhirodatta; Venkadakrishnan, Varadha Balaji; Wang, Dan; DePriest, Adam D; Schlanger, Simon E; Ben-Salem, Salma; Valenzuela, Malyn May; Willard, Belinda; Mudambi, Shaila; Swetzig, Wendy M; Das, Gokul M; Shourideh, Mojgan; Koochekpour, Shahriah; Falzarano, Sara Moscovita; Magi-Galluzzi, Cristina; Yadav, Neelu; Chen, Xiwei; Lao, Changshi; Wang, Jianmin; Billaud, Jean-Noel

2017-01-01

Standard treatment for metastatic prostate cancer (CaP) prevents ligand-activation of androgen receptor (AR). Despite initial remission, CaP progresses while relying on AR. AR transcriptional output controls CaP behavior and is an alternative therapeutic target, but its molecular regulation is poorly understood. Here, we show that action of activated AR partitions into fractions that are controlled preferentially by different coregulators. In a 452-AR-target gene panel, each of 18 clinically relevant coregulators mediates androgen-responsiveness of 0–57% genes and acts as a coactivator or corepressor in a gene-specific manner. Selectivity in coregulator-dependent AR action is reflected in differential AR binding site composition and involvement with CaP biology and progression. Isolation of a novel transcriptional mechanism in which WDR77 unites the actions of AR and p53, the major genomic drivers of lethal CaP, to control cell cycle progression provides proof-of-principle for treatment via selective interference with AR action by exploiting AR dependence on coregulators. PMID:28826481

Ar-Ar Thermochronlogy of Apollo 12 Impact-Melt Breccia 12033,638-1

NASA Technical Reports Server (NTRS)

Crow, C. A.; Cassata, W. S.; Jolliff, B. L.; Ziegler, R. A.; Borg, L. E.; Shearer, C. K.

2017-01-01

We have undertaken an Ar-Ar thermochronology investigation as part of a coordinated multichronometer analysis of a single Apollo 12 impact- melt breccia to demonstrate the wide range of information that can be obtained for a single complex rock. This has implications for the age of formation, component makeup, and subsequent impact/shock and exposure history of the sample. This study also serves as a capabilities demonstration for the proposed MoonRise Mission [1]. The goal of this investigation is to elucidate the history of this sample through coordinated 40Ar*/39Ar, Sm-Nd, Rb-Sr and zircon 207Pb-206Pb ages along with geochemical and petrographic context on a relatively small (approximately 450 mg) sample. Here, we report preliminary results of the Ar-Ar thermochronology.

(Ar-39)-(Ar-40) dating of mesosiderites - Evidence for major parent body disruption less than 4 Ga ago

NASA Technical Reports Server (NTRS)

Bogard, D. D.; Jordan, J. L.; Garrison, D. H.; Mittlefehldt, D.

1990-01-01

The (Ar-39) (Ar-40) chronologies were determined for 14 different mesosiderites representing the full range of classification according to recrystallization, and these chronologies were compared with analogous data for other meteorite types and for lunar highland rocks. Results of Ar-Ar chronologies indicate the history of a degassing of Ar due to a major thermal event that occurred less than 3.9 Ga ago; this event is not the metal-silicate mixing event, which is known to have occurred earlier than 4.4 Ga ago. It is suggested that a major collisional disruption-reassembly event less than 3.9 Ga ago took place, leaving the metal-silicate breccias buried under tens of kilometers of rubble, where they cooled slowly through the Ar closure temperatures.

Functional characterization of a second pedal peptide/orcokinin‐type neuropeptide signaling system in the starfish Asterias rubens

PubMed Central

Lin, Ming; Egertová, Michaela; Zampronio, Cleidiane G.; Jones, Alexandra M.

2017-01-01

Abstract Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK‐type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK‐type precursors: an SMP‐type precursor (A. rubens PP‐like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed analysis of ArPPLNP1 expression in A. rubens and here we report the first functional characterization ArPPLNP2‐derived neuropeptides. Sequencing of a cDNA encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides (ArPPLN2a‐k), the structures of several of which were confirmed using mass spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived from this precursor using mRNA in situ hybridization and immunohistochemistry revealed a widespread distribution, including expression in radial nerve cords, circumoral nerve ring, digestive system, tube feet and innervation of interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2‐derived neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body wall‐associated apical muscle, contrasting with the relaxing effect of ArPPLN1b (ArSMP) on these preparations. ArPPLN2h does, however, cause dose‐dependent relaxation of cardiac stomach preparations, with greater potency/efficacy than ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In conclusion, there are similarities in the expression patterns of ArPPLNP1 and ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides derived from these two PP/OK‐type precursors in starfish. PMID:29218721

Functional characterization of a second pedal peptide/orcokinin-type neuropeptide signaling system in the starfish Asterias rubens.

PubMed

Lin, Ming; Egertová, Michaela; Zampronio, Cleidiane G; Jones, Alexandra M; Elphick, Maurice R

2018-04-01

Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK-type precursors: an SMP-type precursor (A. rubens PP-like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed analysis of ArPPLNP1 expression in A. rubens and here we report the first functional characterization ArPPLNP2-derived neuropeptides. Sequencing of a cDNA encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides (ArPPLN2a-k), the structures of several of which were confirmed using mass spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived from this precursor using mRNA in situ hybridization and immunohistochemistry revealed a widespread distribution, including expression in radial nerve cords, circumoral nerve ring, digestive system, tube feet and innervation of interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2-derived neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body wall-associated apical muscle, contrasting with the relaxing effect of ArPPLN1b (ArSMP) on these preparations. ArPPLN2h does, however, cause dose-dependent relaxation of cardiac stomach preparations, with greater potency/efficacy than ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In conclusion, there are similarities in the expression patterns of ArPPLNP1 and ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides derived from these two PP/OK-type precursors in starfish. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Atmospheric River impacts in British Columbia and the Pacific Northwest on 22-24 January 2015 during the CalWater 2015 field campaign

NASA Astrophysics Data System (ADS)

Gaggini, N. G.; Spackman, J. R.; Neiman, P. J.; White, A. B.; Fairall, C. W.; Barnet, C.; Gambacorta, A.; Hughes, M.

2015-12-01

Over 30 dropsonde transects were performed across atmospheric rivers (ARs) over the eastern Pacific during CalWater 2015. An event in late January allowed first-of-its-kind coordinated dropsonde transects of an AR using the NOAA G-IV aircraft in tandem with the NOAA Ronald H. Brown (RHB), which observed the marine boundary layer during the passage of this major AR. Dropsonde data collected on 22 January 2015 sampled the early stages of the AR, when the AR began making landfall near Vancouver Island, British Columbia. At the same time the RHB collected precipitation and oceanic moisture flux measurements on the warm side of the AR. A second flight on 24 January 2015 sampled the later stages of the AR, again passing over the RHB stationed beneath the AR. During this later period, the AR axis of moisture shifted north-northeast and fanned out along the coast, affecting regions from Northern Washington to Southern Alaska. Multi-day landfalling AR conditions led to flooding in British Columbia and northern Washington. The influence of the coastal orography combined with the shift in AR orientation is examined to understand the orographic control of precipitation that triggered the flooding. In addition, cross section analysis of the AR using dropsonde and reanalysis data are used to better understand the synoptic influences, water vapor transport, and moisture evolution during the lifecycle of the AR. To gain greater insight into AR development and prolonged AR conditions that led to enhanced flooding, a comparison of aircraft and ship data from CalWater 2015 and NOAA Unique CrIS/ATMS Processing System (NUCAPS) retrievals (integrated water vapor, vertical temperature and moisture profiles, and an experimental ATMS-only rain rate product) will be compared for the 22-24 January period.

An unusual Tn21-like transposon containing an ars operon is present in highly arsenic-resistant strains of the biomining bacterium Acidithiobacillus caldus.

PubMed

Tuffin, I Marla; de Groot, Peter; Deane, Shelly M; Rawlings, Douglas E

2005-09-01

A transposon, TnAtcArs, that carries a set of arsenic-resistance genes was isolated from a strain of the moderately thermophilic, sulfur-oxidizing, biomining bacterium Acidithiobacillus caldus. This strain originated from a commercial plant used for the bio-oxidation of gold-bearing arsenopyrite concentrates. Continuous selection for arsenic resistance over many years had made the bacterium resistant to high concentrations of arsenic. Sequence analysis indicated that TnAtcArs is 12 444 bp in length and has 40 bp terminal inverted repeat sequences and divergently transcribed resolvase and transposase genes that are related to the Tn21-transposon subfamily. A series of genes consisting of arsR, two tandem copies of arsA and arsD, two ORFs (7 and 8) and arsB is situated between the resolvase and transposase genes. Although some commercial strains of At. caldus contained the arsDA duplication, when transformed into Escherichia coli, the arsDA duplication was unstable and was frequently lost during cultivation or if a plasmid containing TnAtcArs was conjugated into a recipient strain. TnAtcArs conferred resistance to arsenite and arsenate upon E. coli cells. Deletion of one copy of arsDA had no noticeable effect on resistance to arsenite or arsenate in E. coli. ORFs 7 and 8 had clear sequence similarity to an NADH oxidase and a CBS-domain-containing protein, respectively, but their deletion did not affect resistance to arsenite or arsenate in E. coli. TnAtcArs was actively transposed in E. coli, but no increase in transposition frequency in the presence of arsenic was detected. Northern hybridization and reporter gene studies indicated that although ArsR regulated the 10 kb operon containing the arsenic-resistance genes in response to arsenic, ArsR had no effect on the regulation of genes associated with transposition activity.

14-3-3η Amplifies Androgen Receptor Actions in Prostate Cancer

PubMed Central

Titus, Mark A.; Tan, Jiann-an; Gregory, Christopher W.; Ford, O. Harris; Subramanian, Romesh R.; Fu, Haian; Wilson, Elizabeth M.; Mohler, James L.; French, Frank S.

2009-01-01

Purpose Androgen receptor (AR) abundance and AR-regulated gene expression in castration-recurrent prostate cancer (CaP) are indicative of AR activation in the absence of testicular androgen. AR transactivation of target genes in castration-recurrent CaP occurs in part through mitogen signaling that amplifies the actions of AR and its coregulators. Herein we report on the role of 14-3-3η in AR action. Experimental Design and Results AR and 14-3-3η co-localized in COS cell nuclei with and without androgen and 14-3-3η promoted AR nuclear localization in the absence of androgen. 14-3-3η interacted with AR in cell-free binding and coimmunoprecipitation assays. In the recurrent human CaP cell line, CWR-R1, native endogenous AR transcriptional activation was stimulated by 14-3-3η at low DHT concentrations and was increased by EGF. Moreover, the DHT and EGF dependent increase in AR transactivation was inhibited by a dominant negative 14-3-3η. In the CWR22 CaP xenograft model, 14-3-3η expression was increased by androgen, suggesting a feed-forward mechanism that potentiates both 14-3-3η and AR actions. 14-3-3η mRNA and protein decreased following castration of tumor bearing mice and increased in tumors of castrate mice after treatment with testosterone. CWR22 tumors that recurred 5 months after castration contained 14-3-3η levels similar to the androgen-stimulated tumors removed before castration. In a human prostate tissue microarray of clinical specimens, 14-3-3η localized with AR in nuclei and the similar amounts expressed in castration-recurrent CaP, androgen-stimulated CaP and benign prostatic hyperplasia were consistent with AR activation in recurrent CaP. Conclusion 14-3-3η enhances androgen and mitogen induced AR transcriptional activity in castration-recurrent CaP. PMID:19996220

Foraging Parameters Influencing the Detection and Interpretation of Area-Restricted Search Behaviour in Marine Predators: A Case Study with the Masked Booby

PubMed Central

Sommerfeld, Julia; Kato, Akiko; Ropert-Coudert, Yan; Garthe, Stefan; Hindell, Mark A.

2013-01-01

Identification of Area-restricted search (ARS) behaviour is used to better understand foraging movements and strategies of marine predators. Track-based descriptive analyses are commonly used to detect ARS behaviour, but they may be biased by factors such as foraging trip duration or non-foraging behaviours (i.e. resting on the water). Using first-passage time analysis we tested if (I) daylight resting at the sea surface positions falsely increase the detection of ARS behaviour and (II) short foraging trips are less likely to include ARS behaviour in Masked Boobies Sula dactylatra. We further analysed whether ARS behaviour may be used as a proxy to identify important feeding areas. Depth-acceleration and GPS-loggers were simultaneously deployed on chick-rearing adults to obtain (1) location data every 4 minutes and (2) detailed foraging activity such as diving rates, time spent sitting on the water surface and in flight. In 82% of 50 foraging trips, birds adopted ARS behaviour. In 19.3% of 57 detected ARS zones, birds spent more than 70% of total ARS duration resting on the water, suggesting that these ARS zones were falsely detected. Based on generalized linear mixed models, the probability of detecting false ARS zones was 80%. False ARS zones mostly occurred during short trips in close proximity to the colony, with low or no diving activity. This demonstrates the need to account for resting on the water surface positions in marine animals when determining ARS behaviour based on foraging locations. Dive rates were positively correlated with trip duration and the probability of ARS behaviour increased with increasing number of dives, suggesting that the adoption of ARS behaviour in Masked Boobies is linked to enhanced foraging activity. We conclude that ARS behaviour may be used as a proxy to identify important feeding areas in this species. PMID:23717471

Stilbene Induced Inhibition of Androgen Receptor Dimerization: Implications for AR and ARΔLBD-Signalling in Human Prostate Cancer Cells

PubMed Central

Streicher, Wolfgang; Luedeke, Manuel; Azoitei, Anca; Zengerling, Friedemann; Herweg, Alexander; Genze, Felicitas; Schrader, Mark G.; Schrader, Andres J.; Cronauer, Marcus V.

2014-01-01

Background Advanced castration resistant prostate cancer (CRPC) is often characterized by an increase of C-terminally truncated, constitutively active androgen receptor (AR) variants. Due to the absence of a ligand binding domain located in the AR-C-terminus, these receptor variants (also termed ARΔLBD) are unable to respond to all classical forms of endocrine treatments like surgical/chemical castration and/or application of anti-androgens. Methodology In this study we tested the effects of the naturally occurring stilbene resveratrol (RSV) and (E)-4-(2, 6-Difluorostyryl)-N, N-dimethylaniline, a fluorinated dialkylaminostilbene (FIDAS) on AR- and ARΔLBD in prostate cancer cells. The ability of the compounds to modulate transcriptional activity of AR and the ARΔLBD-variant Q640X was shown by reporter gene assays. Expression of endogenous AR and ARΔLBD mRNA and protein levels were determined by qRT-PCR and Western Blot. Nuclear translocation of AR-molecules was analyzed by fluorescence microscopy. AR and ARΔLBD/Q640X homo-/heterodimer formation was assessed by mammalian two hybrid assays. Biological activity of both compounds in vivo was demonstrated using a chick chorioallantoic membrane xenograft assay. Results The stilbenes RSV and FIDAS were able to significantly diminish AR and Q640X-signalling. Successful inhibition of the Q640X suggests that RSV and FIDAS are not interfering with the AR-ligand binding domain like all currently available anti-hormonal drugs. Repression of AR and Q640X-signalling by RSV and FIDAS in prostate cancer cells was caused by an inhibition of the AR and/or Q640X-dimerization. Although systemic bioavailability of both stilbenes is very low, both compounds were also able to downregulate tumor growth and AR-signalling in vivo. Conclusion RSV and FIDAS are able to inhibit the dimerization of AR and ARΔLBD molecules suggesting that stilbenes might serve as lead compounds for a novel generation of AR-inhibitors. PMID:24887556

Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer.

