DIVERGENT HORIZONTAL SUB-SURFACE FLOWS WITHIN ACTIVE REGION 11158

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

Jain, Kiran; Tripathy, S. C.; Hill, F., E-mail: kjain@nso.edu, E-mail: stripathy@nso.edu, E-mail: fhill@nso.edu

We measure the horizontal subsurface flow in a fast emerging active region (AR; NOAA 11158) using the ring-diagram technique and the Helioseismic and Magnetic Imager high spatial resolution Dopplergrams. This AR had a complex magnetic structure and displayed significant changes in morphology during its disk passage. Over a period of six days from 2011 February 11 to 16, the temporal variation in the magnitude of the total velocity is found to follow the trend of magnetic field strength. We further analyze regions of individual magnetic polarity within AR 11158 and find that the horizontal velocity components in these sub-regions havemore » significant variation with time and depth. The leading and trailing polarity regions move faster than the mixed-polarity region. Furthermore, both zonal and meridional components have opposite signs for trailing and leading polarity regions at all depths showing divergent flows within the AR. We also find a sharp decrease in the magnitude of total horizontal velocity in deeper layers around major flares. It is suggested that the re-organization of magnetic fields during flares, combined with the sunspot rotation, decreases the magnitude of horizontal flows or that the flow kinetic energy has been converted into the energy released by flares. After the decline in flare activity and sunspot rotation, the flows tend to follow the pattern of magnetic activity. We also observe less variation in the velocity components near the surface but these tend to increase with depth, further demonstrating that the deeper layers are more affected by the topology of ARs.« less

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.

α1- and α2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats.

PubMed

Oliveira, Luiz M; Moreira, Thiago S; Kuo, Fu-Shan; Mulkey, Daniel K; Takakura, Ana C

2016-09-01

Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by α1-/α2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate the sources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injecting the retrograde tracer Fluoro-Gold into the RTN, we identified back-labeled catecholaminergic neurons in the A7 region. In urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats unilateral injection of NE or moxonidine (α2-AR agonist) blunted diaphragm muscle activity (DiaEMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (α2-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (α1-AR agonist) increased DiaEMG amplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (α1-AR antagonist). Interestingly, RTN injection of propranolol (β-AR antagonist) had no effect on respiratory inhibition elicited by applications of NE into the RTN; however, the combined blockade of α2- and β-ARs (coapplication of propranolol and yohimbine) revealed an α1-AR-dependent excitatory response to NE that resulted in increase in DiaEMG frequency and facilitation of active expiration. However, blockade of α1-, α2-, or β-ARs in the RTN had minimal effect on baseline respiratory activity, on central or peripheral chemoreflexes. These results suggest that NE signaling can modulate RTN chemoreceptor function; however, endogenous NE signaling does not contribute to baseline breathing or the ventilatory response to central or peripheral chemoreceptor activity in urethane-anesthetized rats. Copyright © 2016 the American Physiological Society.

WHY IS THE GREAT SOLAR ACTIVE REGION 12192 FLARE-RICH BUT CME-POOR?

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

Sun, Xudong; Bobra, Monica G.; Hoeksema, J. Todd

Solar active region (AR) 12192 of 2014 October hosts the largest sunspot group in 24 years. It is the most prolific flaring site of Cycle 24 so far, but surprisingly produced no coronal mass ejection (CME) from the core region during its disk passage. Here, we study the magnetic conditions that prevented eruption and the consequences that ensued. We find AR 12192 to be “big but mild”; its core region exhibits weaker non-potentiality, stronger overlying field, and smaller flare-related field changes compared to two other major flare-CME-productive ARs (11429 and 11158). These differences are present in the intensive-type indices (e.g.,more » means) but generally not the extensive ones (e.g., totals). AR 12192's large amount of magnetic free energy does not translate into CME productivity. The unexpected behavior suggests that AR eruptiveness is limited by some relative measure of magnetic non-potentiality over the restriction of background field, and that confined flares may leave weaker photospheric and coronal imprints compared to their eruptive counterparts.« less

THE NONPOTENTIALITY OF CORONAE OF SOLAR ACTIVE REGIONS, THE DYNAMICS OF THE SURFACE MAGNETIC FIELD, AND THE POTENTIAL FOR LARGE FLARES

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

Schrijver, Carolus J., E-mail: schrijver@lmsal.com

Flares and eruptions from solar active regions (ARs) are associated with atmospheric electrical currents accompanying distortions of the coronal field away from a lowest-energy potential state. In order to better understand the origin of these currents and their role in M- and X-class flares, I review all AR observations made with Solar Dynamics Observatory (SDO)/Helioseismic and Magnetic Imager and SDO/Atmospheric Imaging Assembly from 2010 May through 2014 October within ≈40° from the disk center. I select the roughly 4% of all regions that display a distinctly nonpotential coronal configuration in loops with a length comparable to the scale of themore » AR, and all that emit GOES X-class flares. The data for 41 regions confirm, with a single exception, that strong-field, high-gradient polarity inversion lines (SHILs) created during emergence of magnetic flux into, and related displacement within, pre-existing ARs are associated with X-class flares. Obvious nonpotentiality in the AR-scale loops occurs in six of ten selected regions with X-class flares, all with relatively long SHILs along their primary polarity inversion line, or with a long internal filament there. Nonpotentiality can exist in ARs well past the flux-emergence phase, often with reduced or absent flaring. I conclude that the dynamics of the flux involved in the compact SHILs is of pre-eminent importance for the large-flare potential of ARs within the next day, but that their associated currents may not reveal themselves in AR-scale nonpotentiality. In contrast, AR-scale nonpotentiality, which can persist for many days, may inform us about the eruption potential other than those from SHILs which is almost never associated with X-class flaring.« less

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.

VizieR Online Data Catalog: Complex network for solar active regions (Daei+, 2017)

NASA Astrophysics Data System (ADS)

Daei, F.; Safari, H.; Dadashi, N.

2018-03-01

The solar monitor (www.solarmonitor.org) records the solar data observed by several solar space observatories and missions (e.g., GOES, GONG, ACE, STEREO, SDO, etc.). 4227 solar active regions (ARs) during 1999 January 1 to 2017 April 14 used for building the AR network are listed in table 1. See section 2 for further details. (1 data file).

STATISTICAL PROPERTIES OF SOLAR ACTIVE REGIONS OBTAINED FROM AN AUTOMATIC DETECTION SYSTEM AND THE COMPUTATIONAL BIASES

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

Zhang Jie; Wang Yuming; Liu Yang, E-mail: jzhang7@gmu.ed

We have developed a computational software system to automate the process of identifying solar active regions (ARs) and quantifying their physical properties based on high-resolution synoptic magnetograms constructed from Michelson Doppler Imager (MDI; on board the SOHO spacecraft) images from 1996 to 2008. The system, based on morphological analysis and intensity thresholding, has four functional modules: (1) intensity segmentation to obtain kernel pixels, (2) a morphological opening operation to erase small kernels, which effectively remove ephemeral regions and magnetic fragments in decayed ARs, (3) region growing to extend kernels to full AR size, and (4) the morphological closing operation tomore » merge/group regions with a small spatial gap. We calculate the basic physical parameters of the 1730 ARs identified by the auto system. The mean and maximum magnetic flux of individual ARs are 1.67 x 10{sup 22} Mx and 1.97 x 10{sup 23} Mx, while that per Carrington rotation are 1.83 x 10{sup 23} Mx and 6.96 x 10{sup 23} Mx, respectively. The frequency distributions of ARs with respect to both area size and magnetic flux follow a log-normal function. However, when we decrease the detection thresholds and thus increase the number of detected ARs, the frequency distribution largely follows a power-law function. We also find that the equatorward drifting motion of the AR bands with solar cycle can be described by a linear function superposed with intermittent reverse driftings. The average drifting speed over one solar cycle is 1{sup o}.83{+-}0{sup o}.04 yr{sup -1} or 0.708 {+-} 0.015 m s{sup -1}.« less

Speed of CMEs and the Magnetic Non-Potentiality of their Source Active Regions

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv Kumar; Falconer, David Allen; Moore, Ronald L.; Venkatakrishnan, P.; Winebarger, Amy R.; Khazanov, Igor G.

2014-01-01

Most fast coronal mass ejections (CMEs) originate from solar active regions (ARs). Non-potentiality of ARs plausibly determines the speed of CMEs in the outer corona. Several other unexplored parameters might be important as well. To find out the relation between the intial speed of CMEs and the non-potentiality of source ARs, we identified over a hundred of CMEs with source ARs via their co-produced flares. The speed of the CMEs are collected from the SOHO LASCO CME catalog. We have used vector magnetograms obtained with HMI/SDO, to evaluate various magnetic non-potentiality parameters, e.g. magnetic free-energy proxies, twist, shear angle, signed shear angle, net current etc. We have also included several other parameters e.g. total unsigned flux, magnetic area of ARs, area of sunspots, to investigate their correlation, if any, with the initial speeds of CMEs. Our preliminary results show that the ARs with larger non-potentiality and area produce faster CMEs but they can also produce slow ones. The ARs with lesser non-potentiality and area generally produce only slower CMEs.

THE MAGNETIC CLASSIFICATION OF SOLAR ACTIVE REGIONS 1992–2015

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

Jaeggli, S. A.; Norton, A. A., E-mail: sarah.jaeggli@nasa.gov

The purpose of this Letter is to address a blindspot in our knowledge of solar active region (AR) statistics. To the best of our knowledge, there are no published results showing the variation of the Mount Wilson magnetic classifications as a function of solar cycle based on modern observations. We show statistics for all ARs reported in the daily Solar Region Summary from 1992 January 1 to 2015 December 31. We find that the α and β class ARs (including all sub-groups, e.g., βγ, βδ) make up fractions of approximately 20% and 80% of the sample, respectively. This fraction ismore » relatively constant during high levels of activity; however, an increase in the α fraction to about 35% and and a decrease in the β fraction to about 65% can be seen near each solar minimum and are statistically significant at the 2σ level. Over 30% of all ARs observed during the years of solar maxima were appended with the classifications γ and/or δ, while these classifications account for only a fraction of a percent during the years near the solar minima. This variation in the AR types indicates that the formation of complex ARs may be due to the pileup of frequent emergence of magnetic flux during solar maximum, rather than the emergence of complex, monolithic flux structures.« less

SUB-SURFACE MERIDIONAL FLOW, VORTICITY, AND THE LIFETIME OF SOLAR ACTIVE REGIONS

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

Maurya, R. A.; Ambastha, A., E-mail: ramajor@prl.res.i, E-mail: ambastha@prl.res.i

Solar sub-surface fluid topology provides an indirect approach to examine the internal characteristics of active regions (ARs). Earlier studies have revealed the prevalence of strong flows in the interior of ARs having complex magnetic fields. Using the Doppler data obtained by the Global Oscillation Network Group project for a sample of 74 ARs, we have discovered the presence of steep gradients in meridional velocity at depths ranging from 1.5 to 5 Mm in flare productive ARs. The sample of these ARs is taken from the Carrington rotations 1980-2052 covering the period 2001 August-2007 January. The gradients showed an interesting hemisphericmore » trend of negative (positive) signs in the northern (southern) hemisphere, i.e., directed toward the equator. We have discovered three sheared layers in the depth range of 0-10 Mm, providing evidence of complex flow structures in several ARs. An important inference derived from our analysis is that the location of the deepest zero vertical vorticity is correlated with the remaining lifetime of ARs. This new finding may be employed as a tool for predicting the life expectancy of an AR.« less

Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity.

PubMed

Chen, Chieh V; Brummet, Jennifer L; Jordan, Cynthia L; Breedlove, S Marc

2016-02-01

We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects.

Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity

PubMed Central

Brummet, Jennifer L.; Jordan, Cynthia L.; Breedlove, S. Marc

2016-01-01

We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90–100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects. PMID:26562258

Active Region Photospheric Magnetic Properties Derived from Line-of-Sight and Radial Fields

NASA Astrophysics Data System (ADS)

Guerra, J. A.; Park, S.-H.; Gallagher, P. T.; Kontogiannis, I.; Georgoulis, M. K.; Bloomfield, D. S.

2018-01-01

The effect of using two representations of the normal-to-surface magnetic field to calculate photospheric measures that are related to the active region (AR) potential for flaring is presented. Several AR properties were computed using line-of-sight (B_{los}) and spherical-radial (Br) magnetograms from the Space-weather HMI Active Region Patch (SHARP) products of the Solar Dynamics Observatory, characterizing the presence and features of magnetic polarity inversion lines, fractality, and magnetic connectivity of the AR photospheric field. The data analyzed correspond to {≈ }4{,}000 AR observations, achieved by randomly selecting 25% of days between September 2012 and May 2016 for analysis at 6-hr cadence. Results from this statistical study include: i) the Br component results in a slight upwards shift of property values in a manner consistent with a field-strength underestimation by the B_{los} component; ii) using the Br component results in significantly lower inter-property correlation in one-third of the cases, implying more independent information as regards the state of the AR photospheric magnetic field; iii) flaring rates for each property vary between the field components in a manner consistent with the differences in property-value ranges resulting from the components; iv) flaring rates generally increase for higher values of properties, except the Fourier spectral power index that has flare rates peaking around a value of 5/3. These findings indicate that there may be advantages in using Br rather than B_{los} in calculating flare-related AR magnetic properties, especially for regions located far from central meridian.

Study of the Effect of Active Regions on the Scattering Polarization in the Solar Corona

NASA Astrophysics Data System (ADS)

Derouich, M.; Badruddin

2018-03-01

The solar photospheric/chromospheric light exciting atoms/ions is not homogeneous because of the presence of active regions (ARs). The effect of ARs on the scattering polarization at the coronal level is an important ingredient for a realistic determination of the magnetic field. This effect is usually disregarded or mixed with other effects in the sense that the degree of its importance is not well known. The aim of this paper is to study the effect of atmospheric inhomogeneities on the coronal scattering polarization. We determined quantitatively the importance of the atmospheric inhomogeneities by using given geometries of solar ARs (plages and sunspots).

FIP bias in a sigmoidal active region

NASA Astrophysics Data System (ADS)

Baker, D.; Brooks, D. H.; Démoulin, P.; van Driel-Gesztelyi, Lidia; Green, L. M.; Steed, K.; Carlyle, J.

2014-01-01

We investigate first ionization potential (FIP) bias levels in an anemone active region (AR) - coronal hole (CH) complex using an abundance map derived from Hinode/EIS spectra. The detailed, spatially resolved abundance map has a large field of view covering 359'' × 485''. Plasma with high FIP bias, or coronal abundances, is concentrated at the footpoints of the AR loops whereas the surrounding CH has a low FIP bias, ~1, i.e. photospheric abundances. A channel of low FIP bias is located along the AR's main polarity inversion line containing a filament where ongoing flux cancellation is observed, indicating a bald patch magnetic topology characteristic of a sigmoid/flux rope configuration.

Relationships Between Photospheric Flows and Solar Flares

NASA Astrophysics Data System (ADS)

Welsch, B. T.; Li, Y.

2013-12-01

Fourier Local Correlation Tracking (FLCT) has been applied to the entire database of 96-minute cadence line-of-sight (LOS) magnetograms from the SOHO/MDI mission, to derive photospheric transverse velocities (u_x,u_y). In a previous study, we applied FLCT to a few dozen active regions (ARs), and found that the "proxy Poynting flux" (PPF) --- the product u B^2, where u is the FLCT flow speed and B is the LOS field divided by the cosine of viewing angle, integrated over each AR --- was statistically related to flare activity. We will present preliminary results of our investigation of the relationship between PPF and flare activity from NOAA's GOES catalog for several hundred ARs identified in NOAA's daily Solar Region Summaries.

Mitochondrial metabolic regulation by GRP78

PubMed Central

Prasad, Manoj; Pawlak, Kevin J.; Burak, William E.; Perry, Elizabeth E.; Marshall, Brendan; Whittal, Randy M.; Bose, Himangshu S.

2017-01-01

Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane. StAR expression and activity are drastically reduced following GRP78 knockdown. StAR folding starts at the MAM region; thus, its cholesterol fostering capacity is regulated by GRP78 long before StAR reaches the mitochondria. In summary, GRP78 is an acute regulator of steroidogenesis at the MAM, regulating the intermediate folding of StAR that is crucial for its activity. PMID:28275724

KDM1A triggers androgen-induced miRNA transcription via H3K4me2 demethylation and DNA oxidation.

PubMed

Yang, Shu; Zhang, Jiyuan; Zhang, Yalong; Wan, Xuechao; Zhang, Congzhe; Huang, Xiaohui; Huang, Wenhua; Pu, Honglei; Pei, Chaohan; Wu, Hai; Huang, Yan; Huang, Shengdong; Li, Yao

2015-06-15

Androgen receptor (AR) is a ligand dependent transcription factor that regulates the transcription of target genes. AR activity is closely involved in the maintenance and progression of prostate cancer. After the binding with androgen, AR moves into nucleus and binds to DNA sequence containing androgen response elements (ARE). Flavin-dependent monoamine oxidase KDM1A is necessary for AR driven transcription while the mechanism remains unclear. The association between androgen-dependent transcription and oxidation was tested through pharmaceutical inhibitions and siRNA knockdown of DNA oxidation repair components in prostate cancer cells. The recruitment of involved proteins and the histone methylation dynamics on ARE region was explored by chromatin immunoprecipitation (ChIP). Oxidation inhibition reduced AR dependent expression of KLK3, TMPRSS2, hsa-miR-125b2, and hsa-miR-133b. And such reduction could be restored by H2 O2 treatment. KDM1A recruitment and H3K4me2 demethylation on ARE regions, which produce H2 O2 , are associated with AR targets transcription. AR targets transcription and coupled oxidation recruit 8-oxoguanine-DNA glycosylase (OGG1) and the nuclease APEX1 to ARE regions. Such recruitment depends on KDM1A, and is necessary for AR targets transcription. Our work underlined the importance of histone demethylation and DNA oxidation/repairing machinery in androgen-dependent transcription. The present finds have implications for research into new druggable targets for prostate cancer relying on the cascade of AR activity regulation. © 2015 Wiley Periodicals, Inc.

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.

Internal Associations of the Acidic Region of Upstream Binding Factor Control Its Nucleolar Localization.

PubMed

Ueshima, Shuhei; Nagata, Kyosuke; Okuwaki, Mitsuru

2017-11-15

Upstream binding factor (UBF) is a member of the high-mobility group (HMG) box protein family, characterized by multiple HMG boxes and a C-terminal acidic region (AR). UBF is an essential transcription factor for rRNA genes and mediates the formation of transcriptionally active chromatin in the nucleolus. However, it remains unknown how UBF is specifically localized to the nucleolus. Here, we examined the molecular mechanisms that localize UBF to the nucleolus. We found that the first HMG box (HMG box 1), the linker region (LR), and the AR cooperatively regulate the nucleolar localization of UBF1. We demonstrated that the AR intramolecularly associates with and attenuates the DNA binding activity of HMG boxes and confers the structured DNA preference to HMG box 1. In contrast, the LR was found to serve as a nuclear localization signal and compete with HMG boxes to bind the AR, permitting nucleolar localization of UBF1. The LR sequence binds DNA and assists the stable chromatin binding of UBF. We also showed that the phosphorylation status of the AR does not clearly affect the localization of UBF1. Our results strongly suggest that associations of the AR with HMG boxes and the LR regulate UBF nucleolar localization. Copyright © 2017 American Society for Microbiology.