PubMed

Markowski, Mark C; Silberstein, John L; Eshleman, James R; Eisenberger, Mario A; Luo, Jun; Antonarakis, Emmanuel S

2017-01-01

A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice. In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC- (28%), CTC+/AR-V7- (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015). Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported thatmenwithAR-V7+results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

Associated reactions during a visual pursuit position tracking task in hemiplegic and quadriplegic cerebral palsy.

PubMed

Chiu, Hsiu-Ching; Halaki, Mark; O'Dwyer, Nicholas

2013-04-30

Most previous studies of associated reactions (ARs) in people with cerebral palsy have used observation scales, such as recording the degree of movement through observation. The sensitive quantitative method can detect ARs that are not amply visible. The aim of this study was to provide quantitative measures of ARs during a visual pursuit position tracking task. Twenty-three hemiplegia (H) (mean +/- SD: 21y 8m +/- 11y 10m), twelve quadriplegia (Q) (21y 5m +/- 10y 3m) and twenty-two subjects with normal development (N) (21y 2m +/- 10y 10m) participated in the study. An upper limb visual pursuit tracking task was used to study ARs. The participants were required to follow a moving target with a response cursor via elbow flexion and extension movements. The occurrence of ARs was quantified by the overall coherence between the movements of tracking and non-tracking limbs and the amount of movement due to ARs was quantified by the amplitude of movement the non-tracking limbs. The amplitude of movement of the non-tracking limb indicated that the amount of ARs was larger in the Q group than the H and N groups with no significant differences between the H and N groups. The amplitude of movement of the non-tracking limb was larger during non-dominant than dominant tracking in all three groups. Some movements in the non-tracking limb were correlated with the tracking limb (correlated ARs) and some movements that were not correlated with the tracking limb (uncorrelated ARs). The correlated ARs comprised less than 40% of the total ARs for all three groups. Correlated ARs were negatively associated with clinical evaluations, but not the uncorrelated ARs. The correlated and uncorrelated ARs appear to have different relationships with clinical evaluations, implying the effect of ARs on upper limb activities could be varied.

Foraging parameters influencing the detection and interpretation of area-restricted search behaviour in marine predators: a case study with the masked booby.

PubMed

Sommerfeld, Julia; Kato, Akiko; Ropert-Coudert, Yan; Garthe, Stefan; Hindell, Mark A

2013-01-01

Identification of Area-restricted search (ARS) behaviour is used to better understand foraging movements and strategies of marine predators. Track-based descriptive analyses are commonly used to detect ARS behaviour, but they may be biased by factors such as foraging trip duration or non-foraging behaviours (i.e. resting on the water). Using first-passage time analysis we tested if (I) daylight resting at the sea surface positions falsely increase the detection of ARS behaviour and (II) short foraging trips are less likely to include ARS behaviour in Masked Boobies Sula dactylatra. We further analysed whether ARS behaviour may be used as a proxy to identify important feeding areas. Depth-acceleration and GPS-loggers were simultaneously deployed on chick-rearing adults to obtain (1) location data every 4 minutes and (2) detailed foraging activity such as diving rates, time spent sitting on the water surface and in flight. In 82% of 50 foraging trips, birds adopted ARS behaviour. In 19.3% of 57 detected ARS zones, birds spent more than 70% of total ARS duration resting on the water, suggesting that these ARS zones were falsely detected. Based on generalized linear mixed models, the probability of detecting false ARS zones was 80%. False ARS zones mostly occurred during short trips in close proximity to the colony, with low or no diving activity. This demonstrates the need to account for resting on the water surface positions in marine animals when determining ARS behaviour based on foraging locations. Dive rates were positively correlated with trip duration and the probability of ARS behaviour increased with increasing number of dives, suggesting that the adoption of ARS behaviour in Masked Boobies is linked to enhanced foraging activity. We conclude that ARS behaviour may be used as a proxy to identify important feeding areas in this species.

Virtual Reality and Augmented Reality in Plastic Surgery: A Review.

PubMed

Kim, Youngjun; Kim, Hannah; Kim, Yong Oock

2017-05-01

Recently, virtual reality (VR) and augmented reality (AR) have received increasing attention, with the development of VR/AR devices such as head-mounted displays, haptic devices, and AR glasses. Medicine is considered to be one of the most effective applications of VR/AR. In this article, we describe a systematic literature review conducted to investigate the state-of-the-art VR/AR technology relevant to plastic surgery. The 35 studies that were ultimately selected were categorized into 3 representative topics: VR/AR-based preoperative planning, navigation, and training. In addition, future trends of VR/AR technology associated with plastic surgery and related fields are discussed.

Virtual Reality and Augmented Reality in Plastic Surgery: A Review

PubMed Central

Kim, Youngjun; Kim, Hannah

2017-01-01

Recently, virtual reality (VR) and augmented reality (AR) have received increasing attention, with the development of VR/AR devices such as head-mounted displays, haptic devices, and AR glasses. Medicine is considered to be one of the most effective applications of VR/AR. In this article, we describe a systematic literature review conducted to investigate the state-of-the-art VR/AR technology relevant to plastic surgery. The 35 studies that were ultimately selected were categorized into 3 representative topics: VR/AR-based preoperative planning, navigation, and training. In addition, future trends of VR/AR technology associated with plastic surgery and related fields are discussed. PMID:28573091

A Novel Role for the Receptor of the Complement Cleavage Fragment C5a, C5aR1, in CCR5-Mediated Entry of HIV into Macrophages.

PubMed

Moreno-Fernandez, Maria E; Aliberti, Julio; Groeneweg, Sander; Köhl, Jörg; Chougnet, Claire A

2016-04-01

The complement system is an ancient pattern recognition system that becomes activated during all stages of HIV infection. Previous studies have shown that C5a can enhance the infection of monocyte-derived macrophages and T cells indirectly through the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and the attraction of dendritic cells. C5a exerts its multiple biologic functions mainly through activation of C5a receptor 1 (C5aR1). Here, we assessed the role of C5aR1 as an enhancer of CCR5-mediated HIV infection. We determined CCR5 and C5aR1 heterodimer formation in myeloid cells and the impact of C5aR1 blockade on HIV entry and genomic integration. C5aR1/CCR5 heterodimer formation was identified by immunoprecipitation and western blotting. THP-1 cells and monocyte-derived macrophages (MDM) were infected by R5 laboratory strains or HIV pseudotyped for the vesicular stomatitis virus (VSV) envelope. Levels of integrated HIV were measured by quantitative PCR after targeting of C5aR1 by a C5aR antagonist, neutralizing C5aR1 monoclonal antibody (mAb) or hC5a. C5aR1 was also silenced by specific siRNA prior to viral entry. We found that C5aR1 forms heterodimers with the HIV coreceptor CCR5 in myeloid cells. Targeting C5aR1 significantly decreased integration by R5 viruses but not by VSV-pseudotyped viruses, suggesting that C5aR1 is critical for viral entry. The level of inhibition achieved with C5aR1-blocking reagents was comparable to that of CCR5 antagonists. Mechanistically, C5aR1 targeting decreased CCR5 expression. MDM from CCR5Δ32 homozygous subjects expressed levels of C5aR1 similar to CCR5 WT individuals, suggesting that mere C5aR1 expression is not sufficient for HIV infection. HIV appeared to preferentially enter THP-1 cells expressing high levels of both C5aR1 and CCR5. Targeted reduction of C5aR1 expression in such cells reduced HIV infection by ~50%. Our data thus suggest that C5aR1 acts as an enhancer of CCR5-mediated HIV entry into macrophages, the targeting of which may prove useful to reduce HIV infection by R5 strains.

Superoutburst of CR Bootis: Estimation of mass ratio of a typical AM CVn star by stage A superhumps

NASA Astrophysics Data System (ADS)

Isogai, Keisuke; Kato, Taichi; Ohshima, Tomohito; Kasai, Kiyoshi; Oksanen, Arto; Masumoto, Kazunari; Fukushima, Daiki; Maeda, Kazuki; Kawabata, Miho; Matsuda, Risa; Kojiguchi, Naoto; Sugiura, Yuki; Takeda, Nao; Matsumoto, Katsura; Itoh, Hiroshi; Pavlenko, Elena P.; Antonyuk, Kirill; Antonyuk, Oksana; Pit, Nikolai; Sosnovskij, Aleksei; Baklanov, Alex; Babina, Julia; Sklyanov, Aleksandr; Kiyota, Seiichiro; Hambsch, Franz-Josef; Littlefield, Colin; Maeda, Yutaka; Cook, Lewis M.; Masi, Gianluca; Dubovsky, Pavol A.; Novák, Rudolf; Dvorak, Shawn; Imada, Akira; Nogami, Daisaku

2016-08-01

We report on two superoutbursts of the AM CVn-type object CR Boo in 2014 April-March and 2015 May-June. A precursor outburst accompanied both of these superoutbursts. During the rising branch of the main superoutburst in 2014, we detected growing superhumps (stage A superhumps) whose period was 0.017669(24) d. Assuming that this period reflects the dynamical precession rate at the radius of the 3:1 resonance, we could estimate the mass ratio (q = M2/M1) of 0.101(4) by using the stage A superhump period and the orbital period of 0.0170290(6) d. This mass ratio is consistent with that expected from the theoretical evolutionary model of AM CVn-type objects. The detection of precursor outbursts and stage A superhumps is the second case in AM CVn-type objects. There are two interpretations of the outbursts of AM CVn-type objects. One is a dwarf nova (DN) outbursts analogy, which suggets that the outbursts are caused by thermal and tidal instabilities. Another is the VY Scl-type variation, which suggests that the outbursts are caused by the variation of the mass-transfer rate of the secondary.This detection of the superhump variations strongly supports the former interpretation.

Stability of triangular points in the elliptic restricted three-body problem with oblateness up to zonal harmonic J4 of both primaries

NASA Astrophysics Data System (ADS)

Singh, Jagadish; Tyokyaa, Richard K.

2016-10-01

In this paper, we study the locations and stability of triangular points in the elliptic restricted three-body problem when both primaries are taken as oblate spheroids with oblateness up to J4. The positions of the triangular points are seen to be affected by oblateness of the primaries and the eccentricity of their orbits. The triangular points are conditionally stable for 0<μ<μc0<μ<μc and unstable for μc≤μ≤12μc≤μ≤12, where μcμc is the critical mass parameter depending on the oblateness coefficients J2iJ2i (i =1,2) and the eccentricity of the orbits. We further observe that both coefficients J2 and J4, semi-major axis and the eccentricity have destabilizing tendencies resulting in a decrease in the size of the region of stability with an increase in the parameters involved. Knowing that, in general, the triangular equilibrium points are stable for 0<μ<μc0<μ<μc, in particular systems (Alpha Centauri, X1X1 Bootis, Sirius and Kruger 60) this does not hold and such points are unstable.

Boyfriends and booty calls: sexual partnership patterns among Canadian Aboriginal young people.

PubMed

Devries, Karen M; Free, Caroline J

2011-01-01

Sexual partnership patterns, forced sex, and condom non-use can contribute to STI risk, but little is known about these patterns among Aboriginal young people despite elevated STI risk in this group. We describe sexual relationship and condom use patterns among Canadian Aboriginal young people, and how these patterns relate to the socio-structural context as experienced by young people. We use data from in-depth individual interviews conducted in 2004 with 22 young people who reported ever having sex and who self-identified as Aboriginal in British Columbia, Canada. A thematic analysis is presented. Young people described a range of partnership patterns, including 'on-off' relationships which could have high rates of partner turnover but could sometimes be viewed as acceptable contexts for pregnancy, precluding condom use. Contextual elements beyond individual control appeared to contribute to these patterns. Migration between geographic locations was linked with risky partnership patterns, especially if it was linked with family instability or substance use problems. Sexual health interventions for this group must address partnership patterns in addition to promoting condom use. Survey research into 'migration' as a risk factor for STI transmission should consider reasons for migration. Interventions that address both individual level behaviour and the contextual elements that shape behaviour should be developed and tested.

Agricultural Research Service

MedlinePlus

... Durum Wheat Opens Door to Expand Food Uses ARS Research In Your State - choose - Alabama Alaska Arizona ... Media About ARS Work With Us Connect with ARS Sign up ARS Home USDA.gov Plain Writing ...

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

PubMed

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

PubMed

Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

2017-04-01

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

Androgen receptor signaling and mutations in prostate cancer

PubMed Central

Koochekpour, Shahriar

2010-01-01

Normal and neoplastic growth of the prostate gland are dependent on androgen receptor (AR) expression and function. Androgenic activation of the AR, in association with its coregulatory factors, is the classical pathway that leads to transcriptional activity of AR target genes. Alternatively, cytoplasmic signaling crosstalk of AR by growth factors, neurotrophic peptides, cytokines or nonandrogenic hormones may have important roles in prostate carcinogenesis and in metastatic or androgen-independent (AI) progression of the disease. In addition, cross-modulation by various nuclear transcription factors acting through basal transcriptional machinery could positively or negatively affect the AR or AR target genes expression and activity. Androgen ablation leads to an initial favorable response in a significant number of patients; however, almost invariably patients relapse with an aggressive form of the disease known as castration-resistant or hormone-refractory prostate cancer (PCa). Understanding critical molecular events that lead PCa cells to resist androgen-deprivation therapy is essential in developing successful treatments for hormone-refractory disease. In a significant number of hormone-refractory patients, the AR is overexpressed, mutated or genomically amplified. These genetic alterations maintain an active presence for a highly sensitive AR, which is responsive to androgens, antiandrogens or nonandrogenic hormones and collectively confer a selective growth advantage to PCa cells. This review provides a brief synopsis of the AR structure, AR coregulators, posttranslational modifications of AR, duality of AR function in prostate epithelial and stromal cells, AR-dependent signaling, genetic changes in the form of somatic and germline mutations and their known functional significance in PCa cells and tissues. PMID:20711217

ARS turns fifteen: la quinceañera bonita.

PubMed

Sen, Chandan K

2013-01-01

ARS was aimed at advancing the erstwhile niche field of redox biology to a more central position in research. Currently, ARS ranks first (impact factor: 8.456) in the field of redox biology. Of 8336 journals listed in Journal Citation Reports, ARS ranks 205th. The next journal in redox biology ranks 449th. ARS ranks 169th of 8336 in immediacy index. The next journal in redox biology ranks 923rd. Thus, ARS is the primary source of hot papers in redox sciences and healthcare. To grow footprint and overall impact, ARS has nearly doubled the annual publication volume from roughly 200 to 400 in one year. Because the manuscript volume represents the denominator of the impact factor calculation, such a sharp increase in volume would be predicted to a proportionally lower impact factor. Because of the robust current upward momentum, ARS will be affected less than that predicted by simple arithmetic and will maintain its top position even after such aggressive volume expansion. As another year passes, the additional manuscripts will get more time to be cited, and therefore the impact factor is expected to bounce back resulting in a much stronger journal with a substantially enhanced overall presence. ARS currently publishes 36 issues annually as two series: ARS-Discoveries, and ARS-Therapeutics. Redox biology does have the potential of major health impact. ARS-Therapeutics is the first and only forum dedicated to highlight that strength. I am grateful to the global redox village for their unreserved support to raise ARS and this fascinating field of redox research and healthcare. Antioxid. Redox Signal. 18, 1-4.

Current Allergic Rhinitis Experiences Survey (CARES): Health-care practitioners' awareness, attitudes and practices.

PubMed

Blaiss, Michael S; Fromer, Leonard M; Jacob-Nara, Juby A; Long, Randall M; Mannion, Karen M; Lauersen, Lori A

2014-01-01

Allergic rhinitis (AR) is a common health problem in the United States, with significant comorbidities and impairment of quality of life despite the availability of many prescription (Rx) and over-the-counter (OTC) medications. The health-care practitioners (HCPs) arm of the Current Allergic Rhinitis Experiences Survey (CARES) assessed HCPs' perceptions about the current management of AR. This U.S.-based national survey included 375 primary care physicians and 375 nurse practitioners/physician assistants. Participants were screened to ensure that they treat ≥15 AR sufferers per month during allergy season. The majority of HCPs (86%) agreed that AR patients can easily recognize allergy symptoms after diagnosis and that 57% of their patients come to them self-recognizing their symptoms. A total of 82% strongly agreed that AR sufferers are primarily diagnosed via history and physical and do not typically undergo diagnostic testing until after pharmacologic intervention. HCPs reported that 63-77% of AR sufferers can easily manage AR once treatment is established. According to surveyed HCPs, OTC medication should precede an Rx medication for AR management. A total of 82% HCPs considered intranasal steroids (INSs) to be the gold standard AR treatment and have minimal safety concerns about INS use. HCPs perceive that patients can easily recognize and self-manage their AR symptoms. Patient history/symptoms and physical examination are the primary methods of AR diagnosis. INSs are considered the gold standard for treatment of AR. However, most HCPs feel OTC medication should be tried before Rx medication for AR management.

Insights into arsenic multi-operons expression and resistance mechanisms in Rhodopseudomonas palustris CGA009

PubMed Central

Zhao, Chungui; Zhang, Yi; Chan, Zhuhua; Chen, Shicheng; Yang, Suping

2015-01-01

Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III)) concentrations (up to 1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase (55 h). ars2 operon was actively expressed even at the low concentration of As(III) (0.01 μM), whereas the ars3 operon was expressed at 1.0 μM of As(III), indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase). Arsenic speciation analysis demonstrated that R. palustris could reduce As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic reduction and methylating arsenic mechanism, while the latter might occur with the presence of higher concentrations of arsenic. PMID:26441915

A m-ary linear feedback shift register with binary logic

NASA Technical Reports Server (NTRS)

Perlman, M. (Inventor)

1973-01-01

A family of m-ary linear feedback shift registers with binary logic is disclosed. Each m-ary linear feedback shift register with binary logic generates a binary representation of a nonbinary recurring sequence, producible with a m-ary linear feedback shift register without binary logic in which m is greater than 2. The state table of a m-ary linear feedback shift register without binary logic, utilizing sum modulo m feedback, is first tubulated for a given initial state. The entries in the state table are coded in binary and the binary entries are used to set the initial states of the stages of a plurality of binary shift registers. A single feedback logic unit is employed which provides a separate feedback binary digit to each binary register as a function of the states of corresponding stages of the binary registers.

Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP

PubMed Central

Johnsen, Sylvia Sagen; Kaino, Katrine; Sjøttem, Eva; Johansen, Terje

2011-01-01

The androgen receptor (AR) has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a transcriptional regulator that previously has been shown to enhance the activity of Pax6. In this study we have identified SPBP to act as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. Enhanced expression of Pax6 reduced the amount of SPBP associated with the probasin promoter when assayed by ChIP in HeLa cells. We mapped the interaction between both AR and SPBP, and AR and Pax6 to the DNA-binding domains of the involved proteins. Further binding studies revealed that Pax6 and SPBP compete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to molecular targeted drugs for treatment of prostate cancer. PMID:21935435

Fitness costs associated with infections of secondary endosymbionts in the cassava whitefly species Bemisia tabaci.

PubMed

Ghosh, Saptarshi; Bouvaine, Sophie; Richardson, Simon C W; Ghanim, Murad; Maruthi, M N

2018-01-01

We investigated the dual effects of bacterial infections and diseased cassava plants on the fitness and biology of the Bemisia tabaci infesting cassava in Africa. Isofemale B. tabaci colonies of sub-Saharan Africa 1-subgroup 3 (SSA1-SG3), infected with two secondary endosymbiotic bacteria Arsenophonus and Rickettsia (AR+) and those free of AR infections (AR-), were compared for fitness parameters on healthy and East African cassava mosaic virus -Uganda variant (EACMV-UG)-infected cassava plants. The whitefly fecundity and nymph development was not affected by bacterial infections or the infection of cassava by the virus. However, emergence of adults from nymphs was 50 and 17% higher by AR- on healthy and virus-infected plants, respectively, than AR+ flies. Development time of adults also was 10 days longer in AR+ than AR-. The whiteflies were further compared for acquisition and retention of EACMV-UG. Higher proportion of AR- acquired (91.8%) and retained (87.6%) the virus than AR+ (71.8, 61.2%, respectively). Similarly, the AR- flies retained higher quantities of virus (~ninefold more) than AR+. These results indicated that bacteria-free whiteflies were superior and better transmitters of EACMV-UG, as they had higher adult emergence, quicker life cycle and better virus retention abilities than those infected with bacteria.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

PubMed

Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H L; Wang, Jun; Mawji, Nasrin R; Sadar, Marianne D

2017-01-01

Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer

PubMed Central

Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H. L.; Wang, Jun; Mawji, Nasrin R.; Sadar, Marianne D.

2017-01-01

Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD. PMID:28306720

Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer.

PubMed

Khurana, Namrata; Kim, Hogyoung; Chandra, Partha K; Talwar, Sudha; Sharma, Pankaj; Abdel-Mageed, Asim B; Sikka, Suresh C; Mondal, Debasis

2017-11-01

Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1). MTT cell viability, wound-heal assay, and colony forming unit (CFU) measurements revealed that 22Rv1 cells are resistant to the anti-androgen, enzalutamide (ENZ). However, co-exposure to SFN sensitized these cells to the potent anticancer effects of ENZ (P<0.05). Immunoblot analyses showed that SFN (5-20 µM) rapidly decreases both AR-FL and AR-V7 levels, and immunofluorescence microscopy (IFM) depicted decreased AR in both cytoplasm and nucleus with SFN treatment. SFN increased both ubiquitination and proteasomal activity in 22Rv1 cells. Studies using a protein synthesis inhibitor (cycloheximide) or a proteasomal inhibitor (MG132) indicated that SFN increases both ubiquitin-mediated aggregation and subsequent proteasomal-degradation of AR proteins. Previous studies reported that SFN inhibits the chaperone activity of heat-shock protein 90 (Hsp90) and induces the nuclear factor erythroid-2-like 2 (Nrf2) transcription factor. Therefore, we investigated whether the Hsp90 inhibitor, ganetespib (G) or the Nrf2 activator, bardoxolone methyl (BM) can similarly suppress AR levels in 22Rv1 cells. Low doses of G and BM, alone or in combination, decreased both AR-FL and AR-V7 levels, and combined exposure to G+BM sensitized 22Rv1 cells to ENZ. Therefore, adjunct treatment with the phytochemical SFN or a safe pharmaceutical combination of G+BM may be effective against CRPC cells, especially those expressing AR-V7.

Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer

PubMed Central

Khurana, Namrata; Kim, Hogyoung; Chandra, Partha K.; Talwar, Sudha; Sharma, Pankaj; Abdel-Mageed, Asim B.; Sikka, Suresh C.; Mondal, Debasis

2017-01-01

Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1). MTT cell viability, wound-heal assay, and colony forming unit (CFU) measurements revealed that 22Rv1 cells are resistant to the anti-androgen, enzalutamide (ENZ). However, co-exposure to SFN sensitized these cells to the potent anticancer effects of ENZ (P<0.05). Immunoblot analyses showed that SFN (5–20 µM) rapidly decreases both AR-FL and AR-V7 levels, and immunofluorescence microscopy (IFM) depicted decreased AR in both cytoplasm and nucleus with SFN treatment. SFN increased both ubiquitination and proteasomal activity in 22Rv1 cells. Studies using a protein synthesis inhibitor (cycloheximide) or a proteasomal inhibitor (MG132) indicated that SFN increases both ubiquitin-mediated aggregation and subsequent proteasomal-degradation of AR proteins. Previous studies reported that SFN inhibits the chaperone activity of heat-shock protein 90 (Hsp90) and induces the nuclear factor erythroid-2-like 2 (Nrf2) transcription factor. Therefore, we investigated whether the Hsp90 inhibitor, ganetespib (G) or the Nrf2 activator, bardoxolone methyl (BM) can similarly suppress AR levels in 22Rv1 cells. Low doses of G and BM, alone or in combination, decreased both AR-FL and AR-V7 levels, and combined exposure to G+BM sensitized 22Rv1 cells to ENZ. Therefore, adjunct treatment with the phytochemical SFN or a safe pharmaceutical combination of G+BM may be effective against CRPC cells, especially those expressing AR-V7. PMID:28901514

Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

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

Wang, Tingting; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Chen, Man

Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a singlemore » site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination. Black-Right-Pointing-Pointer Single CpG methylation located at Pax6 binding motif regulates StAR expression.« less

Application of K-Ar Dating to the Chronology of Young Volcanic Centers

NASA Astrophysics Data System (ADS)

Lanphere, M. A.

2003-12-01

K-Ar dating and a derivative technique, 40Ar/39Ar dating, are methods of high-precision chronology applicable to young volcanic centers. Cascade volcanoes studied in detail by several USGS volcanologists, Duane Champion paleomagetist, and me include Mt. Baker, WA; Mt. Rainier, WA; Mt. Adams, WA; Mt. Hood, OR; Crater Lake, OR; and Medicine Lake, CA. For Mt. Adams using detailed geologic mapping by Hildreth and Fierstein and 74 K-Ar ages for 63 mapped units, Hildreth and Lanphere established a detailed chronology for the stratovolcano. Good agreement has been achieved for K-Ar ages and 40Ar/39Ar ages of rocks from Mt. Adams as young as 36 ka. A similar detailed chronology has been established for other Cascade volcanoes using andesites, in particular. These chronologies often take 10 years or more to develop. Major advantages of the 40Ar/39Ar technique are the ability to work with small sample sizes and the possibility to push the technique to very young ages. The Campanian Ignimbrite erupted from the Campi Flegrei crater near Naples, Italy is an example of the use of small samples. Nine incremental-heating ages were determined on samples of sanidine ranging in size from 47 mg to 67 mg. These samples yielded ages for the Campanian Ignimbrite ranging from 37.1 +/- 0.75 ka to 39.5 +/- 0.62 ka and averaging 38.1 +/- 0.8 ka. Other workers have proposed 40Ar/39Ar ages for the Campanian Ignimbrite of 37.1 +/- 0.4 ka and 39.3 +/- 0.1 ka. An example of the use of 40Ar/39Ar dating of very young samples is the Christian Era (CE) age of the Vesuvius eruption of year 79. Eight packets of sanidine weighing 213-296 mg from two localities, Casti Amanti in Pompeii and Villa Poppea in nearby Oplontis, yielded a weighted-mean incremental-heating age of 1924 +/- 66 years. The known age for the CE 79 eruption of Vesuvius is 1924 years. Earlier studies of Vesuvius by other workers yielded an 40Ar/39Ar age for the Villa Poppea locality of 1922 +/- 72 years.

40Ar/36Ar geochronology on a quadrupole mass spectrometer: Where are we going?

NASA Astrophysics Data System (ADS)

Schneider, B.; Wijbrans, J. R.; Kuiper, K. F.; Fenton, C. R.; Williams, A. J.

2009-04-01

40Ar/39Ar analysis has passed many milestones since its first application (Wänke & König, 1959). From the early all-glass Reynolds-type vacuum system to today's high quality, bakeable all-metal piping and valve systems, the evolution of ultra high vacuum systems has been considerable. Extraction systems have faced similar changes over time. Early furnaces made partially of glass were later replaced by full metal constructs containing a high temperature resistant molybdenum alloy tube and heating mechanism, sometimes contained within an insulating secondary vacuum chamber. Laser extraction techniques further refined the approach allowing very small samples or sample parts to be analyzed. The principal type of mass spectrometer used for 40Ar/36Ar geochronology is the magnetic sector instrument, which has the resolution and sensitivity necessary for measuring argon isotopes and achieving high precision over a large age range. We present 40Ar/39Ar data from basalt samples collected from a number of different locations, all obtained using the Hiden HAL Series 1000 quadrupole mass spectrometer at Vrije University, Amsterdam. We show that quadrupole technology is not only a viable option in K-Ar geochronology (Rouchon et al., 2008) but also in 40Ar/39Ar geochronology. The data was obtained from groundmass hand-picked from 200-500 um size fractions. Sample amounts of 200 to 500 mg were used for incremental heating experiments. The quality of the data is demonstrated by convergence of plateau and isochron ages, replicate analyses and by comparison to results of independent studies. Sample ages range from 40 ka to 400 ka, demonstrating the potential of quadrupole instruments for dating even very young rocks using the 40Ar/39Ar incremental heating technique. Rouchon, V., Lefevre, J.-C., Quidelleur, X., Guerin, G., Gillot, P.-Y. (2008): Nonspiked 40Ar and 36Ar quantification using a quadrupole mass spectrometer: A potential for K-Ar geochronology. International Journal of Mass Spectrometry 270, 52-61. Wänke H., König H. (1959): Eine neue Methode zur Kalium-Argon-Altersbestimmung und ihre Anwendung auf Steinmeteorite. Z. Naturforschung, 14a, 860 - 866.

Two barcodes encoded by the type-1 PDZ and by phospho-Ser312 regulate retromer/WASH-mediated sorting of the ß1-adrenergic receptor from endosomes to the plasma membrane.

PubMed

Nooh, Mohammed M; Bahouth, Suleiman W

2017-01-01

Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß 1 -AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß 1 -AR is inhibited when PKA or its substrate serine at position 312 (Ser 312 ) are inactivated. We tested the hypothesis that phospho-Ser 312 provided a second barcode for ß 1 -AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß 1 -AR trafficking. Recycling of WT ß 1 -AR or WT ß 2 -AR was dependent on targeting the retromer to endosomal membranes via SNX3 and rab7a, and on complexing the retromer to the WASH pentamer via the C-tail of FAM21 (FAM21 C ). These maneuvers however, did not inhibit the recycling of a phospho-Ser 312 ß 1 -AR mimic ((S312D) ß 1 -AR). Knockdown of the trans-acting PDZ protein sorting nexin27 (SNX27) inhibited the recycling of WT ß 1 -AR and WT ß 2 -AR, but had no effect on (S312D) ß 1 -AR∆PDZ or on phosphorylation of WT ß 1 -AR by PKA at Ser 312 . However, depletion of FKBP15, a FAM21 C -binding endosomal protein, selectively inhibited WT ß 1 -AR but not ß 2 -AR recycling, suggesting divergence might exist in GPCR trafficking roadmaps. These results indicate that two barcodes are involved in sorting WT ß 1 -AR out of early endosomes. The first and antecedent "barcode" was the "type-1 PDZ", followed by a second reversible "phospho-Ser 312 " verification "barcode". This organization allows tight regulation of ß 1 -AR density to signaling intensity in conditions associated with aberrant ß 1 -AR signaling such as in hypertension and heart failure. Copyright © 2016 Elsevier Inc. All rights reserved.