Helioseismology of pre-emerging active regions. III. Statistical analysis

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

Barnes, G.; Leka, K. D.; Braun, D. C.

The subsurface properties of active regions (ARs) prior to their appearance at the solar surface may shed light on the process of AR formation. Helioseismic holography has been applied to samples taken from two populations of regions on the Sun (pre-emergence and without emergence), each sample having over 100 members, that were selected to minimize systematic bias, as described in Paper I. Paper II showed that there are statistically significant signatures in the average helioseismic properties that precede the formation of an AR. This paper describes a more detailed analysis of the samples of pre-emergence regions and regions without emergencemore » based on discriminant analysis. The property that is best able to distinguish the populations is found to be the surface magnetic field, even a day before the emergence time. However, after accounting for the correlations between the surface field and the quantities derived from helioseismology, there is still evidence of a helioseismic precursor to AR emergence that is present for at least a day prior to emergence, although the analysis presented cannot definitively determine the subsurface properties prior to emergence due to the small sample sizes.« less

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

PubMed Central

Béïque, Jean-Claude; Imad, Mays; Mladenovic, Ljiljana; Gingrich, Jay A.; Andrade, Rodrigo

2007-01-01

Classic hallucinogens such as lysergic acid diethylamide are thought to elicit their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT2AR). One likely site for these effects is the prefrontal cortex (PFC). Previous studies have shown that activation of 5-HT2ARs in this region results in a robust increase in spontaneous glutamatergic synaptic activity, and these results have led to the widely held idea that hallucinogens elicit their effect by modulating synaptic transmission within the PFC. Here, we combine cellular and molecular biological approaches, including single-cell 5-HT2ARs inactivation and 5-HT2AR rescue over a 5-HT2AR knockout genetic background, to distinguish between competing hypotheses accounting for these effects. The results from these experiments do not support the idea that 5-HT2ARs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that 5-HT2ARs facilitate intrinsic networks within the PFC. Consistent with this idea, we locate a discrete subpopulation of pyramidal cells that is strongly excited by 5-HT2AR activation. PMID:17535909

Numerical Modeling of Flare-productive Active Regions of the Sun

NASA Astrophysics Data System (ADS)

Toriumi, S.; Takasao, S.

2017-12-01

It is known that strong flare events on the Sun take place in active regions (ARs), especially in delta sunspots with closely-packed positive and negative polarities. The delta spots are produced as a result of complex magnetic flux emergence and have strong-field, highly-sheared polarity inversion lines (PILs). Here we report on the numerical simulations of four types of such flare-productive ARs, namely, (1) Spot-Spot, a complex AR with AR-sized PIL, (2) Spot-Satellite, in which a newly-emerging bipole appears next to the pre-existing sunspot, (3) Quadrupole, where two emerging bipoles collide against each other, and (4) Inter-AR, the flares occurring between two separated ARs. We reproduced these four cases by conducting a series of 3D MHD flux emergence simulations and found, for example, that the sheared PILs in these ARs are created through the stretching and advection of horizontal magnetic fields due to relative spot motions. As ARs develop, free magnetic energy becomes stored in the corona, which could be eventually released through flare eruptions. In the presentation, we also mention the relationship between the HMI/SHARP parameters measured in the photosphere and the free energy stored in the corona, and discuss why these parameters successfully predict the flares.

A tale of 10 plutons - Revisited: Age of granitic rocks in the White Mountains, California and Nevada

USGS Publications Warehouse

McKee, E.H.; Conrad, J.E.

1996-01-01

40Ar/39Ar incremental heating analysis and conventional K-Ar age determinations on plutonic rocks of the White Mountains define two stages of magmatic emplacement: Late Cretaceous, between ca. 90 Ma and 75 Ma, and Middle-Late Jurassic, between ca. 180 and 140 Ma. The Jurassic stage can be divided into two substages, 180-165 Ma and 150-140 Ma. Thermal effects of the younger plutons on the older granitoids partially to completely reset ages, making it difficult to determine the age of emplacement and cooling of several of the plutons even by 40Ar/39Ar incremental heating analyses. New data together with published ages and regional geochronological synthesis of the Sierra Nevada batholith indicate that regions within the batholith have coherent periods or episodes of magmatic activity. In the White Mountains and Sierra Nevada directly to the west there was little or no activity in Early Jurassic and Early Cretaceous time; magmatism took place during relatively short intervals of 15 m.y. or less in the Middle and Late Jurassic and Late Cretaceous periods. The new K-Ar and 40Ar/39Ar analyses of granitoids from the White Mountains help, but do not completely clarify the complex history of emplacement, cooling, and reheating of the batholith.

Age and sex differences in oxytocin and vasopressin V1a receptor binding densities in the rat brain: focus on the social decision-making network.

PubMed

Smith, Caroline J W; Poehlmann, Max L; Li, Sara; Ratnaseelan, Aarane M; Bredewold, Remco; Veenema, Alexa H

2017-03-01

Oxytocin (OT) and vasopressin (AVP) regulate various social behaviors via activation of the OT receptor (OTR) and the AVP V1a receptor (V1aR) in the brain. Social behavior often differs across development and between the sexes, yet our understanding of age and sex differences in brain OTR and V1aR binding remains incomplete. Here, we provide an extensive analysis of OTR and V1aR binding density throughout the brain in juvenile and adult male and female rats, with a focus on regions within the social decision-making network. OTR and V1aR binding density were higher in juveniles than in adults in regions associated with reward and socio-spatial memory and higher in adults than in juveniles in key regions of the social decision-making network and in cortical regions. We discuss possible implications of these shifts in OTR and V1aR binding density for the age-specific regulation of social behavior. Furthermore, sex differences in OTR and V1aR binding density were less numerous than age differences. The direction of these sex differences was region-specific for OTR but consistently higher in females than in males for V1aR. Finally, almost all sex differences in OTR and V1aR binding density were already present in juveniles and occurred in regions with denser binding in adults compared to juveniles. Possible implications of these sex differences for the sex-specific regulation of behavior, as well potential underlying mechanisms, are discussed. Overall, these findings provide an important framework for testing age- and sex-specific roles of OTR and V1aR in the regulation of social behavior.

FOXSI-2 Observations and Coronal Heating

NASA Astrophysics Data System (ADS)

Christe, S.; Glesener, L.; Krucker, S.; Ramsey, B.; Ishikawa, S. N.; Buitrago Casas, J. C.; Takahashi, T.; Foster, N.

2015-12-01

Energy release and particle acceleration on the Sun is a frequent occurrence associated with a number of different solar phenomenon including but not limited to solar flares, coronal mass ejections and nanoflares. The exact mechanism through which particles are accelerated and energy is released is still not well understood. This issue is related to the unsolved coronal heating problem, the mystery of the heating mechanism for the million degree solar corona. One prevalent theory posits the existence of a multitude of small flares, dubbed nanoflares. Recent observations of active region AR11890 by IRIS (Testa et al. 2014) are consistent with numerical simulations of heating by impulsive beams of nonthermal electrons, suggesting that nanoflares may be similar to large flares in that they accelerate particles. Furthermore, observations by the EUNIS sounding rocket (Brosius et al. 2014) of faint Fe XIX (592.2 Angstrom) emission in an active region is indicative of plasma at temperatures of at least 8.9 MK providing further evidence of nanoflare heating. One of the best ways to gain insight into accelerated particles on the Sun and the presence of hot plasma is by observing the Sun in hard X-rays (HXR). We present on observations taken during the second successful flight of the Focusing Optics X-ray Solar Imager (FOXSI-2). FOXSI flew on December 11, 2014 with upgraded optics as well as new CdTe strip detectors. FOXSI-2 observed thermal emission (4-15 keV) from at least three active regions (AR#12234, AR#12233, AR#12235) and observed regions of the Sun without active regions. We present on using FOXSI observations to test the presence of hot temperatures in and outside of active regions.

Assessing the climate-scale variability of atmospheric rivers affecting western North America

NASA Astrophysics Data System (ADS)

Gershunov, Alexander; Shulgina, Tamara; Ralph, F. Martin; Lavers, David A.; Rutz, Jonathan J.

2017-08-01

A new method for automatic detection of atmospheric rivers (ARs) is developed and applied to an atmospheric reanalysis, yielding an extensive catalog of ARs land-falling along the west coast of North America during 1948-2017. This catalog provides a large array of variables that can be used to examine AR cases and their climate-scale variability in exceptional detail. The new record of AR activity, as presented, validated and examined here, provides a perspective on the seasonal cycle and the interannual-interdecadal variability of AR activity affecting the hydroclimate of western North America. Importantly, AR intensity does not exactly follow the climatological pattern of AR frequency. Strong links to hydroclimate are demonstrated using a high-resolution precipitation data set. We describe the seasonal progression of AR activity and diagnose linkages with climate variability expressed in Pacific sea surface temperatures, revealing links to Pacific decadal variability, recent regional anomalies, as well as a generally rising trend in land-falling AR activity. The latter trend is consistent with a long-term increase in vapor transport from the warming North Pacific onto the North American continent. The new catalog provides unprecedented opportunities to study the climate-scale behavior and predictability of ARs affecting western North America.

Detailed analysis of dynamic evolution of three Active Regions at the photospheric level before flare and CME occurrence

NASA Astrophysics Data System (ADS)

Ye, Yudong; Korsós, M. B.; Erdélyi, R.

2018-01-01

We present a combined analysis of the applications of the weighted horizontal magnetic gradient (denoted as WGM in Korsós et al. (2015)) method and the magnetic helicity tool (Berger and Field, 1984) employed for three active regions (ARs), namely NOAA AR 11261, AR 11283 and AR 11429. We analysed the time series of photospheric data from the Solar Dynamics Observatory taken between August 2011 and March 2012. During this period the three ARs produced a series of flares (eight M- and six X-class) and coronal mass ejections (CMEs). AR 11261 had four M-class flares and one of them was accompanied by a fast CME. AR 11283 had similar activities with two M- and two X-class flares, but only with a slow CME. Finally, AR 11429 was the most powerful of the three ARs as it hosted five compact and large solar flare and CME eruptions. For applying the WGM method we employed the Debrecen sunspot data catalogue, and, for estimating the magnetic helicity at photospheric level we used the Space-weather HMI Active Region Patches (SHARP's) vector magnetograms from SDO/HMI (Solar Dynamics Observatory/Helioseismic and Magnetic Imager). We followed the evolution of the components of the WGM and the magnetic helicity before the flare and CME occurrences. We found a unique and mutually shared behaviour, called the U-shaped pattern, of the weighted distance component of WGM and of the shearing component of the helicity flux before the flare and CME eruptions. This common pattern is associated with the decreasing-receding phases yet reported only known to be a necessary feature prior to solar flare eruption(s) but found now at the same time in the evolution of the shearing helicity flux. This result leads to the conclusions that (i) the shearing motion of photospheric magnetic field may be a key driver for solar eruption in addition to the flux emerging process, and that (ii) the found decreasing-approaching pattern in the evolution of shearing helicity flux may be another precursor indicator for improving the forecasting of solar eruptions.

WHY IS A FLARE-RICH ACTIVE REGION CME-POOR?

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

Liu, Lijuan; Wang, Yuming; Shen, Chenglong

Solar active regions (ARs) are the major sources of two of the most violent solar eruptions, namely flares and coronal mass ejections (CMEs). The largest AR in the past 24 years, NOAA AR 12192, which crossed the visible disk from 2014 October 17 to 30, unusually produced more than one hundred flares, including 32 M-class and 6 X-class ones, but only one small CME. Flares and CMEs are believed to be two phenomena in the same eruptive process. Why is such a flare-rich AR so CME-poor? We compared this AR with other four ARs; two were productive in both andmore » two were inert. The investigation of the photospheric parameters based on the SDO /HMI vector magnetogram reveals that the flare-rich AR 12192, as with the other two productive ARs, has larger magnetic flux, current, and free magnetic energy than the two inert ARs but, in contrast to the two productive ARs, it has no strong, concentrated current helicity along both sides of the flaring neutral line, indicating the absence of a mature magnetic structure consisting of highly sheared or twisted field lines. Furthermore, the decay index above the AR 12192 is relatively low, showing strong constraint. These results suggest that productive ARs are always large and have enough current and free energy to power flares, but whether or not a flare is accompanied by a CME is seemingly related to (1) the presence of a mature sheared or twisted core field serving as the seed of the CME, or (2) a weak enough constraint of the overlying arcades.« less

Alpha-1A Adrenergic receptor activation increases inhibitory tone in CA1 hippocampus

PubMed Central

Hillman, Kristin L.; Lei, Saobo; Doze, Van A.

2009-01-01

The endogenous catecholamine norepinephrine (NE) exhibits anti-epileptic properties, however it is not well understood which adrenergic receptor (AR) mediates this effect. The aim of this study was to investigate α1-adrenergic receptor (AR) activation in region CA1 of the hippocampus, a subcortical structure often implicated in temporal lobe epilepsies. Using cell-attached and whole-cell recordings in rat hippocampal slices, we confirmed that selective α1-AR activation increases action potential firing in a subpopulation of CA1 interneurons. We found that this response is mediated via the α1A-AR subtype, initiated by sodium influx, and appears independent of second messenger signaling. In CA1 pyramidal cells, α1A-AR activation decreases activity due to increased pre-synaptic GABA and somatostatin release. Examination of post-synaptic receptor involvement revealed that while GABAA receptors mediate the majority of α1A-adrenergic effects on CA1 pyramidal cells, significant contributions are also made by GABAB and somatostatin receptors. Finally, to test whether α1A-AR activation could have potential therapeutic implications, we performed AR agonist challenges using two in vitro epileptiform models. When GABAA receptors were available, α1A-AR activation significantly decreased epileptiform bursting in CA1. Together, our findings directly link stimulation of the α1A-AR subtype to release of GABA and somatostatin at the single cell level and suggest that α1A-AR activation may represent one mechanism by which NE exerts anti-epileptic effects within the hippocampus. PMID:19201164

Xrt And Shinx Joint Flare Study: Ar 11024

NASA Astrophysics Data System (ADS)

Engell, Alexander; Sylwester, J.; Siarkowski, M.

2010-05-01

From 12:00 UT on July 3 through July 7, 2009 SphinX (Solar Photometer IN X-rays) observes 130 flares with active region (AR) 11024 being the only AR on disk. XRT (X-Ray Telescope) is able to observe 64 of these flare events. The combination of both instruments results in a flare study revealing (1) a relationship between flux emergence and flare rate, (2) that the presence of active region loops typically results in different flare morphologies (single and multiple loop flares) then when there is a lack of an active region loop environment where more cusp and point-like flares are observed, (3) cusp and point-like flares often originate from the same location, and (4) a distribution of flare temperatures corresponding to the different flare morphologies. The differences between the observed flare morphologies may occur as the result of the heated plasma through the flaring process being confined by the proximity of loop structures as for the single and multiple loop flares, while for cusp and point-like flares they occur in an early-phase environment that lack loop presence. The continuing flux emergence of AR 11024 likely provides different magnetic interactions and may be the source responsible for all of the flares.

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

A Comparative Study of the Eruptive and Non-eruptive Flares Produced by the Largest Active Region of Solar Cycle 24

NASA Astrophysics Data System (ADS)

Sarkar, Ranadeep; Srivastava, Nandita

2018-02-01

We investigate the morphological and magnetic characteristics of solar active region (AR) NOAA 12192. AR 12192 was the largest region of Solar Cycle 24; it underwent noticeable growth and produced 6 X-class flares, 22 M-class flares, and 53 C-class flares in the course of its disc passage. However, the most peculiar fact of this AR is that it was associated with only one CME in spite of producing several X-class flares. In this work, we carry out a comparative study between the eruptive and non-eruptive flares produced by AR 12192. We find that the magnitude of abrupt and permanent changes in the horizontal magnetic field and Lorentz force are significantly smaller in the case of the confined flares compared to the eruptive one. We present the areal evolution of AR 12192 during its disc passage. We find the flare-related morphological changes to be weaker during the confined flares, whereas the eruptive flare exhibits a rapid and permanent disappearance of penumbral area away from the magnetic neutral line after the flare. Furthermore, from the extrapolated non-linear force-free magnetic field, we examine the overlying coronal magnetic environment over the eruptive and non-eruptive zones of the AR. We find that the critical decay index for the onset of torus instability was achieved at a lower height over the eruptive flaring region, than for the non-eruptive core area. These results suggest that the decay rate of the gradient of overlying magnetic-field strength may play a decisive role to determine the CME productivity of the AR. In addition, the magnitude of changes in the flare-related magnetic characteristics are found to be well correlated with the nature of solar eruptions.

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.

Visualising Androgen Receptor Activity in Male and Female Mice

PubMed Central

Dart, D. Alwyn; Waxman, Jonathan; Aboagye, Eric O.; Bevan, Charlotte L.

2013-01-01

Androgens, required for normal development and fertility of males and females, have vital roles in the reproductive tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a ligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic “ARE-Luc” mouse, expressing a luciferase reporter gene under the control of activated endogenous AR. In vivo imaging of androgen-mediated luciferase activity revealed several strongly expressing tissues in the male mouse as expected and also in certain female tissues. In males the testes, prostate, seminal vesicles and bone marrow all showed high AR activity. In females, strong activity was seen in the ovaries, uterus, omentum tissue and mammary glands. In both sexes AR expression and activity was also found in salivary glands, the eye (and associated glands), adipose tissue, spleen and, notably, regions of the brain. Luciferase protein expression was found in the same cell layers as androgen receptor expression. Additionally, mouse AR expression and activity correlated well with AR expression in human tissues. The anti-androgen bicalutamide reduced luciferase signal in all tissues. Our model demonstrates that androgens can act in these tissues directly via AR, rather than exclusively via androgen aromatisation to estrogens and activation of the estrogen receptor. Additionally, it visually demonstrates the fundamental importance of AR signalling outside the normal role in the reproductive organs. This model represents an important tool for physiological and developmental analysis of androgen signalling, and for characterization of known and novel androgenic or antiandrogenic compounds. PMID:23940781

A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer. | Office of Cancer Genomics

Cancer.gov

Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kb centromeric to the AR. Systematic perturbation of this enhancer using genome editing decreased proliferation by suppressing AR levels. Insertion of an additional copy of this region sufficed to increase proliferation under low androgen conditions and to decrease sensitivity to enzalutamide.