40Ar/39Ar geochronology of terrestrial pyroxene

NASA Astrophysics Data System (ADS)

Ware, Bryant; Jourdan, Fred

2018-06-01

Geochronological techniques such as U/Pb in zircon and baddeleyite and 40Ar/39Ar on a vast range of minerals, including sanidine, plagioclase, and biotite, provide means to date an array of different geologic processes. Many of these minerals, however, are not always present in a given rock, or can be altered by secondary processes (e.g. plagioclase in mafic rocks) limiting our ability to derive an isotopic age. Pyroxene is a primary rock forming mineral for both mafic and ultramafic rocks and is resistant to alteration process but attempts to date this phase with 40Ar/39Ar has been met with little success so far. In this study, we analyzed pyroxene crystals from two different Large Igneous Provinces using a multi-collector noble gas mass spectrometer (ARGUS VI) since those machines have been shown to significantly improve analytical precision compared to the previous single-collector instruments. We obtain geologically meaningful and relatively precise 40Ar/39Ar plateau ages ranging from 184.6 ± 3.9 to 182.4 ± 0.8 Ma (2σ uncertainties of ±1.8-0.4%) and 506.3 ± 3.4 Ma for Tasmanian and Kalkarindji dolerites, respectively. Those data are indistinguishable from new and/or published U-Pb and 40Ar/39Ar plagioclase ages showing that 40Ar/39Ar dating of pyroxene is a suitable geochronological tool. Scrutinizing the analytical results of the pyroxene analyses as well as comparing them to the analytical result from plagioclase of the same samples indicate pure pyroxene was dated. Numerical models of argon diffusion in plagioclase and pyroxene support these observations. However, we found that the viability of 40Ar/39Ar dating approach of pyroxene can be affected by irradiation-induced recoil redistribution between thin pyroxene exsolution lamellae and the main pyroxene crystal, hence requiring careful petrographic observations before analysis. Finally, diffusion modeling show that 40Ar/39Ar of pyroxene can be used as a powerful tool to date the formation age of mafic rocks affected by greenschist metamorphism and will likely play an important role in high temperature thermochronology.

40 CFR 52.120 - Identification of plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (i) Incorporation by reference. (A) Arizona Revised Statutes. (1) Senate Bill 1360: Section 6: ARS 15-1444-C (added), Section 7: QRS 15-1627-F (added), Section 21: ARS 49- 542-A (amended, Section 21: ARS 49-542-E (added), Section 21: ARS 49-542-J.3.(b) (amended), and Section 23: ARS 49-550-E (added...

40 CFR 52.120 - Identification of plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (i) Incorporation by reference. (A) Arizona Revised Statutes. (1) Senate Bill 1360: Section 6: ARS 15-1444-C (added), Section 7: QRS 15-1627-F (added), Section 21: ARS 49- 542-A (amended, Section 21: ARS 49-542-E (added), Section 21: ARS 49-542-J.3.(b) (amended), and Section 23: ARS 49-550-E (added...

40 CFR 52.120 - Identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (i) Incorporation by reference. (A) Arizona Revised Statutes. (1) Senate Bill 1360: Section 6: ARS 15-1444-C (added), Section 7: QRS 15-1627-F (added), Section 21: ARS 49- 542-A (amended, Section 21: ARS 49-542-E (added), Section 21: ARS 49-542-J.3.(b) (amended), and Section 23: ARS 49-550-E (added...

75 FR 61774 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Annual...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... (ARS) information collection. While the primary purpose of the ARS is to verify or to correct the North... purposes of the ARS. The ARS seeks accurate mailing and physical location addresses of establishments as... States). The ARS constitutes an information collection within the meaning of the PRA. Under the PRA, a...

40 CFR 52.120 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (i) Incorporation by reference. (A) Arizona Revised Statutes. (1) Senate Bill 1360: Section 6: ARS 15-1444-C (added), Section 7: QRS 15-1627-F (added), Section 21: ARS 49- 542-A (amended, Section 21: ARS 49-542-E (added), Section 21: ARS 49-542-J.3.(b) (amended), and Section 23: ARS 49-550-E (added...

40 CFR 52.120 - Identification of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (i) Incorporation by reference. (A) Arizona Revised Statutes. (1) Senate Bill 1360: Section 6: ARS 15-1444-C (added), Section 7: QRS 15-1627-F (added), Section 21: ARS 49- 542-A (amended, Section 21: ARS 49-542-E (added), Section 21: ARS 49-542-J.3.(b) (amended), and Section 23: ARS 49-550-E (added...

Ar-Ar Impact Heating Ages of Eucrites and Timing of the LHB

NASA Technical Reports Server (NTRS)

Bogard, Donald; Garrison, Daniel

2009-01-01

Eucrites and howardites, more than most meteorite types, show extensive impact resetting of their Ar-39-Ar-40 (K-Ar) ages approximately equal to 3.4-4.1 Ga ago, and many specimens show some disturbance of other radiometry chronometers as well. Bogard (1995) argued that this age resetting occurred on Vesta and was produced by the same general population of objects that produced many of the lunar impact basins. The exact nature of the lunar late heavy bombardment (LHB or 'cataclysm') remains controversial, but the timing is similar to the reset ages of eucrites. Neither the beginning nor ending time of the lunar LHB is well constrained. Comparison of Ar-Ar ages of brecciated eucrites with data for the lunar LHB can resolve both the origin of these impactors and the time period over which they were delivered to the inner solar system. This abstract reports some new Ar-Ar age data for eucrites, obtained since the authors' 1995 and 2003 papers.

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis.

PubMed

Castillo, Ana F; Orlando, Ulises; Helfenberger, Katia E; Poderoso, Cecilia; Podesta, Ernesto J

2015-06-15

The steroidogenic acute regulatory (StAR) protein regulates the rate-limiting step in steroidogenesis, i.e. the delivery of cholesterol from the outer (OMM) to the inner (IMM) mitochondrial membrane. StAR is a 37-kDa protein with an N-terminal mitochondrial targeting sequence that is cleaved off during mitochondrial import to yield 30-kDa intramitochondrial StAR. StAR acts exclusively on the OMM and its activity is proportional to how long it remains on the OMM. However, the precise fashion and the molecular mechanism in which StAR remains on the OMM have not been elucidated yet. In this work we will discuss the role of mitochondrial fusion and StAR phosphorylation by the extracellular signal-regulated kinases 1/2 (ERK1/2) as part of the mechanism that regulates StAR retention on the OMM and activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Static and Impulsive Models of Solar Active Regions

NASA Technical Reports Server (NTRS)

Patsourakos, S.; Klimchuk, James A.

2008-01-01

The physical modeling of active regions (ARs) and of the global coronal is receiving increasing interest lately. Recent attempts to model ARs using static equilibrium models were quite successful in reproducing AR images of hot soft X-ray (SXR) loops. They however failed to predict the bright EUV warm loops permeating ARs: the synthetic images were dominated by intense footpoint emission. We demonstrate that this failure is due to the very weak dependence of loop temperature on loop length which cannot simultaneously account for both hot and warm loops in the same AR. We then consider time-dependent AR models based on nanoflare heating. We demonstrate that such models can simultaneously reproduce EUV and SXR loops in ARs. Moreover, they predict radial intensity variations consistent with the localized core and extended emissions in SXR and EUV AR observations respectively. We finally show how the AR morphology can be used as a gauge of the properties (duration, energy, spatial dependence, repetition time) of the impulsive heating.

Age of the Hawaiian-Emperor bend

USGS Publications Warehouse

Dalrymple, G.B.; Clague, D.A.

1976-01-01

40Ar/39Ar age data on alkalic and tholeiitic basalts from Diakakuji and Kinmei Seamounts in the vicinity of the Hawaiian-Emperor bend indicate that these volcanoes are about 41 and 39 m.y. old, respectively. Combined with previously published age data on Yuryaku and Ko??ko Seamounts, the new data indicate that the best age for the bend is 42.0 ?? 1.4 m.y. Petrochemical data indicate that the volcanic rocks recovered from bend seamounts are indistinguishable from Hawaiian volcanic rocks, strengthening the hypothesis that the Hawaiian-Emperor bend is part of the Hawaiian volcanic chain. 40Ar/39Ar total fusion ages on altered whole-rock basalt samples are consistent with feldspar ages and with 40Ar/39Ar incremental heating data and appear to reflect the crystallization ages of the samples even though conventional K-Ar ages are significantly younger. The cause of this effect is not known but it may be due to low-temperature loss of 39Ar from nonretentive montmorillonite clays that have also lost 40Ar. ?? 1976.

Re-examining the surfaces of bone in boys and girls during adolescent growth: a 12-year mixed longitudinal pQCT study

PubMed Central

Gabel, Leigh; Nettlefold, Lindsay; Brasher, Penelope M.; Moore, Sarah; Ahamed, Yasmin; Macdonald, Heather M.; McKay, Heather A.

2016-01-01

We revisit Stanley Garn’s theory related to sex differences in endocortical and periosteal apposition during adolescence using a 12-year mixed longitudinal study design. We used peripheral quantitative computed tomography to examine bone parameters in 230 participants (110 boys, 120 girls; 11.0 yrs at baseline). We assessed total (Tt.Ar, mm2), cortical (Ct.Ar, mm2), and medullary canal area (Me.Ar, mm2), Ct.Ar/Tt.Ar, cortical bone mineral density (Ct.BMD, mg/cm3) and polar strength-strain index (SSIp, mm3) at the tibial midshaft (50% site). We used annual measures of height and chronological age to identify age at peak height velocity (APHV) for each participant. We compared annual accrual rates of bone parameters between boys and girls, aligned on APHV using a linear mixed effects model. At APHV, boys demonstrated greater Tt.Ar (Ratio: 1.27; 95% CI: [1.21, 1.32]), Ct.Ar (1.24; [1.18, 1.30]), Me.Ar (1.31; [1.22, 1.40]) and SSIp (1.36; [1.28, 1.45]), and less Ct.Ar/Tt.Ar (0.98; [0.96, 1.00]) and Ct.BMD (0.97; [0.96, 0.97]) compared with girls. Boys and girls demonstrated periosteal bone formation and net bone loss at the endocortical surface. Compared with girls, boys demonstrated greater annual accrual rates pre-APHV for Tt.Ar (1.18; [1.02, 1.34]) and Me.Ar (1.34; [1.11, 1.57]), lower annual accrual rates pre-APHV for Ct.Ar/Tt.Ar (0.56; [0.29, 0.83]) and Ct.BMD (−0.07; [−0.17, 0.04]) and similar annual accrual rates pre-APHV for Ct.Ar (1.10; [0.94, 1.26]) and SSIp (1.14; [0.98, 1.30]). Post-APHV, boys demonstrated similar annual accrual rates for Ct.Ar/Tt.Ar (1.01; [0.71, 1.31]) and greater annual accrual rates for all other bone parameters compared with girls (Ratio: 1.23 – 2.63; 95% CI: 1.11 to 3.45). Our findings support those of Garn and others of accelerated periosteal apposition during adolescence, more evident in boys than girls. However, our findings challenge the notion of greater endocortical apposition in girls, suggesting instead that girls experience diminished endocortical resorption compared with boys. PMID:26058373

Expression of beta 3-adrenoceptor mRNA in rat tissues.

PubMed

Evans, B A; Papaioannou, M; Bonazzi, V R; Summers, R J

1996-01-01

1. This study examines the expression of beta 3-adrenoceptor messenger RNA (beta 3-AR mRNA) in rat tissues to allow comparison with atypical beta-adrenoceptors determined by functional and radioligand binding techniques. 2. A reverse transcription/polymerase chain reaction protocol has been developed for determining the relative amounts of beta 3-AR mRNA in rat tissues. 3. Measurement of adipsin and uncoupling protein (UCP) mRNA was used to examine all tissues for the presence of white and brown adipose tissue which may contribute beta 3-AR mRNA. 4. The beta 3-AR mRNA is expressed at high levels in brown and white adipose tissue, stomach fundus, the longitudinal/circular smooth muscle of both colon and ileum, and colon submucosa. There was substantial expression of adipsin in colon submucosa and moderate expression in fundus, suggesting that in these regions at least some of the beta 3-AR signal may be contributed by fat. Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin. Ileum mucosa and submucosa showed low but readily detectable levels of beta 3-AR. 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver. These results raise the possibility that the atypical beta-AR demonstrated by functional and/or binding studies in muscle and in heart is not the beta 3-AR. 6. By use of two different sets of primers for amplification of beta 3-AR cDNA, no evidence was found for differential splicing of the mRNA in any of the tissues examined. 7. The detection of beta 3-AR mRNA in the gut mucosa and submucosa suggests that in addition to its established roles in lipolysis, thermogenesis and regulation of gut motility beta 3-AR may subserve other functions in the gastrointestinal tract. The absence of beta 3-AR mRNA in rat heart or its presence with adipsin in skeletal muscle suggests that atypical beta-adrenoceptor responses in heart and skeletal muscle are unlikely to be mediated by beta 3-AR.

The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men.

PubMed

Alevizaki, M; Cimponeriu, A T; Garofallaki, M; Sarika, H L; Alevizaki, C C; Papamichael, C; Philippou, G; Anastasiou, E A; Lekakis, J P; Mavrikakis, M

2003-12-01

The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.

ARS-Media for excel instruction manual

USDA-ARS?s Scientific Manuscript database

ARS-Media for Excel Instruction Manual is the instruction manual that explains how to use the Excel spreadsheet ARS-Media for Excel application. ARS-Media for Excel Instruction Manual is provided as a pdf file....

Publications - RDF 2015-10 | Alaska Division of Geological & Geophysical

Science.gov Websites

Keywords 40Ar/39Ar; Age Dates; Analyses; Analyses and Sampling; Analytical Lab Results; Analytical Results ; Ar-Ar; Bedrock; Bedrock Geology; Cretaceous; Early Jurassic; Eocene; Geochronology; Geology; Lab

Ar-39 - Ar-40 Evidence for an Approximately 4.26 Ga Impact Heating Event on the LL Parent Body

NASA Technical Reports Server (NTRS)

Dixon, E. T.; Bogard, D. D.; Rubin, A. E.