MAGNETIC ENERGY SPECTRA IN SOLAR ACTIVE REGIONS

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

Abramenko, Valentyna; Yurchyshyn, Vasyl

Line-of-sight magnetograms for 217 active regions (ARs) with different flare rates observed at the solar disk center from 1997 January until 2006 December are utilized to study the turbulence regime and its relationship to flare productivity. Data from the SOHO/MDI instrument recorded in the high-resolution mode and data from the BBSO magnetograph were used. The turbulence regime was probed via magnetic energy spectra and magnetic dissipation spectra. We found steeper energy spectra for ARs with higher flare productivity. We also report that both the power index, {alpha}, of the energy spectrum, E(k) {approx} k{sup -}{alpha}, and the total spectral energy,more » W = {integral}E(k)dk, are comparably correlated with the flare index, A, of an AR. The correlations are found to be stronger than those found between the flare index and the total unsigned flux. The flare index for an AR can be estimated based on measurements of {alpha} and W as A = 10{sup b}({alpha}W){sup c}, with b = -7.92 {+-} 0.58 and c = 1.85 {+-} 0.13. We found that the regime of the fully developed turbulence occurs in decaying ARs and in emerging ARs (at the very early stage of emergence). Well-developed ARs display underdeveloped turbulence with strong magnetic dissipation at all scales.« less

Plasma Composition in a Sigmoidal Anemone Active Region

NASA Astrophysics Data System (ADS)

Baker, D.; Brooks, D. H.; Démoulin, P.; van Driel-Gesztelyi, L.; Green, L. M.; Steed, K.; Carlyle, J.

2013-11-01

Using spectra obtained by the EUV Imaging Spectrometer (EIS) instrument onboard Hinode, we present a detailed spatially resolved abundance map of an active region (AR)-coronal hole (CH) complex that covers an area of 359'' × 485''. The abundance map provides first ionization potential (FIP) bias levels in various coronal structures within the large EIS field of view. Overall, FIP bias in the small, relatively young AR is 2-3. This modest FIP bias is a consequence of the age of the AR, its weak heating, and its partial reconnection with the surrounding CH. Plasma with a coronal composition is concentrated at AR loop footpoints, close to where fractionation is believed to take place in the chromosphere. In the AR, we found a moderate positive correlation of FIP bias with nonthermal velocity and magnetic flux density, both of which are also strongest at the AR loop footpoints. Pathways of slightly enhanced FIP bias are traced along some of the loops connecting opposite polarities within the AR. We interpret the traces of enhanced FIP bias along these loops to be the beginning of fractionated plasma mixing in the loops. Low FIP bias in a sigmoidal channel above the AR's main polarity inversion line, where ongoing flux cancellation is taking place, provides new evidence of a bald patch magnetic topology of a sigmoid/flux rope configuration.

THE MAGNETIC SYSTEMS TRIGGERING THE M6.6 CLASS SOLAR FLARE IN NOAA ACTIVE REGION 11158

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

Toriumi, Shin; Iida, Yusuke; Bamba, Yumi

2013-08-20

We report a detailed event analysis of the M6.6 class flare in the active region (AR) NOAA 11158 on 2011 February 13. AR 11158, which consisted of two major emerging bipoles, showed prominent activity including one X- and several M-class flares. In order to investigate the magnetic structures related to the M6.6 event, particularly the formation process of a flare-triggering magnetic region, we analyzed multiple spacecraft observations and numerical results of a flare simulation. We observed that, in the center of this quadrupolar AR, a highly sheared polarity inversion line (PIL) was formed through proper motions of the major magneticmore » elements, which built a sheared coronal arcade lying over the PIL. The observations lend support to the interpretation that the target flare was triggered by a localized magnetic region that had an intrusive structure, namely, a positive polarity penetrating into a negative counterpart. The geometrical relationship between the sheared coronal arcade and the triggering region is consistent with the theoretical flare model based on the previous numerical study. We found that the formation of the trigger region was due to the continuous accumulation of small-scale magnetic patches. A few hours before the flare occurred, the series of emerged/advected patches reconnected with a pre-existing field. Finally, the abrupt flare eruption of the M6.6 event started around 17:30 UT. Our analysis suggests that in the process of triggering flare activity, all magnetic systems on multiple scales are included, not only the entire AR evolution but also the fine magnetic elements.« less

Coronal Jets from Minifilament Eruptions in Active Regions

NASA Technical Reports Server (NTRS)

Martinez, Francisco; Sterling, Alphonse C.; Falconer, David A.; Moore, Ronald L.

2016-01-01

Solar coronal jets are transient (frequently of lifetime approx.10 min) features that shoot out from near the solar surface, become much longer than their width, and occur in all solar regions, including coronal holes, quiet Sun, and active regions (e.g., Shimojo et al. 1996, Cirtain et al. 2007). Sterling et al. (2015) and other studies found that in coronal holes and in quiet Sun the jets result when small-scale filaments, called "minifilaments" erupt onto nearby open or high-reaching field lines. Additional studies found that coronal-jet-onset locations (and hence presumably the minifilament-eruption-onset locations) coincided with locations of magnetic-flux cancelation. For active region (AR) jets however the situation is less clear. Sterling et al. (2016) studied jets in one active region over a 24-hour period; they found that some AR jets indeed resulted from minifilament eruptions, usually originating from locations of episodes of magnetic-flux cancelation. In some cases however they could not determine whether flux was emerging or canceling at the polarity inversion line from which the minifilament erupted, and for other jets of that region minifilaments were not conclusively apparent prior to jet occurrence. Here we further study AR jets, by observing them in a single AR over a one-week period, using X-ray images from Hinode/XRT and EUV/UV images from SDO/AIA, and line-of-sight magnetograms and white-light intensity-grams from SDO/HMI. We initially identified 13 prominent jets in the XRT data, and examined corresponding AIA and HMI data. For at least several of the jets, our findings are consistent with the jets resulting from minifilament eruptions, and originating from sites of magnetic-field cancelation.

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.

Random mutagenesis of two complementarity determining region amino acids yields an unexpectedly high frequency of antibodies with increased affinity for both cognate antigen and autoantigen

PubMed Central

1995-01-01

To gain insight into the mechanism and limitations of antibody affinity maturation leading to memory B cell formation, we generated a phage display library of random mutants at heavy chain variable (V) complementarity determining region 2 positions 58 and 59 of an anti-p- azophenylarsonate (Ars) Fab. Single amino acid substitutions at these positions resulting from somatic hypermutation are recurrent products of affinity maturation in vivo. Most of the ex vivo mutants retained specificity for Ars. Among the many mutants displaying high Ars-binding activity, only one contained a position 58 and 59 amino acid combination that has been previously observed among the monoclonal antibodies (mAbs) derived from Ars-immunized mice. Affinity measurements on 14 of the ex vivo mutants with high Ars-binding activity showed that 11 had higher intrinsic affinities for Ars that the wild-type V region. However, nine of these Fabs also bound strongly to denatured DNA, a property neither displayed by the wild-type V region nor observed among the mutants characteristic of in vivo affinity maturation. These data suggest that ex vivo enhancement of mAb affinity via site-directed and random mutagenesis approaches may often lead to a reduction in antibody specificity that could complicate the use of the resulting mAbs for diagnostic and therapeutic applications. Moreover, the data are compatible with a hypothesis proposing that increased specificity for antigen, rather than affinity per se, is the driving force for formation of the memory B cell compartment. PMID:7650481

The Great Solar Active Region NOAA 12192: Helicity Transport, Filament Formation, and Impact on the Polar Field

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

McMaken, Tyler C.; Petrie, Gordon J. D., E-mail: tmcmaken@gmail.com, E-mail: gpetrie@noao.edu

The solar active region (AR), NOAA 12192, appeared in 2014 October as the largest AR in 24 years. Here we examine the counterintuitive nature of two diffusion-driven processes in the region: the role of helicity buildup in the formation of a major filament, and the relationship between the effects of supergranular diffusion and meridional flow on the AR and on the polar field. Quantitatively, calculations of current helicity and magnetic twist from Helioseismic and Magnetic Imager (HMI) vector magnetograms indicate that, though AR 12192 emerged with negative helicity, positive helicity from subsequent flux emergence, consistent with the hemispheric sign-preference ofmore » helicity, increased over time within large-scale, weak-field regions such as those near the polarity inversion line (PIL). Morphologically, Atmospheric Imaging Assembly observations of filament barbs, sigmoidal patterns, and bases of Fe xii stalks initially exhibited signatures of negative helicity, and the long filament that subsequently formed had a strong positive helicity consistent with the helicity buildup along the PIL. We find from full-disk HMI magnetograms that AR 12192's leading positive flux was initially closer to the equator but, owing either to the region’s magnetic surroundings or to its asymmetric flux density distribution, was transported poleward more quickly on average than its trailing negative flux, contrary to the canonical pattern of bipole flux transport. This behavior caused the AR to have a smaller effect on the polar fields than expected and enabled the formation of the very long neutral line where the filament formed.« less

Coronal Jets from Minifilament Eruptions in Active Regions

NASA Astrophysics Data System (ADS)

Sterling, A. C.; Martinez, F.; Falconer, D. A.; Moore, R. L.

2016-12-01

Solar coronal jets are transient (frequently of lifetime 10 min) features that shoot out from near the solar surface, become much longer than their width, and occur in all solar regions, including coronal holes, quiet Sun, and active regions (e.g., Shimojo et al. 1996, Certain et al. 2007). Sterling et al. (2015) and other studies found that in coronal holes and in quiet Sun the jets result when small-scale filaments, called ``minifilaments,'' erupt onto nearby open or high-reaching field lines. Additional studies found that coronal-jet-onset locations (and hence presumably the minifilament-eruption-onset locations) coincided with locations of magnetic-flux cancellation. For active region (AR) jets however the situation is less clear. Sterling et al. (2016) studied jets in one active region over a 24-hour period; they found that some AR jets indeed resulted from minifilament eruptions, usually originating from locations of episodes of magnetic-flux cancelation. In some cases however they could not determine whether flux was emerging or canceling at the polarity inversion line from which the minifilament erupted; and for other jets of that region minifilaments were not conclusively apparent prior to jet occurrence. Here we further study AR jets, by observing them in a single AR over a one-week period, using X-ray images from Hinode/XRT and EUV/UV images from SDO/AIA, and line-of-sight magnetograms and white-light intensity-grams from SDO/HMI. We initially identified 13 prominent jets in the XRT data, and examined corresponding AIA and HMI data. For at least several of the jets, our findings are consistent with the jets resulting from minifilament eruptions, and originating from sights of magnetic-field cancelation. Thus our findings support that, at least in many cases, AR coronal jets result from the same physical processes that produce coronal jets in quiet-Sun and coronal-hole regions. FM was supportedby the Research Experience for Undergraduates (REU) program at NASA/MSFC and the University of Alabama, Huntsville. Additional support was from the NASA HGI program and the Hinode project.

HMI Data Driven Magnetohydrodynamic Model Predicted Active Region Photospheric Heating Rates: Their Scale Invariant, Flare Like Power Law Distributions, and Their Possible Association With Flares

NASA Technical Reports Server (NTRS)

Goodman, Michael L.; Kwan, Chiman; Ayhan, Bulent; Shang, Eric L.

2017-01-01

A data driven, near photospheric, 3 D, non-force free magnetohydrodynamic model pre- dicts time series of the complete current density, and the resistive heating rate Q at the photosphere in neutral line regions (NLRs) of 14 active regions (ARs). The model is driven by time series of the magnetic field B observed by the Helioseismic & Magnetic Imager on the Solar Dynamics Observatory (SDO) satellite. Spurious Doppler periods due to SDO orbital motion are filtered out of the time series for B in every AR pixel. Errors in B due to these periods can be significant. The number of occurrences N(q) of values of Q > or = q for each AR time series is found to be a scale invariant power law distribution, N(Q) / Q-s, above an AR dependent threshold value of Q, where 0.3952 < or = s < or = 0.5298 with mean and standard deviation of 0.4678 and 0.0454, indicating little variation between ARs. Observations show that the number of occurrences N(E) of coronal flares with a total energy released > or = E obeys the same type of distribution, N(E) / E-S, above an AR dependent threshold value of E, with 0.38 < or approx. S < or approx. 0.60, also with little variation among ARs. Within error margins the ranges of s and S are nearly identical. This strong similarity between N(Q) and N(E) suggests a fundamental connection between the process that drives coronal flares and the process that drives photospheric NLR heating rates in ARs. In addition, results suggest it is plausible that spikes in Q, several orders of magnitude above background values, are correlated with times of the subsequent occurrence of M or X flares.

HMI Data Driven Magnetohydrodynamic Model Predicted Active Region Photospheric Heating Rates: Their Scale Invariant, Flare Like Power Law Distributions, and Their Possible Association With Flares

NASA Technical Reports Server (NTRS)

Goodman, Michael L.; Kwan, Chiman; Ayhan, Bulent; Shang, Eric L.

2017-01-01

A data driven, near photospheric, 3 D, non-force free magnetohydrodynamic model predicts time series of the complete current density, and the resistive heating rate Q at the photosphere in neutral line regions (NLRs) of 14 active regions (ARs). The model is driven by time series of the magnetic field B observed by the Helioseismic and Magnetic Imager on the Solar Dynamics Observatory (SDO) satellite. Spurious Doppler periods due to SDO orbital motion are filtered out of the time series for B in every AR pixel. Errors in B due to these periods can be significant. The number of occurrences N(q) of values of Q > or = q for each AR time series is found to be a scale invariant power law distribution, N(Q) / Q-s, above an AR dependent threshold value of Q, where 0.3952 < or = s < or = 0.5298 with mean and standard deviation of 0.4678 and 0.0454, indicating little variation between ARs. Observations show that the number of occurrences N(E) of coronal flares with a total energy released > or = E obeys the same type of distribution, N(E) / E-S, above an AR dependent threshold value of E, with 0.38 < or approx. S < or approx. 0.60, also with little variation among ARs. Within error margins the ranges of s and S are nearly identical. This strong similarity between N(Q) and N(E) suggests a fundamental connection between the process that drives coronal flares and the process that drives photospheric NLR heating rates in ARs. In addition, results suggest it is plausible that spikes in Q, several orders of magnitude above background values, are correlated with times of the subsequent occurrence of M or X flares.

THE UBIQUITOUS PRESENCE OF LOOPLIKE FINE STRUCTURE INSIDE SOLAR ACTIVE REGIONS

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

Wang, Y.-M., E-mail: yi.wang@nrl.navy.mil

Although most of the solar surface outside active regions (ARs) is pervaded by small-scale fields of mixed polarity, this magnetic “carpet” or “junkyard” is thought to be largely absent inside AR plages and strong network. However, using extreme-ultraviolet images and line-of-sight magnetograms from the Solar Dynamics Observatory, we find that unipolar flux concentrations, both inside and outside ARs, often have small, loop-shaped Fe ix 17.1 and Fe xii 19.3 nm features embedded within them, even though no minority-polarity flux is visible in the corresponding magnetograms. Such looplike structures, characterized by horizontal sizes of ∼3–5 Mm and varying on timescales ofmore » minutes or less, are seen inside bright 17.1 nm moss, as well as in fainter moss-like regions associated with weaker network outside ARs. We also note a tendency for bright coronal loops to show compact, looplike features at their footpoints. Based on these observations, we suggest that present-day magnetograms may be substantially underrepresenting the amount of minority-polarity flux inside plages and strong network, and that reconnection between small bipoles and the overlying large-scale field could be a major source of coronal heating both in ARs and in the quiet Sun.« less

Observed Hydrologic Impacts of Landfalling Atmospheric Rivers in the Salt and Verde River Basins of Arizona, United States

NASA Astrophysics Data System (ADS)

Demaria, Eleonora M. C.; Dominguez, Francina; Hu, Huancui; von Glinski, Gerd; Robles, Marcos; Skindlov, Jonathan; Walter, James

2017-12-01

Atmospheric rivers (ARs), narrow atmospheric water vapor corridors, can contribute substantially to winter precipitation in the semiarid Southwest U.S., where natural ecosystems and humans compete for over-allocated water resources. We investigate the hydrologic impacts of 122 ARs that occurred in the Salt and Verde river basins in northeastern Arizona during the cold seasons from 1979 to 2009. We focus on the relationship between precipitation, snow water equivalent (SWE), soil moisture, and extreme flooding. During the cold season (October through March) ARs contribute an average of 25%/29% of total seasonal precipitation for the Salt/Verde river basins, respectively. However, they contribute disproportionately to total heavy precipitation and account for 64%/72% of extreme total daily precipitation (exceeding the 98th percentile). Excess precipitation during AR occurrences contributes to snow accumulation; on the other hand, warmer than normal temperatures during AR landfallings are linked to rain-on-snow processes, an increase in the basins' area contributing to runoff generation, and higher melting lines. Although not all AR events are linked to extreme flooding in the basins, they do account for larger runoff coefficients. On average, ARs generate 43% of the annual maximum flows for the period studied, with 25% of the events exceeding the 10 year return period. Our analysis shows that the devastating 1993 flooding event in the region was caused by AR events. These results illustrate the importance of AR activity on the hydrology of inland semiarid regions: ARs are critical for water resources, but they can also lead to extreme flooding that affects infrastructure and human activities.

Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus

PubMed Central

Markus, Steven M.; Taneja, Samir S.; Logan, Susan K.; Li, Wenhui; Ha, Susan; Hittelman, Adam B.; Rogatsky, Inez; Garabedian, Michael J.

2002-01-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153–336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153–336 fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation. PMID:11854421

Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.

PubMed

Markus, Steven M; Taneja, Samir S; Logan, Susan K; Li, Wenhui; Ha, Susan; Hittelman, Adam B; Rogatsky, Inez; Garabedian, Michael J

2002-02-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR(153-336), containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR(153-336) fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.

Arf6 negatively controls the rapid recycling of the β2 adrenergic receptor.

PubMed

Macia, Eric; Partisani, Mariagrazia; Paleotti, Olivia; Luton, Frederic; Franco, Michel

2012-09-01

β2-adrenergic receptor (β2AR), a member of the GPCR (G-protein coupled receptor) family, is internalized in a ligand- and β-arrestin-dependent manner into early endosomes, and subsequently recycled back to the plasma membrane. Here, we report that β-arrestin promotes the activation of the small G protein Arf6, which regulates the recycling and degradation of β2AR. We demonstrate in vitro that the C-terminal region of β-arrestin1 interacts directly and simultaneously with Arf6GDP and its specific exchange factor EFA6, to promote Arf6 activation. Similarly, the ligand-mediated activation of β2AR leads to the formation of Arf6GTP in vivo in a β-arrestin-dependent manner. Expression of either EFA6 or an activated Arf6 mutant caused accumulation of β2AR in the degradation pathway. This phenotype could be rescued by the expression of an activated mutant of Rab4, suggesting that Arf6 acts upstream of Rab4. We propose a model in which Arf6 plays an essential role in β2AR desensitization. The ligand-mediated stimulation of β2AR relocates β-arrestin to the plasma membrane, and triggers the activation of Arf6 by EFA6. The activation of Arf6 leads to accumulation of β2AR in the degradation pathway, and negatively controls Rab4-dependent fast recycling to prevent the re-sensitization of β2AR.

Comparison of fMRI data from passive listening and active-response story processing tasks in children

PubMed Central

Vannest, Jennifer J.; Karunanayaka, Prasanna R.; Altaye, Mekibib; Schmithorst, Vincent J.; Plante, Elena M.; Eaton, Kenneth J.; Rasmussen, Jerod M.; Holland, Scott K.

2009-01-01

Purpose To use functional MRI methods to visualize a network of auditory and language-processing brain regions associated with processing an aurally-presented story. We compare a passive listening (PL) story paradigm to an active-response (AR) version including on-line performance monitoring and a sparse acquisition technique. Materials/Methods Twenty children (ages 11−13) completed PL and AR story processing tasks. The PL version presented alternating 30-second blocks of stories and tones; the AR version presented story segments, comprehension questions, and 5s tone sequences, with fMRI acquisitions between stimuli. fMRI data was analyzed using a general linear model approach and paired t-test identifying significant group activation. Results Both tasks activated in primary auditory cortex, superior temporal gyrus bilaterally, left inferior frontal gyrus. The AR task demonstrated more extensive activation, including dorsolateral prefrontal cortex and anterior/posterior cingulate cortex. Comparison of effect size in each paradigm showed a larger effect for the AR paradigm in a left inferior frontal ROI. Conclusion Activation patterns for story processing in children are similar in passive listening and active-response tasks. Increases in extent and magnitude of activation in the AR task are likely associated with memory and attention resources engaged across acquisition intervals. PMID:19306445

Promoter-dependent activity on androgen receptor N-terminal domain mutations in androgen insensitivity syndrome.

PubMed

Tadokoro-Cuccaro, Rieko; Davies, John; Mongan, Nigel P; Bunch, Trevor; Brown, Rosalind S; Audi, Laura; Watt, Kate; McEwan, Iain J; Hughes, Ieuan A

2014-01-01

Androgen receptor (AR) mutations are associated with androgen insensitivity syndrome (AIS). Missense mutations identified in the AR-N-terminal domain (AR-NTD) are rare, and clinical phenotypes are typically mild. We investigated 7 missense mutations and 2 insertion/deletions located in the AR-NTD. This study aimed to elucidate the pathogenic role of AR-NTD mutants in AIS and to use this knowledge to further define AR-NTD function. AR-NTD mutations (Q120E, A159T, G216R, N235K, G248V, L272F, and P380R) were introduced into AR-expression plasmids. Stably expressing cell lines were established for del57L and ins58L. Transactivation was measured using luciferase reporter constructs under the control of GRE and Pem promoters. Intrinsic fluorescence spectroscopy and partial proteolysis studies were performed for mutations which showed reduced activities by using a purified AR-AF1 protein. Pem-luciferase reporter activation was reduced for A159T, N235K, and G248V but not the GRE-luciferase reporter. Protein structure analysis detected no significant change in the AR-AF1 region for these mutations. Reduced cellular expression and transactivation activity were observed for ins58L. The mutations Q120E, G216R, L272F, P380R, and del57L showed small or no detectable changes in function. Thus, clinical and experimental analyses have identified novel AR-signalling defects associated with mutations in the structurally disordered AR-NTD domain in patients with AIS. © 2014 S. Karger AG, Basel.

Magnetic Structure of Sites of Braiding in Hi-C Active Region

NASA Technical Reports Server (NTRS)

Tiwari, S. K.; Alexander, C. E.; Winebarger, A.; Moore, R. L.

2014-01-01

High-resolution Coronal Imager (Hi-C) observations of an active region (AR) corona, at a spatial resolution of 0.2 arcsec, have offered the first direct evidence of field lines braiding, which could deliver sufficient energy to heat the AR corona by current dissipation via magnetic reconnection, a proposal given by Parker three decades ago. The energy required to heat the corona must be transported from the photosphere along the field lines. The mechanism that drives the energy transport to the corona is not yet fully understood. To investigate simultaneous magnetic and intensity structure in and around the AR in detail, we use SDO/HMI+AIA data of + / - 2 hours around the 5 minute Hi-C flight. In the case of the QS, work done by convection/granulation on the inter-granular feet of the coronal field lines probably translates into the heat observed in the corona. In the case of the AR, as here, there could be flux emergence, cancellation/submergence, or shear flows generating large stress and tension in coronal field loops which is released as heat in the corona. However, to the best of our knowledge, there is no observational evidence available to these processes. We investigate the changes taking place in the photospheric feet of the magnetic field involved with brightenings in the Hi-C AR corona. Using HMI 45s magnetograms of four hours we find that, out of the two Hi-C sub-regions where the braiding of field lines were recently detected, flux emergence takes place in one region and flux cancellation in the other. The field in these sub-regions are highly sheared and have apparent high speed plasma flows at their feet. Therefore, shearing flows plausibly power much of the coronal and transition region heating in these areas of the AR. In addition, the presence of large flux emergence/cancellation strongly suggests that the work done by these processes on the pre-existing field also drives much of the observed heating.

The role of serotonin 5-HT2A receptors in memory and cognition

PubMed Central

Zhang, Gongliang; Stackman, Robert W.

2015-01-01

Serotonin 5-HT2A receptors (5-HT2ARs) are widely distributed in the central nervous system, especially in brain region essential for learning and cognition. In addition to endogenous 5-HT, several hallucinogens, antipsychotics, and antidepressants function by targeting 5-HT2ARs. Preclinical studies show that 5-HT2AR antagonists have antipsychotic and antidepressant properties, whereas agonist ligands possess cognition-enhancing and hallucinogenic properties. Abnormal 5-HT2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia, and drug addiction. In addition to its traditional activity as a G protein-coupled receptor (GPCR), recent studies have defined novel operations of 5-HT2ARs. Here we review progress in the (1) receptor anatomy and biology: distribution, signaling, polymerization and allosteric modulation; and (2) receptor functions: learning and memory, hallucination and spatial cognition, and mental disorders. Based on the recent progress in basic research on the 5-HT2AR, it appears that post-training 5-HT2AR activation enhances non-spatial memory consolidation, while pre-training 5-HT2AR activation facilitates fear extinction. Further, the potential influence that 5-HT2AR-elicited visual hallucinations may have on visual cue (i.e., landmark) guided spatial cognition is discussed. We conclude that the development of selective 5-HT2AR modulators to target distinct signaling pathways and neural circuits represents a new possibility for treating emotional, neuropsychiatric, and neurodegenerative disorders. PMID:26500553

NON-NEUTRALIZED ELECTRIC CURRENT PATTERNS IN SOLAR ACTIVE REGIONS: ORIGIN OF THE SHEAR-GENERATING LORENTZ FORCE

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

Georgoulis, Manolis K.; Titov, Viacheslav S.; Mikic, Zoran

Using solar vector magnetograms of the highest available spatial resolution and signal-to-noise ratio, we perform a detailed study of electric current patterns in two solar active regions (ARs): a flaring/eruptive and a flare-quiet one. We aim to determine whether ARs inject non-neutralized (net) electric currents in the solar atmosphere, responding to a debate initiated nearly two decades ago that remains inconclusive. We find that well-formed, intense magnetic polarity inversion lines (PILs) within ARs are the only photospheric magnetic structures that support significant net current. More intense PILs seem to imply stronger non-neutralized current patterns per polarity. This finding revises previousmore » works that claim frequent injections of intense non-neutralized currents by most ARs appearing in the solar disk but also works that altogether rule out injection of non-neutralized currents. In agreement with previous studies, we also find that magnetically isolated ARs remain globally current-balanced. In addition, we confirm and quantify the preference of a given magnetic polarity to follow a given sense of electric currents, indicating a dominant sense of twist in ARs. This coherence effect is more pronounced in more compact ARs with stronger PILs and must be of sub-photospheric origin. Our results yield a natural explanation of the Lorentz force, invariably generating velocity and magnetic shear along strong PILs, thus setting a physical context for the observed pre-eruption evolution in solar ARs.« less

Statistical study of free magnetic energy and flare productivity of solar active regions

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

Su, J. T.; Jing, J.; Wang, S.

Photospheric vector magnetograms from the Helioseismic and Magnetic Imager on board the Solar Dynamic Observatory are utilized as the boundary conditions to extrapolate both nonlinear force-free and potential magnetic fields in solar corona. Based on the extrapolations, we are able to determine the free magnetic energy (FME) stored in active regions (ARs). Over 3000 vector magnetograms in 61 ARs were analyzed. We compare FME with the ARs' flare index (FI) and find that there is a weak correlation (<60%) between FME and FI. FME shows slightly improved flare predictability relative to the total unsigned magnetic flux of ARs in themore » following two aspects: (1) the flare productivity predicted by FME is higher than that predicted by magnetic flux and (2) the correlation between FI and FME is higher than that between FI and magnetic flux. However, this improvement is not significant enough to make a substantial difference in time-accumulated FI, rather than individual flare, predictions.« less

A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer.

PubMed

Takeda, David Y; Spisák, Sándor; Seo, Ji-Heui; Bell, Connor; O'Connor, Edward; Korthauer, Keegan; Ribli, Dezső; Csabai, István; Solymosi, Norbert; Szállási, Zoltán; Stillman, David R; Cejas, Paloma; Qiu, Xintao; Long, Henry W; Tisza, Viktória; Nuzzo, Pier Vitale; Rohanizadegan, Mersedeh; Pomerantz, Mark M; Hahn, William C; Freedman, Matthew L

2018-06-09

Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kb centromeric to the AR. Systematic perturbation of this enhancer using genome editing decreased proliferation by suppressing AR levels. Insertion of an additional copy of this region sufficed to increase proliferation under low androgen conditions and to decrease sensitivity to enzalutamide. Epigenetic data generated in localized prostate tumors and benign specimens support the notion that this region is a developmental enhancer. Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. Copyright © 2018 Elsevier Inc. All rights reserved.

FIP BIAS EVOLUTION IN A DECAYING ACTIVE REGION

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

Baker, D.; Yardley, S. L.; Driel-Gesztelyi, L. van

Solar coronal plasma composition is typically characterized by first ionization potential (FIP) bias. Using spectra obtained by Hinode’s EUV Imaging Spectrometer instrument, we present a series of large-scale, spatially resolved composition maps of active region (AR)11389. The composition maps show how FIP bias evolves within the decaying AR during the period 2012 January 4–6. Globally, FIP bias decreases throughout the AR. We analyzed areas of significant plasma composition changes within the decaying AR and found that small-scale evolution in the photospheric magnetic field is closely linked to the FIP bias evolution observed in the corona. During the AR’s decay phase,more » small bipoles emerging within supergranular cells reconnect with the pre-existing AR field, creating a pathway along which photospheric and coronal plasmas can mix. The mixing timescales are shorter than those of plasma enrichment processes. Eruptive activity also results in shifting the FIP bias closer to photospheric in the affected areas. Finally, the FIP bias still remains dominantly coronal only in a part of the AR’s high-flux density core. We conclude that in the decay phase of an AR’s lifetime, the FIP bias is becoming increasingly modulated by episodes of small-scale flux emergence, i.e., decreasing the AR’s overall FIP bias. Our results show that magnetic field evolution plays an important role in compositional changes during AR development, revealing a more complex relationship than expected from previous well-known Skylab results showing that FIP bias increases almost linearly with age in young ARs.« less

MHD Simulation for Investigating the Dynamic State Transition Responsible for a Solar Eruption in Active Region 12158

NASA Astrophysics Data System (ADS)

Lee, Hwanhee; Magara, Tetsuya

2018-06-01

We present a magnetohydrodynamic model of solar eruption based on the dynamic state transition from the quasi-static state to the eruptive state of an active region (AR) magnetic field. For the quasi-static state before an eruption, we consider the existence of a slow solar wind originating from an AR, which may continuously make the AR magnetic field deviate from mechanical equilibrium. In this model, we perform a three-dimensional magnetohydrodynamic simulation of AR 12158 producing a coronal mass ejection, where the initial magnetic structure of the simulation is given by a nonlinear force-free field derived from an observed photospheric vector magnetic field. We then apply a pressure-driven outflow to the upper part of the magnetic structure to achieve a quasi-static pre-eruptive state. The simulation shows that the eruptive process observed in this AR may be caused by the dynamic state transition of an AR magnetic field, which is essentially different from the destabilization of a static magnetic field. The dynamic state transition is determined from the shape evolution of the magnetic field line according to the κH-mechanism. This work demonstrates how the mechanism works to produce a solar eruption in the dynamic solar corona governed by the gravitational field and the continuous outflows of solar wind.

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells.

PubMed

Han, Yangyang; Huang, Weiwei; Liu, Jiakuan; Liu, Dandan; Cui, Yangyan; Huang, Ruimin; Yan, Jun; Lei, Ming

2017-01-01

Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine ( Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro , and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC.

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

PubMed Central

Han, Yangyang; Huang, Weiwei; Liu, Jiakuan; Liu, Dandan; Cui, Yangyan; Huang, Ruimin; Yan, Jun; Lei, Ming

2017-01-01

Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC. PMID:28638477

Cooling and inferred uplift/erosion history of the Grenville Orogen, Ontario: Constraints from sup 40 Ar/ sup 39 Ar thermochronology

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

Cosca, M.A.

1989-01-01

Thermochronological ({sup 40}Ar/{sup 39}Ar) data are presented from 76 mineral separates of hornblende, muscovite, biotite, phlogopite, and K-feldspar. Samples were selected from regionally metamorphosed gneiss, amphibolite, metasediment, marble, metagabbro and pegmatite across the two major metamorphic belts of the Grenville Province, the Central Metasedimentary Belt (CMB) and the Central Gneiss Belt (CGB). When combined with published temperature estimates for closure to argon diffusion in the phases analyzed, cooling rates from {approximately}500 C to {approximately}120 C of 1-4 C/MA are calculated across the entire Grenville Province of Ontario. Regional uplift/erosion rates for the Grenville Orogen of Ontario have been estimated frommore » the {sup 40}Ar/{sup 39}Ar data, a retrograde P-T path for rocks of the CGB, and an upper time constraint provided by flat, overlying Cambro-Ordovician sediments. Twenty-two of the hornblendes used for thermochronology have been quantitatively analyzed for major elements by microprobe, Fe{sup 2+}/Fe{sup 3+} by wet chemistry, and for H{sub 2}O by manometric measurement. Water activities calculated from hornblende equilibria are typically low (<0.01) because of the exponential dilutions in hornblende (tremolite) activity required by present activity-composition models. An oxyamphibole component of 25% further reduces any amphibole component and the H{sub 2}O activity by as much as 50% below that calculated with simplifying assumption. These findings indicate that different amphibole normalization schemes have a marked effect on the activity calculated for a specific amphibole or H{sub 2}O, and should be carefully evaluated.« less

Numerical Simulations of Flare-productive Active Regions: δ-sunspots, Sheared Polarity Inversion Lines, Energy Storage, and Predictions

NASA Astrophysics Data System (ADS)

Toriumi, Shin; Takasao, Shinsuke

2017-11-01

Solar active regions (ARs) that produce strong flares and coronal mass ejections (CMEs) are known to have a relatively high non-potentiality and are characterized by δ-sunspots and sheared magnetic structures. In this study, we conduct a series of flux emergence simulations from the convection zone to the corona and model four types of active regions that have been observationally suggested to cause strong flares, namely the spot-spot, spot-satellite, quadrupole, and inter-AR cases. As a result, we confirm that δ-spot formation is due to the complex geometry and interaction of emerging magnetic fields, and we find that the strong-field, high-gradient, highly sheared polarity inversion line (PIL) is created by the combined effect of the advection, stretching, and compression of magnetic fields. We show that free magnetic energy builds up in the form of a current sheet above the PIL. It is also revealed that photospheric magnetic parameters that predict flare eruptions reflect the stored free energy with high accuracy, while CME-predicting parameters indicate the magnetic relationship between flaring zones and entire ARs.

Potential Novel Mechanism for Axenfeld-Rieger Syndrome: Deletion of a Distant Region Containing Regulatory Elements of PITX2

PubMed Central

Volkmann, Bethany A.; Zinkevich, Natalya S.; Mustonen, Aki; Schilter, Kala F.; Bosenko, Dmitry V.; Reis, Linda M.; Broeckel, Ulrich; Link, Brian A.

2011-01-01

Purpose. Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Methods. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Results. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. Conclusions. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion. PMID:20881290

MAGNETIC PROPERTIES OF SOLAR ACTIVE REGIONS THAT GOVERN LARGE SOLAR FLARES AND ERUPTIONS

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

Toriumi, Shin; Schrijver, Carolus J.; Harra, Louise K.

Solar flares and coronal mass ejections (CMEs), especially the larger ones, emanate from active regions (ARs). With the aim of understanding the magnetic properties that govern such flares and eruptions, we systematically survey all flare events with Geostationary Orbiting Environmental Satellite levels of ≥M5.0 within 45° from disk center between 2010 May and 2016 April. These criteria lead to a total of 51 flares from 29 ARs, for which we analyze the observational data obtained by the Solar Dynamics Observatory . More than 80% of the 29 ARs are found to exhibit δ -sunspots, and at least three ARs violatemore » Hale’s polarity rule. The flare durations are approximately proportional to the distance between the two flare ribbons, to the total magnetic flux inside the ribbons, and to the ribbon area. From our study, one of the parameters that clearly determine whether a given flare event is CME-eruptive or not is the ribbon area normalized by the sunspot area, which may indicate that the structural relationship between the flaring region and the entire AR controls CME productivity. AR characterization shows that even X-class events do not require δ -sunspots or strong-field, high-gradient polarity inversion lines. An investigation of historical observational data suggests the possibility that the largest solar ARs, with magnetic flux of 2 × 10{sup 23} Mx, might be able to produce “superflares” with energies of the order of 10{sup 34} erg. The proportionality between the flare durations and magnetic energies is consistent with stellar flare observations, suggesting a common physical background for solar and stellar flares.« less

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.

Active Region Soft X-Ray Spectra as Observed Using Sounding Rocket Measurements from the Solar Aspect Monitor (SAM), - a Modified SDO/EVE Instrument

NASA Astrophysics Data System (ADS)

Wieman, S. R.; Didkovsky, L. V.; Woods, T. N.; Jones, A. R.; Caspi, A.; Warren, H. P.