2003-01-01

Miller Range 99301 is a type 6, unbrecciated LL chondrite. MIL 99301 is of interest because some compositional and petrographic features suggest it experienced rather high shock grades, whereas other features suggest it is relatively unshocked. Inconsistent shock indicators could be explained if MIL 99301 was shocked but then partly annealed by heat produced by impacts on the parent body. The hypothesis that MIL 99301 experienced high temperature metamorphism (type 6) followed by a later shock event that heated, but did not melt, the constituent feldspar can be evaluated using (39)Ar-(40)Ar chronology. This is because (39)Ar-(40)Ar ages of shocked ordinary chondrites are generally <4.2 Ga, whereas (39)Ar-(40)Ar ages of unshocked meteorites are generally older, and between 4.52 - 4.38 Ga.

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

PubMed

Zhang, Yajia; Pitchiaya, Sethuramasundaram; Cieślik, Marcin; Niknafs, Yashar S; Tien, Jean C-Y; Hosono, Yasuyuki; Iyer, Matthew K; Yazdani, Sahr; Subramaniam, Shruthi; Shukla, Sudhanshu K; Jiang, Xia; Wang, Lisha; Liu, Tzu-Ying; Uhl, Michael; Gawronski, Alexander R; Qiao, Yuanyuan; Xiao, Lanbo; Dhanasekaran, Saravana M; Juckette, Kristin M; Kunju, Lakshmi P; Cao, Xuhong; Patel, Utsav; Batish, Mona; Shukla, Girish C; Paulsen, Michelle T; Ljungman, Mats; Jiang, Hui; Mehra, Rohit; Backofen, Rolf; Sahinalp, Cenk S; Freier, Susan M; Watt, Andrew T; Guo, Shuling; Wei, John T; Feng, Felix Y; Malik, Rohit; Chinnaiyan, Arul M

2018-06-01

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

Aldose reductase mediates retinal microglia activation

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

Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu

Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migrationmore » in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.« less

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

PubMed

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-09-03

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

PubMed Central

O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

2014-01-01

Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: early hematological changes and systemic inflammatory response syndrome in minipig.

PubMed

Moroni, Maria; Elliott, Thomas B; Deutz, Nicolaas E; Olsen, Cara H; Owens, Rossitsa; Christensen, Christine; Lombardini, Eric D; Whitnall, Mark H

2014-05-01

To characterize acute radiation syndrome (ARS) sequelae at doses intermediate between the bone marrow (H-ARS) and full gastrointestinal (GI-ARS) syndrome. Male minipigs, approximately 5 months old, 9-12 kg in weight, were irradiated with Cobalt-60 (total body, bilateral gamma irradiation, 0.6 Gy/min). Endpoints were 10-day survival, gastrointestinal histology, plasma citrulline, bacterial translocation, vomiting, diarrhea, vital signs, systemic inflammatory response syndrome (SIRS), febrile neutropenia (FN). We exposed animals to doses (2.2-5.0 Gy) above those causing H-ARS (1.6-2.0 Gy), and evaluated development of ARS. Compared to what was observed during H-ARS (historical data: Moroni et al. 2011a , 2011c ), doses above 2 Gy produced signs of increasingly severe pulmonary damage, faster deterioration of clinical conditions, and faster increases in levels of C-reactive protein (CRP). In the range of 4.6-5.0 Gy, animals died by day 9-10; signs of the classic GI syndrome, as measured by diarrhea, vomiting and bacterial translocation, did not occur. At doses above 2 Gy we observed transient reduction in circulating citrulline levels, and animals exhibited earlier depletion of blood elements and faster onset of SIRS and FN. An accelerated hematopoietic subsyndrome (AH-ARS) is observed at radiation doses between those producing H-ARS and GI-ARS. It is characterized by early onset of SIRS and FN, and greater lung damage, compared to H-ARS.

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

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

Xu, Weihong; Xu, Bin; Yao, Yiting

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administrationmore » of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.« less

Photosynthetic and antioxidant responses of Liquidambar formosana and Schima superba seedlings to sulfuric-rich and nitric-rich simulated acid rain.

PubMed

Chen, Juan; Wang, Wen-Hua; Liu, Ting-Wu; Wu, Fei-Hua; Zheng, Hai-Lei

2013-03-01

To study whether differential responses occur in photosynthesis and antioxidant system for seedlings of Liquidambar formosana, an acid rain (AR)-sensitive tree species and Schima superba, an AR-tolerant tree species treated with three types of pH 3.0 simulated AR (SiAR) including sulfuric-rich (S-SiAR), nitric-rich (N-SiAR), sulfate and nitrate mixed (SN-SiAR), we investigated the changes of leaf necrosis, chlorophyll content, soluble protein and proline content, photosynthesis and chlorophyll fluorescence characteristics, reactive oxygen species production, membrane lipid peroxidation, small molecular antioxidant content, antioxidant enzyme activities and related protein expressions. Our results showed that SiAR significantly caused leaf necrosis, inhibited photosynthesis, induced superoxide radical and hydrogen peroxide generation, aggravated membrane lipid peroxidation, changed antioxidant enzyme activities, modified related protein expressions such as Cu/Zn superoxide dismutase (SOD), l-ascorbate peroxidase (APX, EC 1. 11. 1. 11), glutathione S transferase (GST, EC 2. 5. 1. 18) and Rubisco large subunit (RuBISCO LSU), altered non-protein thiols (NPT) and glutathione (GSH) content in leaves of L. formosana and S. superba. Taken together, we concluded that the damages caused by SiAR in L. formosana were more severe and suffered from more negative impacts than in S. superba. S-SiAR induced more serious damages for the plants than did SN-SiAR and N-SiAR. Crown Copyright © 2013. Published by Elsevier Masson SAS. All rights reserved.

Modeling Truncated AR Expression in a Natural Androgen Responsive Environment and Identification of RHOB as a Direct Transcriptional Target

PubMed Central

Tsai, Hui-Chi; Boucher, David L.; Martinez, Anthony; Tepper, Clifford G.; Kung, Hsing-Jien

2012-01-01

Recent studies identifying putative truncated androgen receptor isoforms with ligand-independent activity have shed new light on the acquisition of androgen depletion independent (ADI) growth of prostate cancer. In this study, we present a model system in which a C-terminally truncated variant of androgen receptor (TC-AR) is inducibly expressed in LNCaP, an androgen-dependent cell line, which expresses little truncated receptor. We observed that when TC-AR is overexpressed, the endogenous full length receptor (FL-AR) is transcriptionally downmodulated. This in essence allows us to “replace” FL-AR with TC-AR and compare their individual properties in exactly the same genetic and cellular background, which has not been performed before. We show that the TC-AR translocates to the nucleus, activates transcription of AR target genes in the absence of DHT and is sufficient to confer ADI growth to the normally androgen dependent LNCaP line. We also show that while there is significant overlap in the genes regulated by FL- and TC-AR there are also differences in the respective suites of target genes with each AR form regulating genes that the other does not. Among the genes uniquely activated by TC-AR is RHOB which is shown to be involved in the increased migration and morphological changes observed in LN/TC-AR, suggesting a role of RHOB in the regulation of androgen-independent behavior of prostate cancer cells. PMID:23209612

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism

PubMed Central

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-01-01

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression. PMID:27598153

Initial accomplishments of the Environmental Control and Life Support System (ECLSS) atmosphere revitalization (AR) predevelopment operational system test (POST) for the Space Station Freedom (SSF)

NASA Technical Reports Server (NTRS)

Dunn, Kevin H.; Bulgajewski, Peter J.

1992-01-01

Initial results of the integrated AR POST conducted by Boeing at Marshall Space Flight Center in 1992 are presented. The three baselined ECLSS Man Tended Capability AR assemblies were integrated and operated in a closed door chamber in which the internal atmosphere was monitored. The test provides a prerequisite checkout of the AR subsystem in preparation for longer duration tests in which the AR subsystem will be integrated with the Water Recovery Management subsystem. The integrated AR POST will serve as an early test bed to evaluate the integration of the space station ECLSS AR subsystem during design maturation.

Correlation of echo-Doppler aortic valve regurgitation index with angiographic aortic regurgitation severity.

PubMed

Chen, Ming; Luo, Huai; Miyamoto, Takashi; Atar, Shaul; Kobal, Sergio; Rahban, Masoud; Brasch, Andrea V; Makkar, Rajendra; Neuman, Yoram; Naqvi, Tasneem Z; Tolstrup, Kirsten; Siegel, Robert J

2003-09-01

We assessed aortic regurgitation (AR) severity by utilizing multiple echo-Doppler variables in comparison with AR severity by aortic root angiography. Patients were divided into 3 groups: mild, moderate, and severe. An AR index (ARI) was developed, comprising 5 echocardiographic parameters: ratio of color AR jet height to left ventricular outlet flow diameter, AR signal density from continuous-wave Doppler, pressure half-time, left ventricular end-diastolic diameter, and aortic root diameter. There was a strong correlation between AR severity by angiography and the calculated echo-Doppler ARI (r = 0.84, p = 0.0001). As validated by aortic angiography, the ARI is an accurate reflection of AR severity.

75 FR 38557 - Application Nos. and Proposed Exemptions; D-11489, Morgan Stanley & Co., Incorporated; L-11609...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

...; (b) The term ``Auction Rate Security'' or ``ARS'' means a security: (1) That is either a debt... Securities (ARS). The applicant describes ARS and the arrangement by which ARS are bought and sold as follows. ARS are securities (issued as debt or preferred stock) with an interest rate or dividend that is reset...

ACTH Action on StAR Biology

PubMed Central

Clark, Barbara J.

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

ACTH Action on StAR Biology.

PubMed

Clark, Barbara J

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

PubMed

Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

2015-02-01

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Voltammetric Response of Alizarin Red S-Confined Film-Coated Electrodes to Diol and Polyol Compounds: Use of Phenylboronic Acid-Modified Poly(ethyleneimine) as Film Component.

PubMed

Takahashi, Shigehiro; Suzuki, Iwao; Ojima, Takuto; Minaki, Daichi; Anzai, Jun-Ichi

2018-01-22

Alizarin red S (ARS) was confined in layer-by-layer (LbL) films composed of phenylboronic acid-modified poly(ethyleneimine) (PBA-PEI) and carboxymethylcellulose (CMC) to study the voltammetric response to diol and polyol compounds. The LbL film-coated gold (Au) electrode and quartz slide were immersed in an ARS solution to uptake ARS into the film. UV-visible absorption spectra of ARS-confined LbL film suggested that ARS formed boronate ester (ARS-PBS) in the film. The cyclic voltammetry of the ARS-confined LbL film-coated electrodes exhibited oxidation peaks at -0.50 and -0.62 V, which were ascribed to the oxidation reactions of ARS-PBS and free ARS, respectively, in the LbL film. The peak current at -0.62 V increased upon the addition of diol or polyol compounds such as L-dopa, glucose, and sorbitol into the solution, depending on the concentration, whereas the peak current at -0.50 V decreased. The results suggest a possible use of ARS-confined PBA-PEI/CMC LbL film-coated Au electrodes for the construction of voltammetric sensors for diol and polyol compounds.

Androgen Receptor (AR) in Cardiovascular Diseases

PubMed Central

Huang, Chiung-Kuei; Lee, Soo Ok; Chang, Eugene; Pang, Haiyan; Chang, Chawnshang

2016-01-01

Cardiovascular diseases (CVDs) are still the highest leading cause of death worldwide. Several risk factors have been linked to CVDs, including smoking, diabetes, hyperlipidemia, and gender among others. Sex hormones, especially the androgen and its receptor, androgen receptor (AR), have been linked to many diseases with a clear gender difference. Here, we summarize androgen/AR effects on CVDs, including hypertension, stroke, atherosclerosis, abdominal aortic aneurysm (AAA), myocardial hypertrophy, and heart failure, as well as metabolic syndrome/diabetes and their impacts on CVDs. Androgen/AR signaling exacerbates hypertension and anti-androgens may suppress hypertension. Androgen/AR signaling plays dual roles in strokes, depending on different kinds of factors, but generally males have a higher incidence of strokes than females. Androgen and AR differentially modulate atherosclerosis. Androgen deficiency causes elevated lipid accumulation to enhance atherosclerosis, but targeting AR in selective cells without altering serum androgen levels would suppress atherosclerosis progression. Androgen/AR signaling is crucial in AAA development and progression, and targeting androgen/AR profoundly restricts AAA progression. Men have increased cardiac hypertrophy as compared to age-matched women that may be due to androgens. Finally, androgen/AR plays important roles in contributing to obesity and insulin/leptin resistance to increase the metabolic syndrome. PMID:26769913

Effects of alkylresorcinols on volume and structure of yeast-leavened bread.

PubMed

Andersson, Annica Am; Landberg, Rikard; Söderman, Thomas; Hedkvist, Sofie; Katina, Kati; Juvonen, Riikka; Holopainen, Ulla; Lehtinen, Pekka; Aman, Per

2011-01-30

Alkylresorcinols (AR) are amphiphilic phenolic compounds found in high amounts in wheat, durum wheat and rye, with different homologue composition for each cereal. The effect of different amounts of added AR from these cereals on bread volume, height, porosity and microstructure was studied. Breads with added rye bran (with high levels of AR) or acetone-extracted rye bran (with low levels of AR) were also baked, as well as breads with finely milled forms of each of these brans. Breads with high amounts of added AR, irrespective of AR homologue composition, had a lower volume, a more compact structure and an adverse microstructure compared with breads with no or low levels of added AR. AR were also shown to inhibit the activity of baker's yeast. There was no difference in bread volume and porosity between bread baked with rye bran and acetone-extracted rye bran or with brans of different particle size. Irrespective of homologue composition, AR had a negative effect on wheat bread properties when added in high amounts as purified extracts from wheat, durum wheat and rye. Natural levels of AR in rye bran, however, did not affect the volume and porosity of yeast-leavened wheat breads. 2010 Society of Chemical Industry.

40Ar/39Ar and K-Ar data bearing on the metamorphic and tectonic history of western New England.

USGS Publications Warehouse

Sutter, J.F.; Ratcliffe, N.M.; Mukasa, S.B.

1985-01-01

40Ar/39Ar ages of coexisting biotite and hornblende from Proterozoic Y gneisses of the Berkshire and Green Mt massifs, as well as 40Ar/39Ar and K/Ar mineral and whole-rock ages from Palaeozoic metamorphic rocks, suggest that the thermal peaks for the dominant metamorphic recrystallization in western New England occurred 465 + or - 5 m.y. (Taconian). 40Ar/39Ar age data from a poorly-defined terrain along the eastern strip of the area suggests that the area has been retrograded during a metamorphism that peaked at least 376 + or - 5 m.y. (Acadian). Available age and petrological data from western New England indicate the presence of at least three separate metamorphic-structure domains of Taconic age: 1) a small area of relict high-P and low-T metamorphism, 2) a broad area of normal Barrovian metamorphism from chlorite to garnet grade characterized by a gentle metamorphic gradient and, 3) a rather narrow belt of steep-gradient, Barrovian series metamorphic rocks. Areas of maximum metamorphic intensity within the last domain coincide with areas of maximum crustal thickening in the later stage of Taconic orogeny. -L.di H

Antibiotic Resistome: Improving Detection and Quantification Accuracy for Comparative Metagenomics.