2015-12-01

Observations of solar active regions (ARs) in the soft x-ray spectral range (0.5 to 3.0 nm) were made on sounding rocket flight NASA 36.290 using a modified Solar Aspect Monitor (SAM), a pinhole camera on the EUV Variability Experiment (EVE) sounding rocket instrument. The suite of EVE rocket instruments is designed for under-flight calibrations of the orbital EVE on SDO. While the sounding rocket EVE instrument is for the most part a duplicate of the EVE on SDO, the SAM channel on the rocket version was modified in 2012 to include a free-standing transmission grating so that it could provide spectrally resolved images of the solar disk with the best signal to noise ratio for the brightest features on it, such as ARs. Calibrations of the EVE sounding rocket instrument at the National Institute of Standards and Technology Synchrotron Ultraviolet Radiation Facility (NIST SURF) have provided a measurement of the SAM absolute spectral response function and a mapping of wavelength separation in the grating diffraction pattern. For solar observations, this spectral separation is on a similar scale to the spatial size of the AR on the CCD, so dispersed AR images associated with emission lines of similar wavelength tend to overlap. Furthermore, SAM shares a CCD detector with MEGS-A, a separate EVE spectrometer channel, and artifacts of the MEGS-A signal (a set of bright spectral lines) appear in the SAM images. For these reasons some processing and analysis of the solar images obtained by SAM must be performed in order to determine spectra of the observed ARs. We present a method for determining AR spectra from the SAM rocket images and report initial soft X-ray spectra for two of the major active regions (AR11877 and AR11875) observed on flight 36.290 on 21 October 2013 at about 18:30 UT. We also compare our results with concurrent measurements from other solar soft x-ray instrumentation.

Evidence of Twisted Flux-Tube Emergence in Active Regions

NASA Astrophysics Data System (ADS)

Poisson, M.; Mandrini, C. H.; Démoulin, P.; López Fuentes, M.

2015-03-01

Elongated magnetic polarities are observed during the emergence phase of bipolar active regions (ARs). These extended features, called magnetic tongues, are interpreted as a consequence of the azimuthal component of the magnetic flux in the toroidal flux-tubes that form ARs. We develop a new systematic and user-independent method to identify AR tongues. Our method is based on determining and analyzing the evolution of the AR main polarity inversion line (PIL). The effect of the tongues is quantified by measuring the acute angle [ τ] between the orientation of the PIL and the direction orthogonal to the AR main bipolar axis. We apply a simple model to simulate the emergence of a bipolar AR. This model lets us interpret the effect of magnetic tongues on parameters that characterize ARs ( e.g. the PIL inclination and the tilt angles, and their evolution). In this idealized kinematic emergence model, τ is a monotonically increasing function of the twist and has the same sign as the magnetic helicity. We systematically apply our procedure to a set of bipolar ARs (41 ARs) that were observed emerging in line-of-sight magnetograms over eight years. For most of the cases studied, the tongues only have a small influence on the AR tilt angle since tongues have a much lower magnetic flux than the more concentrated main polarities. From the observed evolution of τ, corrected for the temporal evolution of the tilt angle and its final value when the AR is fully emerged, we estimate the average number of turns in the subphotospherically emerging flux-rope. These values for the 41 observed ARs are below unity, except for one. This indicates that subphotospheric flux-ropes typically have a low amount of twist, i.e. highly twisted flux-tubes are rare. Our results demonstrate that the evolution of the PIL is a robust indicator of the presence of tongues and constrains the amount of twist in emerging flux-tubes.

Bidirectional modulation of hippocampal gamma (20-80 Hz) frequency activity in vitro via alpha(α)- and beta(β)-adrenergic receptors (AR).

PubMed

Haggerty, D C; Glykos, V; Adams, N E; Lebeau, F E N

2013-12-03

Noradrenaline (NA) in the hippocampus plays an important role in memory function and has been shown to modulate different forms of synaptic plasticity. Oscillations in the gamma frequency (20-80 Hz) band in the hippocampus have also been proposed to play an important role in memory functions and, evidence from both in vitro and in vivo studies, has suggested this activity can be modulated by NA. However, the role of different NA receptor subtypes in the modulation of gamma frequency activity has not been fully elucidated. We have found that NA (30 μM) exerts a bidirectional control on the magnitude of kainate-evoked (50-200 nM) gamma frequency oscillations in the cornu Ammonis (CA3) region of the rat hippocampus in vitro via activation of different receptor subtypes. Activation of alpha-adrenergic receptors (α-AR) reduced the power of the gamma frequency oscillation. In contrast, activation of beta-adrenergic receptors (β-AR) caused an increase in the power of the gamma frequency oscillations. Using specific agonists and antagonists of AR receptor subtypes we demonstrated that these effects are mediated specifically via α1A-AR and β1-AR subtypes. NA activated both receptor subtypes, but the α1A-AR-mediated effect predominated, resulting in a reversible suppression of gamma frequency activity. These results suggest that NA is able to differentially modulate on-going gamma frequency oscillatory activity that could result in either increased or decreased information flow through the hippocampus. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

OUTFLOWS AND DARK BANDS AT ARCADE-LIKE ACTIVE REGION CORE BOUNDARIES

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

Scott, J. T.; Martens, P. C. H.; Tarr, L.

Observations from the EUV Imaging Spectrometer (EIS) on board Hinode have revealed outflows and non-thermal line broadening in low intensity regions at the edges of active regions (ARs). We use data from Hinode's EIS, Solar Dynamic Observatory's Atmospheric Imaging Assembly and Helioseismic and Magnetic Imager, and the Transition Region and Coronal Explorer instrument to investigate the boundaries of arcade-like AR cores for NOAA ARs 11112, 10978, and 9077. A narrow, low intensity region that is observed at the core's periphery as a dark band shows outflows and increased spectral line broadening. This dark band is found to exist for daysmore » and appears between the bright coronal loop structures of different coronal topologies. We find a case where the dark band region is formed between the magnetic field from emerging flux and the field of the pre-existing flux. A magnetic field extrapolation indicates that this dark band is coincident with the spine lines or magnetic separatrices in the extrapolated field. This occurs over unipolar regions where the brightened coronal field is separated in connectivity and topology. This separation does not appear to be infinitesimal and an initial estimate of the minimum distance of separation is found to be Almost-Equal-To 1.5-3.5 Mm.« less

Synergistic Activation of Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis by Retinoids: Involvement of cAMP/PKA Signaling

PubMed Central

Manna, Pulak R.; Slominski, Andrzej T.; King, Steven R.; Stetson, Cloyce L.

2014-01-01

Both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the action of retinoids that play important roles in reproductive development and function, as well as steroidogenesis. Regulation of steroid biosynthesis is principally mediated by the steroidogenic acute regulatory protein (StAR); however, the modes of action of retinoids in the regulation of steroidogenesis remain obscure. In this study we demonstrate that all-trans retinoic acid (atRA) enhances StAR expression, but not its phosphorylation (P-StAR), and progesterone production in MA-10 mouse Leydig cells. Activation of the protein kinase A (PKA) cascade, by dibutyrl-cAMP or type I/II PKA analogs, markedly increased retinoid-responsive StAR, P-StAR, and steroid levels. Targeted silencing of endogenous RARα and RXRα, with small interfering RNAs, resulted in decreases in 9-cis RA-stimulated StAR and progesterone levels. Truncation of and mutational alterations in the 5′-flanking region of the StAR gene demonstrated the importance of the −254/−1-bp region in retinoid responsiveness. An oligonucleotide probe encompassing an RXR/liver X receptor recognition motif, located within the −254/−1-bp region, specifically bound MA-10 nuclear proteins and in vitro transcribed/translated RXRα and RARα in EMSAs. Transcription of the StAR gene in response to atRA and dibutyrl-cAMP was influenced by several factors, its up-regulation being dependent on phosphorylation of cAMP response-element binding protein (CREB). Chromatin immunoprecipitation studies revealed the association of phosphorylation of CREB, CREB binding protein, RXRα, and RARα to the StAR promoter. Further studies elucidated that hormone-sensitive lipase plays an important role in atRA-mediated regulation of the steroidogenic response that involves liver X receptor signaling. These findings delineate the molecular events by which retinoids influence cAMP/PKA signaling and provide additional and novel insight into the regulation of StAR expression and steroidogenesis in mouse Leydig cells. PMID:24265455

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots.

PubMed

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants.

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots

PubMed Central

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants. PMID:26230263

The CME Flare Arcade and the Width of the CME in the Outer Corona

NASA Technical Reports Server (NTRS)

Moore, Ron; Falconer, David; Sterling, Alphonse

2008-01-01

Moore, Sterling, & Suess (2007, ApJ, 668, 1221) present evidence that (1) a CME is typically a magnetic bubble, a low-beta gplasmoid with legs h having roughly the 3D shape of a light bulb, and (2) in the outer corona the CME plasmoid is in lateral pressure equilibrium with the ambient magnetic field. They present three CMEs observed by SOHO/LASCO, each from a very different source located near the limb. One of these CMEs came from a compact ejective eruption from a small part of a sunspot active region, another came from a large quiet-region filament eruption, and the third CME, an extremely large and fast one, was produced in tandem with an X20 flare arcade that was centered on a huge delta sunspot. Each of these CMEs had more or less the classic lightbulb silhouette and attained a constant heliocentric angular width in the outer corona. This indicates that the CME plasmoid attained lateral magnetic pressure balance with the ambient radial magnetic field in the outer corona. This lateral pressure balance, together with the standard scenario for CME production by the eruption of a sheared-core magnetic arcade, yields the following simple estimate of the strength B(sub Flare) of the magnetic field in the flare arcade produced together with the CME: B(sub Flare) 1.4(theta CME/theta Flare)sup 2 G, where theta (sub CME) is the heliocentric angular width of the CME plasmoid in the outer corona and theta (sub Flare) is the heliocentric angular width of the full-grown flare arcade. Conversely, theta (sub CME) approximately equal to (R(sub Sun)sup -1(phi(sub Flare)/1.4)sup 1/2 radians, where Flare is the magnetic flux covered by the full-grown flare arcade. In addition to presenting the three CMEs of Moore, Sterling, & Suess (2007) and their agreement with this relation between CME and Flare, we present a further empirical test of this relation. For CMEs that erupt from active regions, the co-produced flare arcade seldom if ever covers the entire active region: if AR is the total magnetic flux of the active region, Flare . AR, and we predict that CME. (R(sub Sun))sup -1(theta AR/1.4)sup 1/2 radians. For a random sample of 31 CMEs that erupted from active regions within 30 of the limb, for each CME we have measured CME from LASCO/C3 and have measured AR from a SOHO/MDI magnetogram of the source active region when it was within 30 of disk center. We find that each CME obeys the above predicted inequality, none having width greater than half of the upper bound given by theta(sub AR). Thus, an active region's magnetic flux content, together with its location on the solar disk, largely determines whether the active region can possibly produce a CME that is wide enough to intercept the Earth.

Elimination of projection effects from vector magnetograms - The pre-flare configuration of active region AR 4474

NASA Technical Reports Server (NTRS)

Venkatakrishnan, P.; Hagyard, M. J.; Hathaway, D. H.

1988-01-01

A simple method of transforming vector magnetograms to heliographic coordinates is demonstrated. The merits of this transformation are illustrated using a vector magnetogram obtained with the MSFC vector magnetograph 80 minutes prior to a white light flare in active region AR 4474 on April 25, 1984. The original magnetogram shows strong magnetic shear along the neutral line at both the flare site and a nonflaring site. The transformation of the magnetogram to heliographic coordinates shows that the elimination of projection effects results in a much shorter length of the sheared region at the nonflaring site than what is inferred from the image plane vector magnetogram. The length of the sheared region at the flare site is relatively less affected by the transformation.

Quality of life and control of allergic rhinitis in patients from regions beyond western Europe and the United States.

PubMed

Maspero, J; Lee, B W; Katelaris, C H; Potter, P C; Cingi, C; Lopatin, A; Saffer, M; Nadeau, G; Walters, R D

2012-12-01

There is comparatively little information on health-related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries, including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Second, in view of the absence of a standardized definition for 'AR control', the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the United States. Furthermore, the findings of the review suggest that 'overall' control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions and cognition. Although some instruments are currently available for measuring control of AR, none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments. © 2012 Blackwell Publishing Ltd.

Optodynamic simulation of β-adrenergic receptor signalling

PubMed Central

Siuda, Edward R.; McCall, Jordan G.; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J.; Anderson, Sonya L.; Planer, William J.; Rogers, John A.; Bruchas, Michael R.

2015-01-01

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo. PMID:26412387

Optodynamic simulation of β-adrenergic receptor signalling.

PubMed

Siuda, Edward R; McCall, Jordan G; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J; Anderson, Sonya L; Planer, William J; Rogers, John A; Bruchas, Michael R

2015-09-28

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo.

CONFINED FLARES IN SOLAR ACTIVE REGION 12192 FROM 2014 OCTOBER 18 TO 29

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

Chen, Huadong; Zhang, Jun; Yang, Shuhong

2015-07-20

Using the observations from the Atmospheric Imaging Assembly and Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory, we investigate 6 X-class and 29 M-class flares occurring in solar active region (AR) 12192 from October 18 to 29. Among them, 30 (including 6 X- and 24 M-class) flares originated from the AR core, and the other 5 M-flares appeared at the AR periphery. Four of the X-flares exhibited similar flaring structures, indicating they were homologous flares with an analogous triggering mechanism. The possible scenario is that photospheric motions of emerged magnetic fluxes lead to shearing of the associatedmore » coronal magnetic field, which then yields a tether-cutting favorable configuration. Among the five periphery M-flares, four were associated with jet activities. The HMI vertical magnetic field data show that the photospheric fluxes of opposite magnetic polarities emerged, converged, and canceled with each other at the footpoints of the jets before the flares. Only one M-flare from the AR periphery was followed by a coronal mass ejection (CME). From October 20 to 26, the mean decay index of the horizontal background field within the height range of 40–105 Mm is below the typical threshold for torus instability onset. This suggests that a strong confinement from the overlying magnetic field might be responsible for the poor CME production of AR 12192.« less

Transcriptional up-regulation of the human androgen receptor by androgen in bone cells.

PubMed

Wiren, K M; Zhang, X; Chang, C; Keenan, E; Orwoll, E S

1997-06-01

Androgen regulation of androgen receptor (AR) expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen. AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Here we characterized the effect of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2 OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the proximal 5'-flanking region of the human AR promoter linked to the chloramphenicol acetyltransferase gene in transfected cultures showed that up-regulation of AR promoter activity by androgen was time and dose dependent. Treatment with other steroid hormones, including progesterone, 17beta-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts. This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue.

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.

Magnetic Properties of Solar Active Regions that Govern Large Solar Flares and Eruptions

NASA Astrophysics Data System (ADS)

Toriumi, Shin; Schrijver, Carolus J.; Harra, Louise; Hudson, Hugh S.; Nagashima, Kaori

2017-08-01

Strong flares and CMEs are often produced from active regions (ARs). In order to better understand the magnetic properties and evolutions of such ARs, we conducted statistical investigations on the SDO/HMI and AIA data of all flare events with GOES levels >M5.0 within 45 deg from the disk center for 6 years from May 2010 (from the beginning to the declining phase of solar cycle 24). Out of the total of 51 flares from 29 ARs, more than 80% have delta-sunspots and about 15% violate Hale’s polarity rule. We obtained several key findings including (1) the flare duration is linearly proportional to the separation of the flare ribbons (i.e., scale of reconnecting magnetic fields) and (2) CME-eruptive events have smaller sunspot areas. Depending on the magnetic properties, flaring ARs can be categorized into several groups, such as spot-spot, in which a highly-sheared polarity inversion line is formed between two large sunspots, and spot-satellite, where a newly-emerging flux next to a mature sunspot triggers a compact flare event. These results point to the possibility that magnetic structures of the ARs determine the characteristics of flares and CMEs. In the presentation, we will also show new results from the systematic flux emergence simulations of delta-sunspot formation and discuss the evolution processes of flaring ARs.

A Recurrent Germline Mutation in the 5'UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation.

PubMed

Hornig, Nadine C; de Beaufort, Carine; Denzer, Friederike; Cools, Martine; Wabitsch, Martin; Ukat, Martin; Kulle, Alexandra E; Schweikert, Hans-Udo; Werner, Ralf; Hiort, Olaf; Audi, Laura; Siebert, Reiner; Ammerpohl, Ole; Holterhus, Paul-Martin

2016-01-01

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5' untranslated region (5'-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5'UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5'UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general.

A Recurrent Germline Mutation in the 5’UTR of the Androgen Receptor Causes Complete Androgen Insensitivity by Activating Aberrant uORF Translation

PubMed Central

Hornig, Nadine C.; de Beaufort, Carine; Denzer, Friederike; Cools, Martine; Wabitsch, Martin; Ukat, Martin; Kulle, Alexandra E.; Schweikert, Hans-Udo; Werner, Ralf; Hiort, Olaf; Audi, Laura; Siebert, Reiner; Ammerpohl, Ole; Holterhus, Paul-Martin

2016-01-01

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5’ untranslated region (5’-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5′UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5′UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general. PMID:27110943

Evolution of the magnetic helicity flux during the formation and eruption of flux ropes

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

Romano, P.; Zuccarello, F. P.; Guglielmino, S. L.

We describe the evolution and the magnetic helicity flux for two active regions (ARs) since their appearance on the solar disk: NOAA 11318 and NOAA 11675. Both ARs hosted the formation and destabilization of magnetic flux ropes. In the former AR, the formation of the flux rope culminated in a flare of C2.3 GOES class and a coronal mass ejection (CME) observed by Large Angle and Spectrometric Coronagraph Experiment. In the latter AR, the region hosting the flux rope was involved in several flares, but only a partial eruption with signatures of a minor plasma outflow was observed. We foundmore » a different behavior in the accumulation of the magnetic helicity flux in the corona, depending on the magnetic configuration and on the location of the flux ropes in the ARs. Our results suggest that the complexity and strength of the photospheric magnetic field is only a partial indicator of the real likelihood of an AR producing the eruption of a flux rope and a subsequent CME.« less

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.

INTERMITTENCY AND MULTIFRACTALITY SPECTRA OF THE MAGNETIC FIELD IN SOLAR ACTIVE REGIONS

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

Abramenko, Valentyna; Yurchyshyn, Vasyl

We present the results of a study of intermittency and multifractality of magnetic structures in solar active regions (ARs). Line-of-sight magnetograms for 214 ARs of different flare productivity observed at the center of the solar disk from 1997 January until 2006 December are utilized. Data from the Michelson Doppler Imager (MDI) instrument on board the Solar and Heliospheric Observatory operating in the high resolution mode, the Big Bear Solar Observatory digital magnetograph, and the Hinode SOT/SP instrument were used. Intermittency spectra were derived from high-order structure functions and flatness functions. The flatness function exponent is a measure of the degreemore » of intermittency. We found that the flatness function exponent at scales below approximately 10 Mm is correlated with flare productivity (the correlation coefficient is -0.63). The Hinode data show that the intermittency regime is extended toward small scales (below 2 Mm) as compared to the MDI data. The spectra of multifractality, derived from the structure functions and flatness functions, are found to be broader for ARs of higher flare productivity as compared to those of low flare productivity. The magnetic structure of high-flaring ARs consists of a voluminous set of monofractals, and this set is much richer than that for low-flaring ARs. The results indicate the relevance of the multifractal organization of the photospheric magnetic fields to the flaring activity. The strong intermittency observed in complex and high-flaring ARs is a hint that we observe a photospheric imprint of enhanced sub-photospheric dynamics.« less

Dressing the Coronal Magnetic Extrapolations of Active Regions with a Parameterized Thermal Structure

NASA Astrophysics Data System (ADS)

Nita, Gelu M.; Viall, Nicholeen M.; Klimchuk, James A.; Loukitcheva, Maria A.; Gary, Dale E.; Kuznetsov, Alexey A.; Fleishman, Gregory D.

2018-01-01

The study of time-dependent solar active region (AR) morphology and its relation to eruptive events requires analysis of imaging data obtained in multiple wavelength domains with differing spatial and time resolution, ideally in combination with 3D physical models. To facilitate this goal, we have undertaken a major enhancement of our IDL-based simulation tool, GX_Simulator, previously developed for modeling microwave and X-ray emission from flaring loops, to allow it to simulate quiescent emission from solar ARs. The framework includes new tools for building the atmospheric model and enhanced routines for calculating emission that include new wavelengths. In this paper, we use our upgraded tool to model and analyze an AR and compare the synthetic emission maps with observations. We conclude that the modeled magneto-thermal structure is a reasonably good approximation of the real one.

Slow Magnetosonic Waves and Fast Flows in Active Region Loops

NASA Technical Reports Server (NTRS)

Ofman, L.; Wang, T. J.; Davila, J. M.

2012-01-01

Recent extreme ultraviolet spectroscopic observations indicate that slow magnetosonic waves are present in active region (AR) loops. Some of the spectral data were also interpreted as evidence of fast (approx 100-300 km/s) quasiperiodic flows. We have performed three-dimensional magnetohydrodynamic (3D MHD) modeling of a bipolar AR that contains impulsively generated waves and flows in coronal loops. The model AR is initiated with a dipole magnetic field and gravitationally stratified density, with an upflow-driven steadily or periodically in localized regions at the footpoints of magnetic loops. The resulting flows along the magnetic field lines of the AR produce higher density loops compared to the surrounding plasma by injection of material into the flux tubes and the establishment of siphon flow.We find that the impulsive onset of flows with subsonic speeds result in the excitation of damped slow magnetosonic waves that propagate along the loops and coupled nonlinearly driven fast-mode waves. The phase speed of the slow magnetosonic waves is close to the coronal sound speed. When the amplitude of the driving pulses is increased we find that slow shock-like wave trains are produced. When the upflows are driven periodically, undamped oscillations are produced with periods determined by the periodicity of the upflows. Based on the results of the 3D MHD model we suggest that the observed slow magnetosonic waves and persistent upflows may be produced by the same impulsive events at the bases of ARs.

Biological and physical controls on O2/Ar, Ar and pCO2 variability at the Western Antarctic Peninsula and in the Drake Passage

NASA Astrophysics Data System (ADS)

Eveleth, R.; Cassar, N.; Doney, S. C.; Munro, D. R.; Sweeney, C.

2017-05-01

Using simultaneous sub-kilometer resolution underway measurements of surface O2/Ar, total O2 and pCO2 from annual austral summer surveys in 2012, 2013 and 2014, we explore the impacts of biological and physical processes on the O2 and pCO2 system spatial and interannual variability at the Western Antarctic Peninsula (WAP). In the WAP, mean O2/Ar supersaturation was (7.6±9.1)% and mean pCO2 supersaturation was (-28±22)%. We see substantial spatial variability in O2 and pCO2 including sub-mesoscale/mesoscale variability with decorrelation length scales of 4.5 km, consistent with the regional Rossby radius. This variability is embedded within onshore-offshore gradients. O2 in the LTER grid region is driven primarily by biological processes as seen by the median ratio of the magnitude of biological oxygen (O2/Ar) to physical oxygen (Ar) supersaturation anomalies (%) relative to atmospheric equilibrium (2.6), however physical processes have a more pronounced influence in the southern onshore region of the grid where we see active sea-ice melting. Total O2 measurements should be interpreted with caution in regions of significant sea-ice formation and melt and glacial meltwater input. pCO2 undersaturation predominantly reflects biological processes in the LTER grid. In contrast we compare these results to the Drake Passage where gas supersaturations vary by smaller magnitudes and decorrelate at length scales of 12 km, in line with latitudinal changes in the regional Rossby radius. Here biological processes induce smaller O2/Ar supersaturations (mean (0.14±1.3)%) and pCO2 undersaturations (mean (-2.8±3.9)%) than in the WAP, and pressure changes, bubble and gas exchange fluxes drive stable Ar supersaturations.

LIGHT BRIDGE IN A DEVELOPING ACTIVE REGION. I. OBSERVATION OF LIGHT BRIDGE AND ITS DYNAMIC ACTIVITY PHENOMENA

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

Toriumi, Shin; Katsukawa, Yukio; Cheung, Mark C. M., E-mail: shin.toriumi@nao.ac.jp

Light bridges, the bright structures that divide the umbra of sunspots and pores into smaller pieces, are known to produce a wide variety of activity events in solar active regions (ARs). It is also known that the light bridges appear in the assembling process of nascent sunspots. The ultimate goal of this series of papers is to reveal the nature of light bridges in developing ARs and the occurrence of activity events associated with the light bridge structures from both observational and numerical approaches. In this first paper, exploiting the observational data obtained by Hinode, the Interface Region Imaging Spectrograph, andmore » the Solar Dynamics Observatory, we investigate the detailed structure of the light bridge in NOAA AR 11974 and its dynamic activity phenomena. As a result, we find that the light bridge has a weak, horizontal magnetic field, which is transported from the interior by a large-scale convective upflow and is surrounded by strong, vertical fields of adjacent pores. In the chromosphere above the bridge, a transient brightening occurs repeatedly and intermittently, followed by a recurrent dark surge ejection into higher altitudes. Our analysis indicates that the brightening is the plasma heating due to magnetic reconnection at lower altitudes, while the dark surge is the cool, dense plasma ejected from the reconnection region. From the observational results, we conclude that the dynamic activity observed in a light bridge structure such as chromospheric brightenings and dark surge ejections are driven by magnetoconvective evolution within the light bridge and its interaction with the surrounding magnetic fields.« less

Temporal and Periodic Variations of Sunspot Counts in Flaring and Non-Flaring Active Regions

NASA Astrophysics Data System (ADS)

Kilcik, A.; Yurchyshyn, V.; Donmez, B.; Obridko, V. N.; Ozguc, A.; Rozelot, J. P.

2018-04-01

We analyzed temporal and periodic variations of sunspot counts (SSCs) in flaring (C-, M-, or X-class flares), and non-flaring active regions (ARs) for nearly three solar cycles (1986 through 2016). Our main findings are as follows: i) temporal variations of monthly means of the daily total SSCs in flaring and non-flaring ARs behave differently during a solar cycle and the behavior varies from one cycle to another; during Solar Cycle 23 temporal SSC profiles of non-flaring ARs are wider than those of flaring ARs, while they are almost the same during Solar Cycle 22 and the current Cycle 24. The SSC profiles show a multi-peak structure and the second peak of flaring ARs dominates the current Cycle 24, while the difference between peaks is less pronounced during Solar Cycles 22 and 23. The first and second SSC peaks of non-flaring ARs have comparable magnitude in the current solar cycle, while the first peak is nearly absent in the case of the flaring ARs of the same cycle. ii) Periodic variations observed in the SSCs profiles of flaring and non-flaring ARs derived from the multi-taper method (MTM) spectrum and wavelet scalograms are quite different as well, and they vary from one solar cycle to another. The largest detected period in flaring ARs is 113± 1.6 days while we detected much longer periodicities (327± 13, 312 ± 11, and 256± 8 days) in the non-flaring AR profiles. No meaningful periodicities were detected in the MTM spectrum of flaring ARs exceeding 55± 0.7 days during Solar Cycles 22 and 24, while a 113± 1.3 days period was detected in flaring ARs of Solar Cycle 23. For the non-flaring ARs the largest detected period was only 31± 0.2 days for Cycle 22 and 72± 1.3 days for the current Cycle 24, while the largest measured period was 327± 13 days during Solar Cycle 23.

PRODUCTIVITY OF SOLAR FLARES AND MAGNETIC HELICITY INJECTION IN ACTIVE REGIONS

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

Park, Sung-hong; Wang Haimin; Chae, Jongchul, E-mail: sp295@njit.ed

The main objective of this study is to better understand how magnetic helicity injection in an active region (AR) is related to the occurrence and intensity of solar flares. We therefore investigate the magnetic helicity injection rate and unsigned magnetic flux, as a reference. In total, 378 ARs are analyzed using SOHO/MDI magnetograms. The 24 hr averaged helicity injection rate and unsigned magnetic flux are compared with the flare index and the flare-productive probability in the next 24 hr following a measurement. In addition, we study the variation of helicity over a span of several days around the times ofmore » the 19 flares above M5.0 which occurred in selected strong flare-productive ARs. The major findings of this study are as follows: (1) for a sub-sample of 91 large ARs with unsigned magnetic fluxes in the range from (3-5) x 10{sup 22} Mx, there is a difference in the magnetic helicity injection rate between flaring ARs and non-flaring ARs by a factor of 2; (2) the GOES C-flare-productive probability as a function of helicity injection displays a sharp boundary between flare-productive ARs and flare-quiet ones; (3) the history of helicity injection before all the 19 major flares displayed a common characteristic: a significant helicity accumulation of (3-45) x 10{sup 42} Mx{sup 2} during a phase of monotonically increasing helicity over 0.5-2 days. Our results support the notion that helicity injection is important in flares, but it is not effective to use it alone for the purpose of flare forecast. It is necessary to find a way to better characterize the time history of helicity injection as well as its spatial distribution inside ARs.« less

Productivity of Solar Flares and Magnetic Helicity Injection in Active Regions

NASA Astrophysics Data System (ADS)

Park, Sung-hong; Chae, Jongchul; Wang, Haimin

2010-07-01

The main objective of this study is to better understand how magnetic helicity injection in an active region (AR) is related to the occurrence and intensity of solar flares. We therefore investigate the magnetic helicity injection rate and unsigned magnetic flux, as a reference. In total, 378 ARs are analyzed using SOHO/MDI magnetograms. The 24 hr averaged helicity injection rate and unsigned magnetic flux are compared with the flare index and the flare-productive probability in the next 24 hr following a measurement. In addition, we study the variation of helicity over a span of several days around the times of the 19 flares above M5.0 which occurred in selected strong flare-productive ARs. The major findings of this study are as follows: (1) for a sub-sample of 91 large ARs with unsigned magnetic fluxes in the range from (3-5) × 1022 Mx, there is a difference in the magnetic helicity injection rate between flaring ARs and non-flaring ARs by a factor of 2; (2) the GOES C-flare-productive probability as a function of helicity injection displays a sharp boundary between flare-productive ARs and flare-quiet ones; (3) the history of helicity injection before all the 19 major flares displayed a common characteristic: a significant helicity accumulation of (3-45) × 1042 Mx2 during a phase of monotonically increasing helicity over 0.5-2 days. Our results support the notion that helicity injection is important in flares, but it is not effective to use it alone for the purpose of flare forecast. It is necessary to find a way to better characterize the time history of helicity injection as well as its spatial distribution inside ARs.

Studying the Transfer of Magnetic Helicity in Solar Active Regions with the Connectivity-based Helicity Flux Density Method

NASA Astrophysics Data System (ADS)

Dalmasse, K.; Pariat, É.; Valori, G.; Jing, J.; Démoulin, P.

2018-01-01

In the solar corona, magnetic helicity slowly and continuously accumulates in response to plasma flows tangential to the photosphere and magnetic flux emergence through it. Analyzing this transfer of magnetic helicity is key for identifying its role in the dynamics of active regions (ARs). The connectivity-based helicity flux density method was recently developed for studying the 2D and 3D transfer of magnetic helicity in ARs. The method takes into account the 3D nature of magnetic helicity by explicitly using knowledge of the magnetic field connectivity, which allows it to faithfully track the photospheric flux of magnetic helicity. Because the magnetic field is not measured in the solar corona, modeled 3D solutions obtained from force-free magnetic field extrapolations must be used to derive the magnetic connectivity. Different extrapolation methods can lead to markedly different 3D magnetic field connectivities, thus questioning the reliability of the connectivity-based approach in observational applications. We address these concerns by applying this method to the isolated and internally complex AR 11158 with different magnetic field extrapolation models. We show that the connectivity-based calculations are robust to different extrapolation methods, in particular with regard to identifying regions of opposite magnetic helicity flux. We conclude that the connectivity-based approach can be reliably used in observational analyses and is a promising tool for studying the transfer of magnetic helicity in ARs and relating it to their flaring activity.

Single amino acid substitutions at 2 of 14 positions in an ultra-conserved region of the androgen receptor yield an androgen-binding domain that is reversibly thermolabile

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

Vasiliou, M.; Lumbroso, R.; Alvarado, C.

1994-09-01

The stereochemistry of the androgen receptor (AR) that is responsible for androgen-specific binding and for its contribution to the transregulatory attributes of an androgen-receptor complex are unknown. Our objective is to define structure-function relations of the human AR by correlating germline missense mutations at its X-linked locus with its resultant misbehavior. Subjects with Arg773Cys have complete androgen insensitivity. We and several other laboratories have reported that their genital skin fibroblasts (GSF) have negligible androgen-binding activity at 37{degrees}. We have found that Phe763Leu also causes CAI, but with approximately 10 fmol/mg protein androgen-binding activity at 37{degrees} (R-deficient). Within COS-1 cells transfectedmore » with each mutant AR cDNA, Phe763Leu and Arg773Cys androgen-binding activities are reversibly thermolabile, by a factor of 2, at 37{degrees} versus 22{degrees}, only in the presence of androgen; in the absence of androgen they are thermostable at 37{degrees}. We have discovered that (for a reason yet unknown) the GSF from a third family with Arg773Cys (and no other coding sequence mutation) have 20-40 mol/mg protein of androgen-binding activity at 37{degrees} when measured with 3-6 nFM androgen. This activity reversibly doubles at 22{degrees}. The reversible thermolability of an AR with Arg773Cys (and probably with Phe763Leu) is demonstrable within GSF. Ligand-dependence of this thermolability implies that ligand induces these mutant AR to undergo a deviant conformational change in, or near, a 14-aa region that shares 90% identity/similarity with its closest receptor relatives.« less

Features of Microwave Radiation and Magnetographic Characteristics of Solar Active Region NOAA 12242 Before the X1.8 Flare on December 20, 2014

NASA Astrophysics Data System (ADS)

Abramov-Maximov, V. E.; Borovik, V. N.; Opeikina, L. V.; Tlatov, A. G.; Yasnov, L. V.

2017-12-01

This paper continues the cycle of authors' works on the detection of precursors of large flares (M5 and higher classes) in active regions (ARs) of the Sun by their microwave radiation and magnetographic characteristics. Generalization of the detected precursors of strong flares can be used to develop methods for their prediction. This paper presents an analysis of the development of NOAA AR 12242, in which an X1.8 flare occurred on December 20, 2014. The analysis is based on regular multiazimuth and multiwavelength observations with the RATAN-600 radio telescope in the range 1.65-10 cm with intensity and circular polarization analysis and data from the Solar Dynamics Observatory (SDO). It was found that a new component appeared in the AR microwave radiation two days before the X-flare. It became dominant in the AR the day before the flare and significantly decreased after the flare. The use of multiazimuth observations from RATAN-600 and observations at 1.76 cm from the Nobeyama Radioheliograph made it possible to identify the radio source that appeared before the X-flare with the site of the closest convergence of opposite polarity fields near the neutral line in the AR. It was established that the X-flare occurred 20 h after the total gradient of the magnetic field of the entire region calculated from SDO/HMI data reached its maximum value. Analysis of the evolution of the microwave source that appeared before the X-flare in AR 12242 and comparison of its parameters with the parameters of other components of the AR microwave radiation showed that the new source can be classified as neutral line associated sources (NLSs), which were repeatedly detected by the RATAN-600 and other radio telescopes 1-3 days before the large flares.

40Ar/39Ar laser fusion and K-Ar ages from Lathrop Wells, Nevada, and Cima, California. The age of the latest volcanic activity in the Yucca Mountain area

USGS Publications Warehouse

Turrin, Brent D.; Champion, Duane E.; ,

1991-01-01

K-Ar and 40Ar/39Ar ages from the Lathrop Wells volcanic center, Nevada, and from the Cima volcanic field, California, indicate that the recently reported 20-ka age estimate for the Lathrop Wells volcanic center is incorrect. Instead an age of 119??11 to 141??10 ka is indicated for the Lathrop Wells volcanic center. This age corrected is concordant with the ages determined by two independent isotopic geochronometric techniques and with the stratigraphy of surficial deposits in the Yucca Mountain region. In addition, paleomagnetic data and radiometric age data indicate only two volcanic events at the Lathrop Wells volcanic center that are probably closely linked in time, not as many as five as recently reported.

A Co-Opted Hormonal Cascade Activates Dormant Adventitious Root Primordia upon Flooding in Solanum dulcamara.

PubMed

Dawood, Thikra; Yang, Xinping; Visser, Eric J W; Te Beek, Tim A H; Kensche, Philip R; Cristescu, Simona M; Lee, Sangseok; Floková, Kristýna; Nguyen, Duy; Mariani, Celestina; Rieu, Ivo

2016-04-01

Soil flooding is a common stress factor affecting plants. To sustain root function in the hypoxic environment, flooding-tolerant plants may form new, aerenchymatous adventitious roots (ARs), originating from preformed, dormant primordia on the stem. We investigated the signaling pathway behind AR primordium reactivation in the dicot species Solanum dulcamara Transcriptome analysis indicated that flooding imposes a state of quiescence on the stem tissue, while increasing cellular activity in the AR primordia. Flooding led to ethylene accumulation in the lower stem region and subsequently to a drop in abscisic acid (ABA) level in both stem and AR primordia tissue. Whereas ABA treatment prevented activation of AR primordia by flooding, inhibition of ABA synthesis was sufficient to activate them in absence of flooding. Together, this reveals that there is a highly tissue-specific response to reduced ABA levels. The central role for ABA in the response differentiates the pathway identified here from the AR emergence pathway known from rice (Oryza sativa). Flooding and ethylene treatment also induced expression of the polar auxin transporter PIN2, and silencing of this gene or chemical inhibition of auxin transport inhibited primordium activation, even though ABA levels were reduced. Auxin treatment, however, was not sufficient for AR emergence, indicating that the auxin pathway acts in parallel with the requirement for ABA reduction. In conclusion, adaptation of S. dulcamara to wet habitats involved co-option of a hormonal signaling cascade well known to regulate shoot growth responses, to direct a root developmental program upon soil flooding. © 2016 American Society of Plant Biologists. All Rights Reserved.