PubMed

Elbehery, Ali H A; Aziz, Ramy K; Siam, Rania

2016-04-01

The unprecedented rise of life-threatening antibiotic resistance (AR), combined with the unparalleled advances in DNA sequencing of genomes and metagenomes, has pushed the need for in silico detection of the resistance potential of clinical and environmental metagenomic samples through the quantification of AR genes (i.e., genes conferring antibiotic resistance). Therefore, determining an optimal methodology to quantitatively and accurately assess AR genes in a given environment is pivotal. Here, we optimized and improved existing AR detection methodologies from metagenomic datasets to properly consider AR-generating mutations in antibiotic target genes. Through comparative metagenomic analysis of previously published AR gene abundance in three publicly available metagenomes, we illustrate how mutation-generated resistance genes are either falsely assigned or neglected, which alters the detection and quantitation of the antibiotic resistome. In addition, we inspected factors influencing the outcome of AR gene quantification using metagenome simulation experiments, and identified that genome size, AR gene length, total number of metagenomics reads and selected sequencing platforms had pronounced effects on the level of detected AR. In conclusion, our proposed improvements in the current methodologies for accurate AR detection and resistome assessment show reliable results when tested on real and simulated metagenomic datasets.

Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.

PubMed

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-10-27

Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT.

Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity.

PubMed

Hornig, N C; Ukat, M; Schweikert, H U; Hiort, O; Werner, R; Drop, S L S; Cools, M; Hughes, I A; Audi, L; Ahmed, S F; Demiri, J; Rodens, P; Worch, L; Wehner, G; Kulle, A E; Dunstheimer, D; Müller-Roßberg, E; Reinehr, T; Hadidi, A T; Eckstein, A K; van der Horst, C; Seif, C; Siebert, R; Ammerpohl, O; Holterhus, P-M

2016-11-01

Only approximately 85% of patients with a clinical diagnosis complete androgen insensitivity syndrome and less than 30% with partial androgen insensitivity syndrome can be explained by inactivating mutations in the androgen receptor (AR) gene. The objective of the study was to clarify this discrepancy by in vitro determination of AR transcriptional activity in individuals with disorders of sex development (DSD) and male controls. Quantification of DHT-dependent transcriptional induction of the AR target gene apolipoprotein D (APOD) in cultured genital fibroblasts (GFs) (APOD assay) and next-generation sequencing of the complete coding and noncoding AR locus. The study was conducted at a university hospital endocrine research laboratory. GFs from 169 individuals were studied encompassing control males (n = 68), molecular defined DSD other than androgen insensitivity syndrome (AIS; n = 18), AR mutation-positive AIS (n = 37), and previously undiagnosed DSD including patients with a clinical suspicion of AIS (n = 46). There were no interventions. DHT-dependent APOD expression in cultured GF and AR mutation status in 169 individuals was measured. The APOD assay clearly separated control individuals (healthy males and molecular defined DSD patients other than AIS) from genetically proven AIS (cutoff < 2.3-fold APOD-induction; 100% sensitivity, 93.3% specificity, P < .0001). Of 46 DSD individuals with no AR mutation, 17 (37%) fell below the cutoff, indicating disrupted androgen signaling. AR mutation-positive AIS can be reliably identified by the APOD assay. Its combination with next-generation sequencing of the AR locus uncovered an AR mutation-negative, new class of androgen resistance, which we propose to name AIS type II. Our data support the existence of cellular components outside the AR affecting androgen signaling during sexual differentiation with high clinical relevance.

Coagulation factor VII is regulated by androgen receptor in breast cancer.

PubMed

Naderi, Ali

2015-02-01

Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

A NEW METHOD TO QUANTIFY AND REDUCE THE NET PROJECTION ERROR IN WHOLE-SOLAR-ACTIVE-REGION PARAMETERS MEASURED FROM VECTOR MAGNETOGRAMS

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

Falconer, David A.; Tiwari, Sanjiv K.; Moore, Ronald L.

Projection errors limit the use of vector magnetograms of active regions (ARs) far from the disk center. In this Letter, for ARs observed up to 60° from the disk center, we demonstrate a method for measuring and reducing the projection error in the magnitude of any whole-AR parameter that is derived from a vector magnetogram that has been deprojected to the disk center. The method assumes that the center-to-limb curve of the average of the parameter’s absolute values, measured from the disk passage of a large number of ARs and normalized to each AR’s absolute value of the parameter atmore » central meridian, gives the average fractional projection error at each radial distance from the disk center. To demonstrate the method, we use a large set of large-flux ARs and apply the method to a whole-AR parameter that is among the simplest to measure: whole-AR magnetic flux. We measure 30,845 SDO /Helioseismic and Magnetic Imager vector magnetograms covering the disk passage of 272 large-flux ARs, each having whole-AR flux >10{sup 22} Mx. We obtain the center-to-limb radial-distance run of the average projection error in measured whole-AR flux from a Chebyshev fit to the radial-distance plot of the 30,845 normalized measured values. The average projection error in the measured whole-AR flux of an AR at a given radial distance is removed by multiplying the measured flux by the correction factor given by the fit. The correction is important for both the study of the evolution of ARs and for improving the accuracy of forecasts of an AR’s major flare/coronal mass ejection productivity.« less

Coral calcifying fluid aragonite saturation states derived from Raman spectroscopy

NASA Astrophysics Data System (ADS)

DeCarlo, Thomas M.; D'Olivo, Juan P.; Foster, Taryn; Holcomb, Michael; Becker, Thomas; McCulloch, Malcolm T.

2017-11-01

Quantifying the saturation state of aragonite (ΩAr) within the calcifying fluid of corals is critical for understanding their biomineralization process and sensitivity to environmental changes including ocean acidification. Recent advances in microscopy, microprobes, and isotope geochemistry enable the determination of calcifying fluid pH and [CO32-], but direct quantification of ΩAr (where ΩAr = [CO32-][Ca2+]/Ksp) has proved elusive. Here we test a new technique for deriving ΩAr based on Raman spectroscopy. First, we analysed abiogenic aragonite crystals precipitated under a range of ΩAr from 10 to 34, and we found a strong dependence of Raman peak width on ΩAr with no significant effects of other factors including pH, Mg/Ca partitioning, and temperature. Validation of our Raman technique for corals is difficult because there are presently no direct measurements of calcifying fluid ΩAr available for comparison. However, Raman analysis of the international coral standard JCp-1 produced ΩAr of 12.3 ± 0.3, which we demonstrate is consistent with published skeletal Mg/Ca, Sr/Ca, B/Ca, δ11B, and δ44Ca data. Raman measurements are rapid ( ≤ 1 s), high-resolution ( ≤ 1 µm), precise (derived ΩAr ± 1 to 2 per spectrum depending on instrument configuration), accurate ( ±2 if ΩAr < 20), and require minimal sample preparation, making the technique well suited for testing the sensitivity of coral calcifying fluid ΩAr to ocean acidification and warming using samples from natural and laboratory settings. To demonstrate this, we also show a high-resolution time series of ΩAr over multiple years of growth in a Porites skeleton from the Great Barrier Reef, and we evaluate the response of ΩAr in juvenile Acropora cultured under elevated CO2 and temperature.

Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein.

PubMed

Steely, Andrea M; Willoughby, Jamin A; Sundar, Shyam N; Aivaliotis, Vasiliki I; Firestone, Gary L

2017-10-01

Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR. Furthermore, artemisinin stimulated AR ubiquitination and AR receptor interactions with the E3 ubiquitin ligase MDM2 in LNCaP cells. The artemisinin-induced loss of AR protein prevented androgen-responsive cell proliferation and ablated total AR transcriptional activity. The serine/threonine protein kinase AKT-1 was shown to be highly associated with artemisinin-induced proteasome-mediated degradation of AR protein. Artemisinin treatment activated AKT-1 enzymatic activity, enhanced receptor association with AKT-1, and induced AR serine phosphorylation. Treatment of LNCaP cells with the PI3-kinase inhibitor LY294002, which inhibits the PI3-kinase-dependent activation of AKT-1, prevented the artemisinin-induced AR degradation. Furthermore, in transfected receptor-negative PC-3 cells, artemisinin failed to stimulate the degradation of an altered receptor protein (S215A/S792A) with mutations in its two consensus AKT-1 serine phosphorylation sites. Taken together, our results indicate that artemisinin induces the degradation of AR protein and disrupts androgen responsiveness of human prostate cancer cells, suggesting that this natural compound represents a new potential therapeutic molecule that selectively targets AR levels.

The Development of Adultoid Reproductives and Brachypterous Neotenic Reproductives From the Last Instar Nymphs in Reticulitermes labralis (Isoptera: Rhinotermitidae): A Comparative Study

PubMed Central

Su, Xiao Hong; Xue, Wei; Liu, He; Chen, Jiao Ling; Zhang, Xiao Jing; Xing, Lian Xi; Liu, Ming Hua

2015-01-01

Secondary reproductives develop primarily from nymphs. However, they have been rarely studied; in particular, the development of adultoid reproductives (AR) with floppy wings is still unclear. In this study, the change in juvenile hormone (JH) levels, vitellogenin gene expression, and oogenesis during the development of AR and brachypterous neotenic reproductives (BN) from the last instar nymphs of Reticulitermes labralis are investigated and compared. The results showed that the AR derived from the last instar nymphs by molting, and they were more similar to neotenic reproductives in morphology. In addition, the paired AR were not able to survive in the absence of workers. In R. labralis, the process of the last instar nymphs developing into AR and BN took an increase in JH level as a starting point. The JH level of the last instar nymphs molting into BN was approximately 1.5-fold higher than that of the AR. Additionally, The JHIII level of BN peaked on day 5, and that of AR peaked on day 10, which induced the onset of vitellogenesis in BN and AR, respectively. After molting, the vitellogenin gene expression levels of both BN and AR initially increased and then declined, and the expression levels in the BN were significantly higher than those in the AR. In addition, the oocytes of BN matured earlier than those of the AR, and the number of eggs laid by the BN was higher than the number laid by the AR. Our results demonstrate that, in R. labralis, the last instar nymphs can develop into AR, which are significantly different from BN in their development. PMID:26494776

Dhofar 378 Martian shergottite: Evidence of early shock melting

NASA Astrophysics Data System (ADS)

Park, Jisun; Bogard, Donald D.; Mikouchi, Takashi; McKay, Gordon A.

2008-08-01

Shock heating of the Dhofar 378 (Dho 378) Martian shergottite produced melting, vesiculation, and flow of the plagioclase, which upon cooling recrystallized into complex textures. Heating experiments on the similar Zagami shergottite indicate that Dho 378 was shock heated to 1000-1100°C and was cooled at ~2.5°C/h. An 39Ar-40Ar analysis of Dho 378 plagioclase indicates different Ar diffusion domains and K/Ca ratios. The lower-temperature phase defines an Ar-Ar isochron age of 141 +/- 32 Ma. The higher-temperature phase released more 40Ar but does not define an age. The meteorite's thermal history was examined by constructing a generic model to compare cooling rates for objects of different sizes against fractional diffusion loss of Ar for different cooling times. Using gas diffusion parameter values measured for Dho 378, this model indicates that it is improbable that the major shock heating event occurred at the time that Dho 378 was ejected from Mars ~3 Ma ago. Rather, we suggest that the time of shock heating is probably given by its Ar-Ar age. For Dho 378 to cool sufficiently fast not to lose most of its 40Ar ~3 Ma ago would require it to have been ejected into space as an impossibly small object. Larger and more reasonable Mars ejection sizes indicate that Dho 378 should have lost most of its 40Ar. On the basis of plagioclase texture and Ar data, we suggest that a major impact event ~141 Ma ago melted Dho 378 plagioclase, degassed most of its 40Ar, and deposited it in crater ejecta to cool. A smaller and later impact ejected it into space ~3 Ma ago.

Intestinal Microbial Variation May Predict Early Acute Rejection after Liver Transplantation in Rats

PubMed Central

Ren, Zhigang; Jiang, Jianwen; Lu, Haifeng; Chen, Xinhua; He, Yong; Zhang, Hua; Xie, Haiyang; Wang, Weilin; Zheng, Shusen; Zhou, Lin

2014-01-01

Background Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT. Methods The OLT models in rats were established. Hepatic graft histology, ultrastructure, function, and intestinal barrier function were tested. Ileocecal contents were collected for intestinal microbial analysis. Results Hepatic graft suffered from the ischemia-reperfusion (I/R) injury on day 1, initial AR on day 3, and severe AR on day 7 after OLT. Real-time quantitative polymerase chain reaction results showed that genus Faecalibacterium prausnitzii and Lactobacillus were decreased, whereas Clostridium bolteae was increased during AR. Notably, cluster analysis of denaturing gradient gel electrophoresis (DGGE) profiles showed the 7AR and 3AR groups clustered together with 73.4% similarity, suggesting that intestinal microbiota was more sensitive than hepatic function in responding to AR. Microbial diversity and species richness were decreased during AR. Phylogenetic tree analysis showed that most of the decreased key bacteria belonged to phylum Firmicutes, whereas increased key bacteria belonged to phylum Bacteroidetes. Moreover, intestinal microvilli loss and tight junction damage were noted, and intestinal barrier dysfunction during AR presented a decrease of fecal secretory immunoglobulin A (sIgA) and increase of blood bacteremia, endotoxin, and tumor necrosis factor-α. Conclusion We dynamically detail intestinal microbial characterization and find a high sensitivity of microbial change during AR after OLT, suggesting that intestinal microbial variation may predict AR in early phase and become an assistant therapeutic target to improve rejection after OLT. PMID:25321166

Atmospheric Rivers in VR-CESM: Historical Comparison and Future Projections

NASA Astrophysics Data System (ADS)

McClenny, E. E.; Ullrich, P. A.

2016-12-01

Atmospheric rivers (ARs) are responsible for most of the horizontal vapor transport from the tropics, and bring upwards of half the annual precipitation to midlatitude west coasts. The difference between a drought year and a wet year can come down to 1-2 ARs. Such few events transform an otherwise arid region into one which supports remarkable biodiversity, productive agriculture, and booming human populations. It follows that such a sensitive hydroclimate feature would demand priority in evaluating end-of-century climate runs, and indeed, the AR subfield has grown significantly over the last decade. However, results tend to vary wildly from study to study, raising questions about how to best approach ARs in models. The disparity may result from any number of issues, including the ability for a model to properly resolve a precipitating AR, to the formulation and application of an AR detection algorithm. ARs pose a unique problem in global climate models (GCMs) computationally and physically, because the GCM horizontal grid must be fine enough to resolve coastal mountain range topography and force orographic precipitation. Thus far, most end-of-century projections on ARs have been performed on models whose grids are too coarse to resolve mountain ranges, causing authors to draw conclusions on AR intensity from water vapor content or transport alone. The use of localized grid refinement in the Variable Resolution version of NCAR's Community Earth System Model (VR-CESM) has succeeded in resolving AR landfall. This study applies an integrated water vapor AR detection algorithm to historical and future projections from VR-CESM, with historical ARs validated against NASA's Modern Era Retrospective-Analysis for Research and Applications. Results on end-of-century precipitating AR frequency, intensity, and landfall location will be discussed.

Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2-8) in Normal and Cancerous Breast and Prostate Cells.