A Co-Opted Hormonal Cascade Activates Dormant Adventitious Root Primordia upon Flooding in Solanum dulcamara1[OPEN

PubMed Central

Dawood, Thikra; Kensche, Philip R.; Cristescu, Simona M.; Mariani, Celestina

2016-01-01

Soil flooding is a common stress factor affecting plants. To sustain root function in the hypoxic environment, flooding-tolerant plants may form new, aerenchymatous adventitious roots (ARs), originating from preformed, dormant primordia on the stem. We investigated the signaling pathway behind AR primordium reactivation in the dicot species Solanum dulcamara. Transcriptome analysis indicated that flooding imposes a state of quiescence on the stem tissue, while increasing cellular activity in the AR primordia. Flooding led to ethylene accumulation in the lower stem region and subsequently to a drop in abscisic acid (ABA) level in both stem and AR primordia tissue. Whereas ABA treatment prevented activation of AR primordia by flooding, inhibition of ABA synthesis was sufficient to activate them in absence of flooding. Together, this reveals that there is a highly tissue-specific response to reduced ABA levels. The central role for ABA in the response differentiates the pathway identified here from the AR emergence pathway known from rice (Oryza sativa). Flooding and ethylene treatment also induced expression of the polar auxin transporter PIN2, and silencing of this gene or chemical inhibition of auxin transport inhibited primordium activation, even though ABA levels were reduced. Auxin treatment, however, was not sufficient for AR emergence, indicating that the auxin pathway acts in parallel with the requirement for ABA reduction. In conclusion, adaptation of S. dulcamara to wet habitats involved co-option of a hormonal signaling cascade well known to regulate shoot growth responses, to direct a root developmental program upon soil flooding. PMID:26850278

Time-space mapping of Easter Chain volcanism

NASA Astrophysics Data System (ADS)

O'Connor, John M.; Stoffers, Peter; McWilliams, Michael O.

1995-12-01

New 40Ar/ 39Ar and published K sbnd Ar ages show that the locus of volcanism along the Easter Volcanic Chain (EVC) has shifted systematically from the Nazca Ridge, at about 26 m.y., to the recently active Sala y Gomez Island/Easter Island region. This indicates a plume rather than a hotline (i.e., mantle roll) origin for the EVC. The time-space distribution of ages, combined with published ages for the Galapagos and Juan Fernandez volcanic chains, is used to reconstruct Nazca plate velocities over the past 26 m.y. A plume now located in the region of Sala y Gomez Island is most compatible with these data. West of the plume, the EVC records neither Nazca nor Pacific plate motions. This section of the EVC may be related to westward channeling of plume material to the Pacific-Nazca spreading boundary region.

An MHD Simulation of Solar Active Region 11158 Driven with a Time-dependent Electric Field Determined from HMI Vector Magnetic Field Measurement Data

NASA Astrophysics Data System (ADS)

Hayashi, Keiji; Feng, Xueshang; Xiong, Ming; Jiang, Chaowei

2018-03-01

For realistic magnetohydrodynamics (MHD) simulation of the solar active region (AR), two types of capabilities are required. The first is the capability to calculate the bottom-boundary electric field vector, with which the observed magnetic field can be reconstructed through the induction equation. The second is a proper boundary treatment to limit the size of the sub-Alfvénic simulation region. We developed (1) a practical inversion method to yield the solar-surface electric field vector from the temporal evolution of the three components of magnetic field data maps, and (2) a characteristic-based free boundary treatment for the top and side sub-Alfvénic boundary surfaces. We simulate the temporal evolution of AR 11158 over 16 hr for testing, using Solar Dynamics Observatory/Helioseismic Magnetic Imager vector magnetic field observation data and our time-dependent three-dimensional MHD simulation with these two features. Despite several assumptions in calculating the electric field and compromises for mitigating computational difficulties at the very low beta regime, several features of the AR were reasonably retrieved, such as twisting field structures, energy accumulation comparable to an X-class flare, and sudden changes at the time of the X-flare. The present MHD model can be a first step toward more realistic modeling of AR in the future.

Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of intrinsic brain activity.

PubMed

Zhang, Jiuquan; Wei, Luqing; Hu, Xiaofei; Xie, Bing; Zhang, Yanling; Wu, Guo-Rong; Wang, Jian

2015-01-01

Parkinson's disease (PD) is a surprisingly heterogeneous neurodegenerative disorder. It is well established that different subtypes of PD present with different clinical courses and prognoses. However, the neural mechanism underlying these disparate presentations is uncertain. Here we used resting-state fMRI (rs-fMRI) and the regional homogeneity (ReHo) method to determine neural activity patterns in the two main clinical subgroups of PD (akinetic-rigid and tremor-dominant). Compared with healthy controls, akinetic-rigid (AR) subjects had increased ReHo mainly in right amygdala, left putamen, bilateral angular gyrus, bilateral medial prefrontal cortex (MPFC), and decreased ReHo in left post cingulate gyrus/precuneus (PCC/PCu) and bilateral thalamus. In contrast, tremor-dominant (TD) patients showed higher ReHo mostly in bilateral angular gyrus, left PCC, cerebellum_crus1, and cerebellum_6, while ReHo was decreased in right putamen, primary sensory cortex (S1), vermis_3, and cerebellum_4_5. These results indicate that AR and TD subgroups both represent altered spontaneous neural activity in default-mode regions and striatum, and AR subjects exhibit more changed neural activity in the mesolimbic cortex (amygdala) but TD in the cerebellar regions. Of note, direct comparison of the two subgroups revealed a distinct ReHo pattern primarily located in the striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) loops. Overall, our findings highlight the involvement of default mode network (DMN) and STC circuit both in AR and TD subtypes, but also underscore the importance of integrating mesolimbic-striatal and CTC loops in understanding neural systems of akinesia and rigidity, as well as resting tremor in PD. This study provides improved understanding of the pathophysiological models of different subtypes of PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

PubMed Central

Zou, Zhiran; Wang, Dan; Lu, Yapeng; Dong, Zhangji; Zhu, Li

2017-01-01

Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis. PMID:28146428

Nuclear scaffold attachment stimulates, but is not essential for ARS activity in Saccharomyces cerevisiae: analysis of the Drosophila ftz SAR.

PubMed Central

Amati, B; Pick, L; Laroche, T; Gasser, S M

1990-01-01

Nuclei isolated from eukaryotic cells can be depleted of histones and most soluble nuclear proteins to isolate a structural framework called the nuclear scaffold. This structure maintains specific interactions with genomic DNA at sites known as scaffold attached regions (SARs), which are thought to be the bases of DNA loops. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, genomic ARS elements are recovered as SARs. In addition, SARs from Drosophila melanogaster bind to yeast nuclear scaffolds in vitro and a subclass of these promotes autonomous replication of plasmids in yeast. In the present report, we present fine mapping studies of the Drosophila ftz SAR, which has both SAR and ARS activities in yeast. The data establish a close relationship between the sequences involved in ARS activity and scaffold binding: ARS elements that can bind the nuclear scaffold in vitro promote more efficient plasmid replication in vivo, but scaffold association is not a strict prerequisite for ARS function. Efficient interaction with nuclear scaffolds from both yeast and Drosophila requires a minimal length of SAR DNA that contains reiteration of a narrow minor groove structure of the double helix. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2123454

SDO/AIA AND HINODE/EIS OBSERVATIONS OF INTERACTION BETWEEN AN EUV WAVE AND ACTIVE REGION LOOPS

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

Yang, Liheng; Zhang, Jun; Li, Ting

2013-09-20

We present detailed analysis of an extreme-ultraviolet (EUV) wave and its interaction with active region (AR) loops observed by the Solar Dynamics Observatory/Atmospheric Imaging Assembly and the Hinode EUV Imaging Spectrometer (EIS). This wave was initiated from AR 11261 on 2011 August 4 and propagated at velocities of 430-910 km s{sup –1}. It was observed to traverse another AR and cross over a filament channel on its path. The EUV wave perturbed neighboring AR loops and excited a disturbance that propagated toward the footpoints of these loops. EIS observations of AR loops revealed that at the time of the wavemore » transit, the original redshift increased by about 3 km s{sup –1}, while the original blueshift decreased slightly. After the wave transit, these changes were reversed. When the EUV wave arrived at the boundary of a polar coronal hole, two reflected waves were successively produced and part of them propagated above the solar limb. The first reflected wave above the solar limb encountered a large-scale loop system on its path, and a secondary wave rapidly emerged 144 Mm ahead of it at a higher speed. These findings can be explained in the framework of a fast-mode magnetosonic wave interpretation for EUV waves, in which observed EUV waves are generated by expanding coronal mass ejections.« less

Magnetic structure of sites of braiding in Hi-C active region

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv Kumar; Alexander, Caroline; Winebarger, Amy R.; Moore, Ronald L.

2014-06-01

High-resolution Coronal Imager (Hi-C) observations of an active region (AR) corona, at a spatial resolution of 0.2 arcsec, have offered the first direct evidence of field lines braiding, which could deliver sufficient energy to heat the AR corona by current dissipation via magnetic reconnection, a proposal given by Parker three decades ago. The energy required to heat the corona must be transported from the photosphere along the field lines. The mechanism that drives the energy transport to the corona is not yet fully understood.To investigate simultaneous magnetic and intensity structure in and around the AR in detail, we use SDO/HMI+AIA data of + / - 2 hours around the 5 minute Hi-C flight. In the case of the QS, work done by convection/granulation on the inter-granular feet of the coronal field lines probably translates into the heat observed in the corona. In the case of the AR, as here, there could be flux emergence, cancellation/submergence, or shear flows generating large stress and tension in coronal field loops which is released as heat in the corona. However, to the best of our knowledge, there is no observational evidence available to these processes. We investigate the changes taking place in the photospheric feet of the magnetic field involved with brightenings in the Hi-C AR corona. Using HMI 45s magnetograms of four hours we find that, out of the two Hi-C sub-regions where the braiding of field lines were recently detected, flux emergence takes place in one region and flux cancellation in the other. The field in these sub-regions are highly sheared and have apparent high speed plasma flows at their feet. Therefore, shearing flows plausibly power much of the coronal and transition region heating in these areas of the AR. In addition, the presence of large flux emergence/cancellation strongly suggests that the work done by these processes on the pre-existing field also drives much of the observed heating.For this work, SKT and CEA were supported by an appointment to the NASA Postdoctoral Program at the NASA Marshall Space Flight Center, administered by Oak Ridge Associated Universities through a contract with NASA, and AW and RLM were supported by funding from the Living With a Star Targeted Research and Technology Program of the Heliophysics Division of NASA's Science Mission Directorate.

Possibilities for Estimating Horizontal Electrical Currents in Active Regions on the Sun

NASA Astrophysics Data System (ADS)

Fursyak, Yu. A.; Abramenko, V. I.

2017-12-01

Part of the "free" magnetic energy associated with electrical current systems in the active region (AR) is released during solar flares. This proposition is widely accepted and it has stimulated interest in detecting electrical currents in active regions. The vertical component of an electric current in the photosphere can be found by observing the transverse magnetic field. At present, however, there are no direct methods for calculating transverse electric currents based on these observations. These calculations require information on the field vector measured simultaneously at several levels in the photosphere, which has not yet been done with solar instrumentation. In this paper we examine an approach to calculating the structure of the square of the density of a transverse electrical current based on a magnetogram of the vertical component of the magnetic field in the AR. Data obtained with the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamic Observatory (SDO) for the AR of NOAA AR 11283 are used. It is shown that (1) the observed variations in the magnetic field of a sunspot and the proposed estimate of the density of an annular horizontal current around the spot are consistent with Faraday's law and (2) the resulting estimates of the magnitude of the square of the density of the horizontal current {j}_{\\perp}^2 = (0.002- 0.004) A2/m4 are consistent with previously obtained values of the density of a vertical current in the photosphere. Thus, the proposed estimate is physically significant and this method can be used to estimate the density and structure of transverse electrical currents in the photosphere.

Photospheric Magnetic Diffusion by Measuring Moments of Active Regions

NASA Astrophysics Data System (ADS)

Engell, Alexander; Longcope, D.

2013-07-01

Photospheric magnetic surface diffusion is an important constraint for the solar dynamo. The HMI Active Region Patches (HARPs) program automatically identify all magnetic regions above a certain flux. In our study we measure the moments of ARs that are no longer actively emerging and can thereby give us good statistical constraints on photospheric diffusion. We also present the diffusion properties as a function of latitude, flux density, and single polarity (leading or following) within each HARP.

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

Behavioral and genetic correlates of the neural response to infant crying among human fathers

PubMed Central

Mascaro, Jennifer S.; Hackett, Patrick D.; Gouzoules, Harold; Lori, Adriana

2014-01-01

Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1–2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering. PMID:24336349

Measurement of Isobaric Analogue Resonances of 47Ar with the Active-Target Time Projection Chamber

NASA Astrophysics Data System (ADS)

Bradt, Joshua William

While the nuclear shell model accurately describes the structure of nuclei near stability, the structure of unstable, neutron-rich nuclei is still an area of active research. One region of interest is the set of nuclei near N=28. The shell model suggests that these nuclei should be approximately spherical due to the shell gap predicted by their magic number of neutrons; however, experiments have shown that the nuclei in this region rapidly become deformed as protons are removed from the spherical 48Ca. This makes 46Ar a particularly interesting system as it lies in a transition region between 48Ca and lighter isotones that are known to be deformed. An experiment was performed at the National Superconducting Cyclotron Laboratory (NSCL) to measure resonant proton scattering on 46Ar. The resonances observed in this reaction correspond to unbound levels in the 47K intermediate state nucleus which are isobaric analogues of states in the 47Ar nucleus. By measuring the spectroscopic factors of these states in 47Ar, we gain information about the single-particle structure of this system, which is directly related to the size of the N=28 shell gap. Four resonances were observed: one corresponding to the ground state in 47Ar, one corresponding its first excited 1/2- state, and two corresponding to 1/2+ states in either 47Ar or the intermediate state nucleus. However, only a limited amount of information about these states could be recovered due to the low experimental statistics and limited angular resolution caused by pileup rejection and the inability to accurately reconstruct the beam particle track. In addition to the nuclear physics motivations, this experiment served as the radioactive beam commissioning for the Active-Target Time Projection Chamber (AT-TPC). The AT-TPC is a new gas-filled charged particle detector built at the NSCL to measure low-energy radioactive beams from the ReA3 facility. Since the gas inside the detector serves as both the tracking medium and the scattering target, reactions are measured over a continuous range of energies with near-4π solid angle coverage. This experiment demonstrated that tracks recorded by the AT-TPC can be reconstructed to a good resolution, and it established the feasibility of performing similar experiments with this detector in the future.

The study of Equatorial coronal hole during maximum phase of Solar Cycle 21, 22, 23 and 24

NASA Astrophysics Data System (ADS)

Karna, Mahendra; Karna, Nishu

2017-08-01

The 11-year Solar Cycle (SC) is characterized by the periodic change in the solar activity like sunspot numbers, coronal holes, active regions, eruptions such as flares and coronal mass ejections. We study the relationship between equatorial coronal holes (ECH) and the active regions (AR) as coronal whole positions and sizes change with the solar cycle. We made a detailed study of equatorial coronal hole for four solar maximum: Solar Cycle 21 (1979,1980,1981 and 1982), Solar Cycle 22 (1989, 1990, 1991 and 1992), Solar Cycle 23 (1999, 2000, 2001 and 2002) and Solar Cycle 24 (2012, 2013, 2014 and 2015). We used publically available NOAA solar coronal hole data for cycle 21 and 22. We measured the ECH region using the EIT and AIA synoptic map for cycle 23 and 24. We noted that in two complete 22-year cycle of solar activity, the equatorial coronal hole numbers in SC 22 is greater than SC 21 and similarly, SC 24 equatorial coronal hole numbers are greater than SC 23. Moreover, we also compared the position of AR and ECH during SC 23 and 24. We used daily Solar Region Summary (SRS) data from SWPC/NOAA website. Our goal is to examine the correlation between equatorial holes, active regions, and flares.

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

Multi-model global assessment of subseasonal prediction skill of atmospheric rivers

NASA Astrophysics Data System (ADS)

Deflorio, M. J.

2017-12-01

Atmospheric rivers (ARs) are global phenomena that are characterized by long, narrow plumes of water vapor transport. They are most often observed in the midlatitudes near climatologically active storm track regions. Because of their frequent association with floods, landslides, and other hydrological impacts on society, there is significant incentive at the intersection of academic research, water management, and policymaking to understand the skill with which state-of-the-art operational weather models can predict ARs weeks-to-months in advance. We use the newly assembled Subseasonal-to-Seasonal (S2S) database, which includes extensive hindcast records of eleven operational weather models, to assess global prediction skill of atmospheric rivers on S2S timescales. We develop a metric to assess AR skill that is suitable for S2S timescales by counting the total number of AR days which occur over each model and observational grid cell during a 2-week time window. This "2-week AR occurrence" metric is suitable for S2S prediction skill assessment because it does not consider discrete hourly or daily AR objects, but rather a smoothed representation of AR occurrence over a longer period of time. Our results indicate that several of the S2S models, especially the ECMWF model, show useful prediction skill in the 2-week forecast window, with significant interannual variation in some regions. We also present results from an experimental forecast of S2S AR prediction skill using the ECMWF and NCEP models.

Successive Homologous Coronal Mass Ejections Driven by Shearing and Converging Motions in Solar Active Region NOAA 12371

NASA Astrophysics Data System (ADS)

Vemareddy, P.

2017-08-01

We study the magnetic field evolution in AR 12371, related to its successive eruptive nature. During the disk transit of seven days, the active region (AR) launched four sequential fast coronal mass ejections (CMEs), which are associated with long duration M-class flares. Morphological study delineates a pre-eruptive coronal sigmoid structure above the polarity inversion line (PIL) similar to Moore et al.’s study. The velocity field derived from tracked magnetograms indicates persistent shear and converging motions of polarity regions about the PIL. While these shear motions continue, the crossed arms of two sigmoid elbows are being brought to interaction by converging motions at the middle of the PIL, initiating the tether-cutting reconnection of field lines and the onset of the CME explosion. The successive CMEs are explained by a cyclic process of magnetic energy storage and release referred to as “sigmoid-to-arcade-to-sigmoid” transformation driven by photospheric flux motions. Furthermore, the continued shear motions inject helicity flux with a dominant negative sign, which contributes to core field twist and its energy by building a twisted flux rope (FR). After a limiting value, the excess coronal helicity is expelled by bodily ejection of the FR, which is initiated by some instability as realized by intermittent CMEs. This AR is in contrast with the confined AR 12192 with a predominant negative sign and larger helicity flux, but much weaker (-0.02 turns) normalized coronal helicity content. While predominant signed helicity flux is a requirement for CME eruption, our study suggests that the magnetic flux normalized helicity flux is a necessary condition accommodating the role of background flux and appeals to a further study of a large sample of ARs.