PubMed

Hu, Dong Gui; McKinnon, Ross A; Hulin, Julie-Ann; Mackenzie, Peter I; Meech, Robyn

2016-12-27

Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2-8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer ( PCGEM1 , PEG3 , EPHA3 , and EFNB2 ) or other types of human cancers ( TOX3 , ST8SIA4 , and SLITRK3 ), and genes that are diagnostic/prognostic biomarkers of prostate cancer ( GRINA3 , and BCHE ).

Androgen receptor polyglutamine repeat length (AR-CAGn) modulates the effect of testosterone on androgen-associated somatic traits in Filipino young adult men.

PubMed

Ryan, Calen P; Georgiev, Alexander V; McDade, Thomas W; Gettler, Lee T; Eisenberg, Dan T A; Rzhetskaya, Margarita; Agustin, Sonny S; Hayes, M Geoffrey; Kuzawa, Christopher W

2017-06-01

The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels. We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines (n = 675). When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn (p < .1), consistent with in vitro research. However, when waking T was high, we observed the opposite effect-lengthening AR-CAGn was associated with an increase in these same somatic traits. Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations. © 2017 Wiley Periodicals, Inc.

AR Signaling in Breast Cancer.

PubMed

Rahim, Bilal; O'Regan, Ruth

2017-02-24

Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies.

A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer.

PubMed

Liu, Xichun; Ledet, Elisa; Li, Dongying; Dotiwala, Ary; Steinberger, Allie; Feibus, Allison; Li, Jianzhuo; Qi, Yanfeng; Silberstein, Jonathan; Lee, Benjamin; Dong, Yan; Sartor, Oliver; Zhang, Haitao

2016-12-01

Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR (androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients. Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction. Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and AR v567es were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies. To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

AR Signaling in Breast Cancer

PubMed Central

Rahim, Bilal; O’Regan, Ruth

2017-01-01

Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies. PMID:28245550

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer.

PubMed

Park, Sang Eun; Kim, Ha-Gyeong; Kim, Dong Eun; Jung, Yoo Jung; Kim, Yunlim; Jeong, Seong-Yun; Choi, Eun Kyung; Hwang, Jung Jin; Kim, Choung-Soo

2018-04-01

Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting. The nuclear localization of AR was examined via immunocytochemical staining in 22Rv1 cells and primary tumor cells from a patient with CRPC. Results Combination treatment with HDACIs (vorinostat or CG200745) and docetaxel synergistically inhibited the growth of 22Rv1 and VCaP cells. Consistently, the combination treatment decreased the levels of full-length AR (AR-FL), AR splice variants (AR-Vs), prostate-specific antigen (PSA), and anti-apoptotic Bcl-2 proteins more efficiently compared with docetaxel or vorinostat alone. Moreover, the combination treatment accelerated the acetylation and bundling of tubulin, which significantly inhibited the nuclear accumulation of AR in 22Rv1 cells. The cytoplasmic colocalization of AR-FL and AR-V7 with microtubule bundles increased after combination treatment in primary tumor cells from a patient with CRPC. Conclusions The results suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC.

Selective Gene Regulation by Androgen Receptor in Prostate Cancer

DTIC Science & Technology

2012-10-01

empty vector, wt AR, AR-E255K and AR- R753Q cells were transfected with an ARE- responsive reporter and renilla as control. Cells were treated with...empty vector (empty), wild-type AR (WT), AR-E255K or AR-R753Q were transfected with ARE-luciferase and renilla . Cells were treated with 0 or 1 nm...R1881, harvested after 24 hrs to read luciferase and renilla actiivity. % G ro w th (D ay 5 / D ay 1 ) Vector WTAR E255KR753Q 600 700 800 900

Noninvasive Detection of AR-FL/AR V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration-Resistant Prostate Cancer

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-2-0050 TITLE: Noninvasive Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in Men with...report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated...Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration-Resistant Prostate Cancer 5c. PROGRAM

Noninvasive Detection of AR-FL/AR-V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration-Resistant Prostate Cancer

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-2-0052 TITLE: Noninvasive Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in Men with...DISTRIBUTION STATEMENT: Distribution Statement A: unlimited distribution The views, opinions and/or findings contained in this report are those of the...COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE Noninvasive Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in

Noninvasive Detection of AR-FL/AR-V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration-Resistant Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-2-0050 TITLE: Noninvasive Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in Men with...report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...Detection of AR -FL/ AR -V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration- Resistant Prostate Cancer 5c. PROGRAM

Constraints on Earth degassing history from the argon isotope composition of Devonian atmosphere

NASA Astrophysics Data System (ADS)

Stuart, F. M.; Mark, D.

2012-04-01

The primordial and radiogenic isotopes of the noble gases combine to make them a powerful tool for determining the time and tempo of the outgassing of the Earth's interior. The outgassing history of the Earth is largely constrained from measurements of the isotopic composition of He, Ne, Ar and Xe in samples of modern mantle, crust and atmosphere. There have been few unequivocal measurement of the isotopic composition of noble gases in ancient atmosphere. We have re-visited whether ancient Ar is trapped in the ~400 Ma Rhynie chert [1]. We have analysed samples of pristine Rhynie chert using the ARGUS multi-collector mass spectrometer calibrated against the new determination of atmospheric Ar isotope ratios [2]. 40Ar/36Ar ratios are low, with many lower than the modern air value (298.8). Importantly these are accompanied by atmospheric 38Ar/36Ar ratios indicating that the low 40Ar/36Ar are not due to mass fractionation. We conclude that the Rhynie chert has captured Devonian atmosphere-derived Ar. The data indicate that the Devonian atmosphere 40Ar/36Ar was at least 3 % lower than the modern air value. Thus the Earth's atmosphere has accumulated at least 5 ± 0.2 x 1016 moles of 40Ar in the last 400 million years, at an average rate of 1.24 ± 0.06 x 108 mol 40Ar/year. This overlaps the rate determined from ice cores for the last 800,000 years [3] and implies that there has been no resolvable temporal change in Earth outgassing rate since mid-Palaeozoic times. The new data require the Earth outgassed early, and suggests that pristine samples of Archaean and Proterozoic chert may prove useful as palaeo-atmosphere tracers. [1] G. Turner, J. Geol. Soc. London 146, 147-154 (1989) [2] D. Mark, F.M. Stuart, M. de Podesta, Geochim. Cosmochim. Acta 75, 7494-7501 [3] M. Bender et al., Proc. Nat. Acad. Sci. 105, 8232-8237 (2008)

Differential unroofing within the central metasedimentary Belt of the Grenville Orogen: constraints from 40Ar/39Ar thermochronology

USGS Publications Warehouse

Cosca, M.A.; Essene, E.J.; Kunk, Michael J.; Sutter, J.F.

1992-01-01

An 40Ar/39Ar thermochronological investigation of upper greenschist to granulite facies gneiss, amphibolite and marble was conducted in the Central Metasedimentary Belt (CMB), Ontario, to constrain its cooling history. Incremental 40Ar/39Ar release spectra indicate that substantial differential unroofing occurred in the CMB between ??? 1000 and ??? 600 Ma. A consistent pattern of significantly older hornblende and phlogopite 40Ar/3Ar cooling ages on the southeast sides of major northeast striking shear zones is interpreted to reflect late displacement due to extensional deformation. Variations in hornblende 40Ar/39Ar age plateaus exceeding 200 Ma occur over distances less than 50 km with major age discontinuities occurring across the Robertson Lake shear zone and the Sharbot Lake mylonite zone which separate the Sharbot Lake terrane from the Elzevir and Frontenac terranes. Extensional displacements of up to 14 km are inferred between the Frontenac and Elzevir terranes of the CMB. No evidence for significant post argon-closure vertical displacement is indicated in the vicinity of the Perth Road mylonite within the Frontenac terrane. Variations of nearly 100 Ma in phlogopite 40Ar/39Ar plateau ages occur in undeformed marble on either side of the Bancroft Shear Zone. Phlogopites from sheared and mylonitized marble within the shear zone yield 40Ar/39Ar diffusional loss profiles, but have older geologically meaningless ages thought to reflect incorporation of excess argon. By ??? 900 Ma, southeast directed extension was occurring throughout the CMB, possibly initiated along previous zones of compressional shearing. An easterly migration of active zones of extension is inferred, possibly related to an earlier, overall easterly migration of active zones of regional thrusting and easterly migration of an ancient subduction zone. The duration of extensional shearing is not well constrained, but must have ceased before ??? 600 Ma as required by the deposition of overlying undeformed Cambrian and/or Ordovician sedimentary rocks. ?? 1992 Springer-Verlag.

Expectations for methodology and translation of animal research: a survey of health care workers.

PubMed

Joffe, Ari R; Bara, Meredith; Anton, Natalie; Nobis, Nathan

2015-05-07

Health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR); therefore, an awareness of the empirical costs and benefits of animal research is an important issue for HCW. We aim to determine what health-care-workers consider should be acceptable standards of AR methodology and translation rate to humans. After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory-therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, methodology of AR, and expectations from AR. Responses of pediatricians and nurses/RTs were compared using Chi-square, with P < .05 considered significant. Response rate was 44/114(39%) (pediatricians), and 69/120 (58%) (nurses/RTs). Asked about methodological quality, most respondents expect that: AR is done to high quality; costs and difficulty are not acceptable justifications for low quality; findings should be reproducible between laboratories and strains of the same species; and guidelines for AR funded with public money should be consistent with these expectations. Asked about benefits of AR, most thought that there are sometimes/often large benefits to humans from AR, and disagreed that "AR rarely produces benefit to humans." Asked about expectations of translation to humans (of toxicity, carcinogenicity, teratogenicity, and treatment findings), most: expect translation >40% of the time; thought that misleading AR results should occur <21% of the time; and that if translation was to occur <20% of the time, they would be less supportive of AR. There were few differences between pediatricians and nurses/RTs. HCW have high expectations for the methodological quality of, and the translation rate to humans of findings from AR. These expectations are higher than the empirical data show having been achieved. Unless these areas of AR significantly improve, HCW support of AR may be tenuous.

Mechanistic Study on Cu(II)-Catalyzed Oxidative Cross-Coupling Reaction between Arenes and Boronic Acids under Aerobic Conditions.

PubMed

Zhang, Qian; Liu, Yang; Wang, Ting; Zhang, Xinhao; Long, Chao; Wu, Yun-Dong; Wang, Mei-Xiang

2018-04-25

Substantial attention has been given to modern organocopper chemistry in recent years since copper salts are naturally abundant, cheap, and less toxic in comparison to precious metals. Copper salts also exhibit versatility in catalyzing and mediating carbon-carbon and carbon-heteroatom bond forming reactions. Despite the wide applications of copper salts in catalysis, reaction mechanisms have remained elusive. Using azacalix[1]arene[3]pyridine, an arene-embedded macrocycle, and its isolated and structurally well-defined ArCu(II) and ArCu(III) compounds as molecular tools, we now report an in-depth experimental and computational study on the mechanism of a Cu(II)-catalyzed oxidative cross-coupling reaction between arenes and boronic acids with air as the oxidant. Stoichiometric reaction of organocopper compounds with p-tolylboronic acid validated arylcopper(II) rather than arylcopper(III) as a reactive organometallic intermediate. XPS, EPR, 1 H NMR, HRMS, and UV-vis spectroscopic evidence along with the isolation and quantification of all products and copper speciation, combined with computational analysis of the electronic structure and energetics of the transient intermediates, suggested a reaction sequence involving electrophilic metalation of arene by Cu(II), transmetalation of arylboronate to ArCu(II), the redox reaction between the resulting ArCu(II)Ar' and ArCu(II) to form respectively ArCu(III)Ar' and ArCu(I), and finally reductive elimination of ArCu(III)Ar'. Under aerobic catalytic conditions, all Cu(I) ions released from reductive elimination of ArCu(III)Ar' and from protolysis of ArCu(I) were oxidized by oxygen to regenerate Cu(II) species that enters into the next catalytic cycle. The unraveled reactivity of arylcopper(II) compounds and the catalytic cycle would enrich our knowledge of modern organocopper chemistry and provide useful information in the design of copper-catalyzed reactions.

Arsenic biotransformation potential of microbial arsH responses in the biogeochemical cycling of arsenic-contaminated groundwater.

PubMed

Chang, Jin-Soo; Yoon, In-Ho; Kim, Kyoung-Woong

2018-01-01

ArsH encodes an oxidoreductase, an NAD(P)H-dependent mononucleotide reductase, with an unknown function, frequently within an ars operon, and is widely distributed in bacteria. Novel arsenite-oxidizing bacteria have been isolated from arsenic-contaminated groundwater and surface soil in Vietnam. We found that ArsH gene activity, with arsenite oxidase in the periplasm; it revealed arsenic oxidation potential of the arsH system. Batch experiment results revealed Citrobacter freundii strain VTan4 (DQ481466) and Pseudomonas putida strain VTw33 (DQ481482) completely oxidized 1 mM of arsenite to arsenate within 30-50 h. High concentrations of arsenic were detected in groundwater and surrounding soil obtained from Vinh Tru village in Ha Nam province (groundwater: 11.0 μg/L to 37.0 μg/L; and soil: 2.5 mg/kg, 390.1 mg/kg), respectively. An arsH gene encoding an organoarsenical oxidase protein was observed in arsenite-oxidizing Citrobacter freundii strain VTan4 (DQ481466), whereas arsB, arsH, and arsH were detected in Pseudomonas putida strain VTw33 (DQ481482). arsH gene in bacteria was first reported from Vietnam for resistance and arsenite oxidase. We proposed that residues, Ser 43, Arg 45, Ser 48, and Tyr 49 are required for arsenic binding and activation of arsH. The ars-mediated biotransformation strongly influenced potential arsenite oxidase enzyme of the operon encoding a homogeneous arsH. Results suggest that the further study of arsenite-oxidizing bacteria may lead to a better understanding of arsenite oxidase responses, such as those of arsH, that may be applied to control biochemical properties; for example, speciation, detoxification, bioremediation, biotransformation, and mobilization of arsenic in contaminated groundwater. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

PubMed

Xiong, Yaoyao; Wang, Long; Li, Yuan; Chen, Minfeng; He, Wei; Qi, Lin

2017-01-01

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation. © 2017 The Author(s). Published by S. Karger AG, Basel.

CgA1AR-1 acts as an alpha-1 adrenergic receptor in oyster Crassostrea gigas mediating both cellular and humoral immune response.

PubMed

Liu, Zhaoqun; Zhou, Zhi; Wang, Lingling; Qiu, Limei; Zhang, Huan; Wang, Hao; Song, Linsheng

2016-11-01

We have now cloned an alpha-1 adrenergic receptor (A1AR) from the cDNA library of oyster Crassostrea gigas, designating as CgA1AR-1. The full length of CgA1AR-1 was 1149 bp and it encodes a protein of 382 amino acids containing a 7 transmembrane domain, whose putative topology was similar to the A1ARs in higher organisms and shared similarity of 19% with mammalian A1ARs according to the phylogenic analysis. After cell transfection of CgA1AR-1 into HEK293T cells and the incubation with its specific agonist norepinephrine (NE), the concentration of second messenger Ca 2+ increased significantly (p < 0.05). But, this increasing of Ca 2+ could be inhibited by adding A1AR antagonist DOX. Tissue distribution assays using qRT-PCR suggested that CgA1AR-1 mRNA was ubiquitously expressed in all the major tissues of oyster. LPS stimulation could induce the up-regulation of CgA1AR-1 mRNA in haemocytes from 12 h to 24 h post stimulation. Moreover, the blocking of CgA1AR-1 by DOX before LPS stimulation affected the mRNA expression of oyster TNF (CGI_10005109 and CGI_10006440) in haemocytes, resulting in the rise of haemocyte phagocytic rate and apoptosis index. In addition to cellular immunity, CgA1AR-1 was also involved in humoral immunity of oyster. Inhibition of CgA1AR-1 with DOX could repress the up-regulation of LZY and SOD activities caused by LPS stimulation. These results suggested that CgA1AR-1 acted as an α-1 adrenergic receptor in cetacholaminergic neuroendocrine-immune network mediating both cellular and humoral immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Branched Chain RNA In Situ Hybridization for Androgen Receptor Splice Variant AR-V7 as a Prognostic Biomarker for Metastatic Castration-Sensitive Prostate Cancer.

PubMed

Saylor, Philip J; Lee, Richard J; Arora, Kshitij S; Deshpande, Vikram; Hu, Rong; Olivier, Kara; Meneely, Erika; Rivera, Miguel N; Ting, David T; Wu, Chin-Lee; Miyamoto, David T

2017-01-15

The androgen receptor (AR) mRNA splice variant AR-V7 has emerged as a predictive biomarker for response to AR-targeted therapies. There are currently no commercially available assays to detect AR splice variants. The branched chain RNA in situ hybridization (ISH) platform enables the highly sensitive detection of RNA transcripts in formalin-fixed, paraffin-embedded (FFPE) tissues. We designed a branched chain RNA ISH probe to target the unique cryptic exon CE3 of AR-V7 using multiple tiling probes. This automated ISH assay was applied to tumor tissue from two distinct clinical cohorts that we hypothesized would differ in AR-V7 status. We detected AR-V7 in all tumor samples from men with metastatic castration-resistant prostate cancer with tissue obtained after disease progression despite at least one subsequent line of hormonal therapy (abiraterone, enzalutamide, or bicalutamide; n = 12). We detected AR-V7 in just one tumor from men who had undergone prostatectomy for localized adenocarcinoma (n = 30; Gleason 4 + 5 = 9 in the AR-V7-positive sample). Given the apparent distinction between the above groups by AR-V7 signal, we analyzed pretreatment AR-V7 status as a predictive and prognostic biomarker in men with treatment-naïve metastatic disease. Patients with metastases but without detectable AR-V7 RNA at baseline had significantly longer overall survival (log-rank P = 0.044) and a trend toward superior progression-free survival (log-rank P = 0.055). Within an institutional cohort, the RNA ISH assay identified AR-V7 within FFPE tissue and may have prognostic value in metastatic castration-sensitive prostate cancer. These preliminary findings warrant further study in larger cohorts. Clin Cancer Res; 23(2); 363-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth.

PubMed

Deng, X; Shao, G; Zhang, H-T; Li, C; Zhang, D; Cheng, L; Elzey, B D; Pili, R; Ratliff, T L; Huang, J; Hu, C-D

2017-03-02

Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells. Knockdown of PRMT5 or inhibition of PRMT5 by a specific inhibitor reduces the expression of AR and suppresses the growth of multiple AR-positive, but not AR-negative, prostate cancer cells. Significantly, knockdown of PRMT5 in AR-positive LNCaP cells completely suppresses the growth of xenograft tumors in mice. Molecular analysis reveals that PRMT5 binds to the proximal promoter region of the AR gene and contributes mainly to the enriched symmetric dimethylation of H4R3 in the same region. Mechanistically, PRMT5 is recruited to the AR promoter by its interaction with Sp1, the major transcription factor responsible for AR transcription, and forms a complex with Brg1, an ATP-dependent chromatin remodeler, on the proximal promoter region of the AR gene. Furthermore, PRMT5 expression in prostate cancer tissues is significantly higher than that in benign prostatic hyperplasia tissues, and PRMT5 expression correlates positively with AR expression at both the protein and mRNA levels. Taken together, our results identify PRMT5 as a novel epigenetic activator of AR in prostate cancer. Given that inhibiting AR transcriptional activity or androgen synthesis remains the major mechanism of action for most existing anti-androgen agents, our findings also raise an interesting possibility that targeting PRMT5 may represent a novel approach for prostate cancer treatment by eliminating AR expression.

An analysis of dormancy, ABA responsiveness, after-ripening and pre-harvest sprouting in hexaploid wheat (Triticum aestivum L.) caryopses.

PubMed

Gerjets, Tanja; Scholefield, Duncan; Foulkes, M John; Lenton, John R; Holdsworth, Michael J

2010-01-01

Embryo and caryopsis dormancy, abscisic acid (ABA) responsiveness, after-ripening (AR), and the disorder pre-harvest sprouting (PHS) were investigated in six genetically related wheat varieties previously characterized as resistant, intermediate, or susceptible to PHS. Timing of caryopsis AR differed between varieties; AR occurred before harvest ripeness in the most PHS-susceptible, whereas AR was slowest in the most PHS-resistant. Whole caryopses of all varieties showed little ABA-responsiveness during AR; PHS-susceptible varieties were responsive at the beginning of the AR period whereas PHS-resistant showed some responsiveness throughout. Isolated embryos showed relatively little dormancy during grain-filling and most varieties exhibited a window of decreased ABA-responsiveness around the period of maximum dry matter accumulation (physiological maturity). Susceptibility to PHS was assessed by overhead misting of either isolated ears or whole plants during AR; varieties were clearly distinguished using both methods. These analyses allowed an investigation of the interactions between the different components of seed development, compartments, and environment for the six varieties. There was no direct relationship between speed of caryopsis AR and embryo dormancy or ABA-responsiveness during seed maturation. However, the velocity of AR of a variety was closely associated with the degree of susceptibility to PHS during AR suggesting that these characters are developmentally linked. Investigation of genetic components of AR may therefore aid breeding approaches to reduce susceptibility to PHS.

Molecular identification of arsenic-resistant estuarine bacteria and characterization of their ars genotype.

PubMed

Sri Lakshmi Sunita, M; Prashant, S; Bramha Chari, P V; Nageswara Rao, S; Balaravi, Padma; Kavi Kishor, P B

2012-01-01

In the present study, 44 arsenic-resistant bacteria were isolated through serial dilutions on agar plate with concentrations ≥0.05 mM of sodium arsenite and ≥10 mM of sodium arsenate from Mandovi and Zuari--estuarine water systems. The ars genotype characterization in 36 bacterial isolates (resistant to 100 mM of sodium arsenate) revealed that only 17 isolates harboured the arsA (ATPase), B (arsenite permease) and C (arsenate reductase) genes on the plasmid DNA. The arsA, B and C genes were individually detected using PCR in 16, 9 and 13 bacterial isolates respectively. Molecular identification of the 17 isolates bearing the ars genotype was carried using 16S rDNA sequencing. A 1300 bp full length arsB gene encoding arsenite efflux pump and a 409 bp fragment of arsC gene coding for arsenate reductase were isolated from the genera Halomonas and Acinetobacter. Phylogenetic analysis of arsB and arsC genes indicated their close genetic relationship with plasmid borne ars genes of E. coli and arsenate reductase of plant origin. The putative arsenate reductase gene isolated from Acinetobacter species complemented arsenate resistance in E. coli WC3110 and JM109 validating its function. This study dealing with isolation of native arsenic-resistant bacteria and characterization of their ars genes might be useful to develop efficient arsenic detoxification strategies for arsenic contaminated aquifers.

Inhibition of androgen receptor and β-catenin activity in prostate cancer

PubMed Central

Lee, Eugine; Madar, Aviv; David, Gregory; Garabedian, Michael J.; DasGupta, Ramanuj; Logan, Susan K.

2013-01-01

Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective approach to treating prostate cancer. Here we provide proof-of-concept that a small-molecule inhibitor of nuclear β-catenin activity (called C3) can inhibit both the AR and β-catenin–signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both β-catenin/T-cell factor and β-catenin/AR protein interaction, reflecting the fact that T-cell factor and AR have overlapping binding sites on β-catenin. Given that AR interacts with, and is transcriptionally regulated by β-catenin, C3 treatment also resulted in decreased occupancy of β-catenin on the AR promoter and diminished AR and AR/β-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and β-catenin cofactor, coactivator-associated arginine methyltransferase 1 (CARM1), providing insight into the unrecognized function of β-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model and blocked renewal of bicalutamide-resistant sphere-forming cells, indicating the therapeutic potential of this approach. PMID:24019458

BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability

PubMed Central

Kuo, P-C; Huang, C-W; Lee, C-I; Chang, H-W; Hsieh, S-W; Chung, Y-P; Lee, M-S; Huang, C-S; Tsao, L-P; Tsao, Y-P; Chen, S-L

2015-01-01

Background: We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR. Methods: Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively. Results: BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome. Conclusions: In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa. PMID:25461807

ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells.

PubMed

Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H; Morton, Derrick J; Patel, Divya; Joshi, Jugal; Upadhyay, Sunil; Chaudhary, Jaideep

2016-09-09

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function. Copyright © 2016 Elsevier Inc. All rights reserved.

Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer

PubMed Central

Narizhneva, Natalia V.; Tararova, Natalia D.; Ryabokon, Petro; Shyshynova, Inna; Prokvolit, Anatoly; Komarov, Pavel G.; Purmal, Andrei A.; Gudkov, Andrei V.; Gurova, Katerina V.

2010-01-01

In prostate cancer (PCa) patients, initial responsiveness to androgen deprivation therapy is frequently followed by relapse due to development of treatment-resistant androgen-independent PCa. This is typically associated with acquisition of mutations in AR that allow activity as a transcription factor in the absence of ligand, indicating that androgen-independent PCa remains dependent on AR function. Our strategy to effectively target AR in androgen-independent PCa involved using a cell-based readout to isolate small molecules that inhibit AR transactivation function through mechanisms other than modulation of ligand binding. A number of the identified inhibitors were toxic to AR-expressing PCa cells regardless of their androgen dependence. Among these, some only suppressed PCa cell growth (ARTIS), while others induced cell death (ARTIK). ARTIK, but not ARTIS, compounds caused disappearance of AR protein from treated cells. siRNA against AR behaved like ARTIK compounds, while a dominant negative AR mutant that prevents AR-mediated transactivation but does not eliminate the protein showed only a growth suppressive effect. These observations reveal a transcription-independent function of AR that is essential for PCa cell viability and, therefore, is an ideal target for anti-PCa treatment. Indeed, several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization. PMID:19946220

Characterization of karyopherins in androgen receptor intracellular trafficking in the yeast model

PubMed Central

Nguyen, Minh M; Harmon, Robert M; Wang, Zhou

2014-01-01

Background: Mechanisms regulating androgen receptor (AR) subcellular localization represent an essential component of AR signaling. Karyopherins are a family of nucleocytoplasmic trafficking factors. In this paper, we used the yeast model to study the effects of karyopherins on the subcellular localization of the AR. Methods: Yeast mutants deficient in different nuclear transport factors were transformed with various AR based, GFP tagged constructs and their localization was monitored using microscopy. Results: We showed that yeast can mediate androgen-induced AR nuclear localization and that in addition to the import factor, Importinα/β, this process required the import karyopherin Sxm1. We also showed that a previously identified nuclear export sequence (NESAR) in the ligand binding domain of AR does not appear to rely on karyopherins for cytoplasmic localization. Conclusions: These results suggest that while AR nuclear import relies on karyopherin activity, AR nuclear export and/or cytoplasmic localization may require other undefined mechanisms. PMID:25031696

Sequence Complexity of Amyloidogenic Regions in Intrinsically Disordered Human Proteins

PubMed Central

Das, Swagata; Pal, Uttam; Das, Supriya; Bagga, Khyati; Roy, Anupam; Mrigwani, Arpita; Maiti, Nakul C.

2014-01-01

An amyloidogenic region (AR) in a protein sequence plays a significant role in protein aggregation and amyloid formation. We have investigated the sequence complexity of AR that is present in intrinsically disordered human proteins. More than 80% human proteins in the disordered protein databases (DisProt+IDEAL) contained one or more ARs. With decrease of protein disorder, AR content in the protein sequence was decreased. A probability density distribution analysis and discrete analysis of AR sequences showed that ∼8% residue in a protein sequence was in AR and the region was in average 8 residues long. The residues in the AR were high in sequence complexity and it seldom overlapped with low complexity regions (LCR), which was largely abundant in disorder proteins. The sequences in the AR showed mixed conformational adaptability towards α-helix, β-sheet/strand and coil conformations. PMID:24594841

Molecular modeling of the effects of 40Ar recoil in illite particles on their K-Ar isotope dating

NASA Astrophysics Data System (ADS)

Szczerba, Marek; Derkowski, Arkadiusz; Kalinichev, Andrey G.; Środoń, Jan

2015-06-01

The radioactive decay of 40K to 40Ar is the basis of isotope age determination of micaceous clay minerals formed during diagenesis. The difference in K-Ar ages between fine and coarse grained illite particles has been interpreted using detrital-authigenic components system, its crystallization history or post-crystallization diffusion. Yet another mechanism should also be considered: natural 40Ar recoil. Whether this recoil mechanism can result in a significant enough loss of 40Ar to provide observable decrease of K-Ar age of the finest illite crystallites at diagenetic temperatures - is the primary objective of this study which is based on molecular dynamics (MD) computer simulations. All the simulations were performed for the same kinetic energy (initial velocity) of the 40Ar atom, but for varying recoil angles that cover the entire range of their possible values. The results show that 40Ar recoil can lead to various deformations of the illite structure, often accompanied by the displacement of OH groups or breaking of the Si-O bonds. Depending on the recoil angle, there are four possible final positions of the 40Ar atom with respect to the 2:1 layer at the end of the simulation: it can remain in the interlayer space or end up in the closest tetrahedral, octahedral or the opposite tetrahedral sheet. No simulation angles were found for which the 40Ar atom after recoil passes completely through the 2:1 layer. The energy barrier for 40Ar passing through the hexagonal cavity from the tetrahedral sheet into the interlayer was calculated to be 17 kcal/mol. This reaction is strongly exothermic, therefore there is almost no possibility for 40Ar to remain in the tetrahedral sheet of the 2:1 layer over geological time periods. It will either leave the crystal, if close enough to the edge, or return to the interlayer space. On the other hand, if 40Ar ends up in the octahedral sheet after recoil, a substantially higher energy barrier of 55 kcal/mol prevents it from leaving the TOT layer over geological time. Based on the results of MD simulations, the estimates of the potential effect of 40Ar recoil on the K-Ar dating of illite show that some of 40Ar is lost and the loss is substantially dependent on the crystallite dimensions. The 40Ar loss can vary from 10% for the finest crystallites (two 2:1 layers thickness and <0.02 μm in diameter) to close to zero for the thickest and largest (in the ab plane) ones. Because the decrease of the K-Ar estimated age is approximately proportional to the 40Ar loss, the finer crystallites show lower apparent age than the coarser ones, although the age of crystallization is assumed equal for all the crystallites. From the model it is also clear that the lack of K removal from illite fringes (potentially Ar-free) strongly increases the apparent age differences among crystallites of different size.