Successive Homologous Coronal Mass Ejections Driven by Shearing and Converging Motions in Solar Active Region NOAA 12371

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

Vemareddy, P., E-mail: vemareddy@iiap.res.in

We study the magnetic field evolution in AR 12371, related to its successive eruptive nature. During the disk transit of seven days, the active region (AR) launched four sequential fast coronal mass ejections (CMEs), which are associated with long duration M-class flares. Morphological study delineates a pre-eruptive coronal sigmoid structure above the polarity inversion line (PIL) similar to Moore et al.’s study. The velocity field derived from tracked magnetograms indicates persistent shear and converging motions of polarity regions about the PIL. While these shear motions continue, the crossed arms of two sigmoid elbows are being brought to interaction by convergingmore » motions at the middle of the PIL, initiating the tether-cutting reconnection of field lines and the onset of the CME explosion. The successive CMEs are explained by a cyclic process of magnetic energy storage and release referred to as “sigmoid-to-arcade-to-sigmoid” transformation driven by photospheric flux motions. Furthermore, the continued shear motions inject helicity flux with a dominant negative sign, which contributes to core field twist and its energy by building a twisted flux rope (FR). After a limiting value, the excess coronal helicity is expelled by bodily ejection of the FR, which is initiated by some instability as realized by intermittent CMEs. This AR is in contrast with the confined AR 12192 with a predominant negative sign and larger helicity flux, but much weaker (−0.02 turns) normalized coronal helicity content. While predominant signed helicity flux is a requirement for CME eruption, our study suggests that the magnetic flux normalized helicity flux is a necessary condition accommodating the role of background flux and appeals to a further study of a large sample of ARs.« less

PARALLEL EVOLUTION OF QUASI-SEPARATRIX LAYERS AND ACTIVE REGION UPFLOWS

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

Mandrini, C. H.; Cristiani, G. D.; Nuevo, F. A.

2015-08-10

Persistent plasma upflows were observed with Hinode’s EUV Imaging Spectrometer (EIS) at the edges of active region (AR) 10978 as it crossed the solar disk. We analyze the evolution of the photospheric magnetic and velocity fields of the AR, model its coronal magnetic field, and compute the location of magnetic null-points and quasi-sepratrix layers (QSLs) searching for the origin of EIS upflows. Magnetic reconnection at the computed null points cannot explain all of the observed EIS upflow regions. However, EIS upflows and QSLs are found to evolve in parallel, both temporarily and spatially. Sections of two sets of QSLs, calledmore » outer and inner, are found associated to EIS upflow streams having different characteristics. The reconnection process in the outer QSLs is forced by a large-scale photospheric flow pattern, which is present in the AR for several days. We propose a scenario in which upflows are observed, provided that a large enough asymmetry in plasma pressure exists between the pre-reconnection loops and lasts as long as a photospheric forcing is at work. A similar mechanism operates in the inner QSLs; in this case, it is forced by the emergence and evolution of the bipoles between the two main AR polarities. Our findings provide strong support for the results from previous individual case studies investigating the role of magnetic reconnection at QSLs as the origin of the upflowing plasma. Furthermore, we propose that persistent reconnection along QSLs does not only drive the EIS upflows, but is also responsible for the continuous metric radio noise-storm observed in AR 10978 along its disk transit by the Nançay Radio Heliograph.« less

Helium abundance and speed difference between helium ions and protons in the solar wind from coronal holes, active regions, and quiet Sun

NASA Astrophysics Data System (ADS)

Fu, Hui; Madjarska, M. S.; Li, Bo; Xia, LiDong; Huang, ZhengHua

2018-05-01

Two main models have been developed to explain the mechanisms of release, heating and acceleration of the nascent solar wind, the wave-turbulence-driven (WTD) models and reconnection-loop-opening (RLO) models, in which the plasma release processes are fundamentally different. Given that the statistical observational properties of helium ions produced in magnetically diverse solar regions could provide valuable information for the solar wind modelling, we examine the statistical properties of the helium abundance (AHe) and the speed difference between helium ions and protons (vαp) for coronal holes (CHs), active regions (ARs) and the quiet Sun (QS). We find bimodal distributions in the space of AHeand vαp/vA(where vA is the local Alfvén speed) for the solar wind as a whole. The CH wind measurements are concentrated at higher AHeand vαp/vAvalues with a smaller AHedistribution range, while the AR and QS wind is associated with lower AHeand vαp/vA, and a larger AHedistribution range. The magnetic diversity of the source regions and the physical processes related to it are possibly responsible for the different properties of AHeand vαp/vA. The statistical results suggest that the two solar wind generation mechanisms, WTD and RLO, work in parallel in all solar wind source regions. In CH regions WTD plays a major role, whereas the RLO mechanism is more important in AR and QS.

Depressed emission between magnetic arcades near a sunspot

NASA Astrophysics Data System (ADS)

Ryabov, B. I.; Shibasaki, K.

The locations of the depressed emission in microwaves, EUV and soft X-rays are compared with each other and with the location of the plasma outflow in the active region (AR) 8535 on the Sun. We found that two open-field regions overlap the regions of depressed emission near the AR's sunspot. These two open-field regions are simulated with the potential-field source-surface (PFSS) model under radial distances of RSS = 1.8 R⊙ and RSS = 2.5 R⊙. Each open-field region is located between the arcades of the loops of the same magnetic polarity. The former open-field region covers the region of the plasma outflow, which is thus useful for the tests on connection to the heliosphere. The utmost microwave depression of the intensity in the ordinary mode (the Very Large Array 15 GHz observations) also overlaps the region of the plasma outflow and thus indicates this outflow. The lasting for eight days depression in soft X-rays and the SOHO EIT 2.84× 10-8 m images are attributed to the evacuation of as hot coronal plasma as T≥ 2× 106 K from the extended in height (``open") magnetic structures. We conclude that the AR 8535 presents the sunspot atmosphere affected by the large-scale magnetic fields.

SREBF1 Activity is Regulated by an AR/mTOR Nuclear Axis in Prostate Cancer.

PubMed

Audet-Walsh, Etienne; Vernier, Mathieu; Yee, Tracey; Laflamme, Chloe E; Li, Susan; Chen, Yonghong; Giguere, Vincent

2018-05-21

Reprogramming of cellular metabolism is an important feature of prostate cancer (PCa), including altered lipid metabolism. Recently, it was observed that the nuclear fraction of mTOR is essential for the androgen-mediated metabolic reprogramming of PCa cells. Herein, it is demonstrated that the androgen receptor (AR) and mTOR bind to regulatory regions of sterol regulatory element binding transcription factor 1 (SREBF1) to control its expression, while dual activation of these signaling pathways also promotes SREBF1 cleavage and its translocation to the nucleus. Consequently, SREBF1 recruitment to regulatory regions of its target genes is induced upon treatment with the synthetic androgen R1881, an effect abrogated upon inhibition of the mTOR signaling pathway. In turn, pharmacological and genetic inhibition of SREBF1 activity impairs the androgen-mediated induction of the key lipogenic genes fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1). Consistent with these observations, the expression of SREBF1, FASN and SCD1 is significantly correlated in human PCa tumor clinical specimens. Functionally, blockade of SREBF1 activity reduces the androgen-driven lipid accumulation. Interestingly, decreased triglyceride accumulation observed upon SREBF1 inhibition is paralleled by an increase in mitochondrial respiration, indicating a potential rewiring of citrate metabolism in PCa cells. Altogether, these data define an AR/mTOR nuclear axis, in the context of PCa, as a novel pathway regulating SREBF1 activity and citrate metabolism. The finding that an AR/mTOR complex promotes SREBP expression and activity enhances our understanding of the metabolic adaptation necessary for prostate cancer cell growth and suggests novel therapeutic approaches to target metabolic vulnerabilities in tumors. Copyright ©2018, American Association for Cancer Research.

Regulation of the mRNA-binding protein AUF1 by activation of the beta-adrenergic receptor signal transduction pathway.

PubMed

Pende, A; Tremmel, K D; DeMaria, C T; Blaxall, B C; Minobe, W A; Sherman, J A; Bisognano, J D; Bristow, M R; Brewer, G; Port, J

1996-04-05

In both cell culture based model systems and in the failing human heart, beta-adrenergic receptors ( beta-AR) undergo agonist-mediated down-regulation. This decrease correlates closely with down-regulation of its mRNA, an effect regulated in part by changes in mRNA stability. Regulation of mRNA stability has been associated with mRNA-binding proteins that recognize A + U-rich elements within the 3'-untranslated regions of many mRNAs encoding proto-oncogene and cytokine mRNAs. We demonstrate here that the mRNA-binding protein, AUF1, is present in both human heart and in hamster DDT1-MF2 smooth muscle cells and that its abundance is regulated by beta-AR agonist stimulation. In human heart, AUF1 mRNA and protein was significantly increased in individuals with myocardial failure, a condition associated with increases in the beta-adrenergic receptor agonist norepinephrine. In the same hearts, there was a significant decrease (approximately 50%) in the abundance of beta1-AR mRNA and protein. In DDT1-MF2 cells, where agonist-mediated destabilization of beta2-AR mRNA was first described, exposure to beta-AR agonist resulted in a significant increase in AUF1 mRNA and protein (approximately 100%). Conversely, agonist exposure significantly decreased (approximately 40%) beta2-adrenergic receptor mRNA abundance. Last, we demonstrate that AUF1 can be immunoprecipitated from polysome-derived proteins following UV cross-linking to the 3'-untranslated region of the human beta1-AR mRNA and that purified, recombinant p37AUF1 protein also binds to beta1-AR 3'-untranslated region mRNA.

The phytochemical 3,3'-diindolylmethane decreases expression of AR-controlled DNA damage repair genes through repressive chromatin modifications and is associated with DNA damage in prostate cancer cells.

PubMed

Palomera-Sanchez, Zoraya; Watson, Gregory W; Wong, Carmen P; Beaver, Laura M; Williams, David E; Dashwood, Roderick H; Ho, Emily

2017-09-01

Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK). Decreased expression of these genes was accompanied by an increase in repressive chromatin marks, loss of AR occupancy and EZH2 recruitment to their regulatory regions. Decreased DNA repair gene expression was associated with an increase in DNA damage (γH2Ax) and up-regulation of genomic repeat elements LINE1 and α-satellite. Our results suggest that DIM suppresses AR-dependent gene transcription through epigenetic modulation, leading to DNA damage and genome instability in PCa cells. Published by Elsevier Inc.

Magnetic Energy and Helicity in Two Emerging Active Regions in the Sun

NASA Technical Reports Server (NTRS)

Liu, Y.; Schuck, P. W.

2012-01-01

The magnetic energy and relative magnetic helicity in two emerging solar active regions, AR 11072 and AR 11158,are studied. They are computed by integrating over time the energy and relative helicity fluxes across the photosphere. The fluxes consist of two components: one from photospheric tangential flows that shear and braid field lines (shear term), the other from normal flows that advect magnetic flux into the corona (emergence term). For these active regions: (1) relative magnetic helicity in the active-region corona is mainly contributed by the shear term,(2) helicity fluxes from the emergence and the shear terms have the same sign, (3) magnetic energy in the corona (including both potential energy and free energy) is mainly contributed by the emergence term, and(4) energy fluxes from the emergence term and the shear term evolved consistently in phase during the entire flux emergence course.We also examine the apparent tangential velocity derived by tracking field-line footpoints using a simple tracking method. It is found that this velocity is more consistent with tangential plasma velocity than with the flux transport velocity, which agrees with the conclusion by Schuck.

Hi-C Observations of an Active Region Corona, and Investigation of the Underlying Magnetic Structure

NASA Technical Reports Server (NTRS)

Tiwari, S. K.; Alexander, C. E.; Winebarger, A.; Moore, R. L.

2014-01-01

The solar corona is much hotter (>=10(exp 6) K) than its surface (approx 6000 K), puzzling astrophysicists for several decades. Active region (AR) corona is again hotter than the quiet Sun (QS) corona by a factor of 4-10. The most widely accepted mechanism that could heat the active region corona is the energy release by current dissipation via reconnection of braided magnetic field structure, first proposed by E. N. Parker three decades ago. The first observational evidence for this mechanism has only recently been presented by Cirtain et al. by using High-resolution Coronal Imager (Hi-C) observations of an AR corona at a spatial resolution of 0.2 arcsec, which is required to resolve the coronal loops, and was not available before the rocket flight of Hi-C in July 2012. The Hi-C project is led by NASA/MSFC. In the case of the QS, work done by convection/granulation on the inter-granular feet of the coronal field lines translates into the heat observed in the corona. In the case of the AR, as here, there could be flux emergence, cancellation/submergence, or shear flows generating large stress and tension in coronal field loops which is released as heat in the corona. We are currently investigating the changes taking place in photospheric feet of the magnetic field involved with brightenings in the Hi-C AR corona. For this purpose, we are also using SDO/AIA data of +/- 2 hours around the 5 minutes Hi-C flight. In the present talk, I will first summarize some of the results of the Hi-C observations and then present some results from our recent analysis on what photospheric processes feed the magnetic energy that dissipates into heat in coronal loops.

Physics of the Solar Active Regions from Radio Observations

NASA Astrophysics Data System (ADS)

Gelfreikh, G. B.

1999-12-01

Localized increase of the magnetic field observed by routine methods on the photosphere result in the growth of a number of active processes in the solar atmosphere and the heliosphere. These localized regions of increased magnetic field are called active regions (AR). The main processes of transfer, accumulation and release of energy in an AR is, however, out of scope of photospheric observations being essentially a 3D-process and happening either under photosphere or up in the corona. So, to investigate these plasma structures and processes we are bound to use either extrapolation of optical observational methods or observations in EUV, X-rays and radio. In this review, we stress and illustrate the input to the problem gained from radio astronomical methods and discuss possible future development of their applicatications. Historically speaking each new step in developing radio technique of observations resulted in detecting some new physics of ARs. The most significant progress in the last few years in radio diagnostics of the plasma structures of magnetospheres of the solar ARs is connected with the developing of the 2D full disk analysis on regular basis made at Nobeyama and detailed multichannel spectral-polarization (but one-dimensional and one per day) solar observations at the RATAN-600. In this report the bulk of attention is paid to the new approach to the study of solar activity gained with the Nobeyama radioheliograph and analyzing the ways for future progress. The most important new features of the multicomponent radio sources of the ARs studied using Nobeyama radioheliograph are as follow: 1. The analysis of magnetic field structures in solar corona above sunspot with 2000 G. Their temporal evolution and fluctuations with the periods around 3 and 5 minutes, due to MHD-waves in sunspot magnetic tubes and surrounding plasma. These investigations are certainly based on an analysis of thermal cyclotron emission of lower corona and CCTR above sunspot umbra. 2. Magnetography of the solar active regions presenting the weak magnetic fields (with the sensitivity of several G) reflecting longitude component of the magnetic field in chromosphere and corona and solar faculae structure. The method is based on an analysis of the weak polarization (of the order of 1% or less). 3. An analysis of the structure, temperature, and density of arches seen above neutral magnetic field lines (seen in most ARs with spots and without ones). 4. Study of temporal and spatial behavior of inversion of the sign of the circular polarization with the result of magnetography of the solar corona. 5. An analysis of the solar activity at high heliographic latitudes, observed mostly as polar faculae (increased brightness structures having counterparts in optical white light observations). In modern study of the solar activity analysis of the activity of polar zones are of principal importance. Nobeyama probably presents the most reliable way to study this. The above points present not exactly completed results but rather the directions for future studies. These should use full time coverage of observations at different phases of the solar activity and combination of observations with other radio, optical, EUV and X-ray observations whenever possible.

SOLAR MULTIPLE ERUPTIONS FROM A CONFINED MAGNETIC STRUCTURE

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

Lee, Jeongwoo; Chae, Jongchul; Liu, Chang

2016-09-20

How eruption can recur from a confined magnetic structure is discussed based on the Solar Dynamics Observatory observations of the NOAA active region 11444, which produced three eruptions within 1.5 hr on 2012 March 27. The active region (AR) had the positive-polarity magnetic fields in the center surrounded by the negative-polarity fields around. Since such a distribution of magnetic polarity tends to form a dome-like magnetic fan structure confined over the AR, the multiple eruptions were puzzling. Our investigation reveals that this event exhibits several properties distinct from other eruptions associated with magnetic fan structures: (i) a long filament encirclingmore » the AR was present before the eruptions; (ii) expansion of the open–closed boundary (OCB) of the field lines after each eruption was suggestive of the growing fan-dome structure, and (iii) the ribbons inside the closed magnetic polarity inversion line evolved in response to the expanding OCB. It thus appears that in spite of multiple eruptions the fan-dome structure remained undamaged, and the closing back field lines after each eruption rather reinforced the fan-dome structure. We argue that the multiple eruptions could occur in this AR in spite of its confined magnetic structure because the filament encircling the AR was adequate for slipping through the magnetic separatrix to minimize the damage to its overlying fan-dome structure. The result of this study provides a new insight into the productivity of eruptions from a confined magnetic structure.« less

WAITING TIMES OF QUASI-HOMOLOGOUS CORONAL MASS EJECTIONS FROM SUPER ACTIVE REGIONS

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

Wang Yuming; Liu Lijuan; Shen Chenglong

Why and how do some active regions (ARs) frequently produce coronal mass ejections (CMEs)? These are key questions for deepening our understanding of the mechanisms and processes of energy accumulation and sudden release in ARs and for improving our space weather prediction capability. Although some case studies have been performed, these questions are still far from fully answered. These issues are now being addressed statistically through an investigation of the waiting times of quasi-homologous CMEs from super ARs in solar cycle 23. It is found that the waiting times of quasi-homologous CMEs have a two-component distribution with a separation atmore » about 18 hr. The first component is a Gaussian-like distribution with a peak at about 7 hr, which indicates a tight physical connection between these quasi-homologous CMEs. The likelihood of two or more occurrences of CMEs faster than 1200 km s{sup -1} from the same AR within 18 hr is about 20%. Furthermore, the correlation analysis among CME waiting times, CME speeds, and CME occurrence rates reveals that these quantities are independent of each other, suggesting that the perturbation by preceding CMEs rather than free energy input is the direct cause of quasi-homologous CMEs. The peak waiting time of 7 hr probably characterizes the timescale of the growth of the instabilities triggered by preceding CMEs. This study uncovers some clues from a statistical perspective for us to understand quasi-homologous CMEs as well as CME-rich ARs.« less

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

Signatures of Slow Solar Wind Streams from Active Regions in the Inner Corona

NASA Astrophysics Data System (ADS)

Slemzin, V.; Harra, L.; Urnov, A.; Kuzin, S.; Goryaev, F.; Berghmans, D.

2013-08-01

The identification of solar-wind sources is an important question in solar physics. The existing solar-wind models ( e.g., the Wang-Sheeley-Arge model) provide the approximate locations of the solar wind sources based on magnetic field extrapolations. It has been suggested recently that plasma outflows observed at the edges of active regions may be a source of the slow solar wind. To explore this we analyze an isolated active region (AR) adjacent to small coronal hole (CH) in July/August 2009. On 1 August, Hinode/EUV Imaging Spectrometer observations showed two compact outflow regions in the corona. Coronal rays were observed above the active-region coronal hole (ARCH) region on the eastern limb on 31 July by STEREO-A/EUVI and at the western limb on 7 August by CORONAS- Photon/TESIS telescopes. In both cases the coronal rays were co-aligned with open magnetic-field lines given by the potential field source surface model, which expanded into the streamer. The solar-wind parameters measured by STEREO-B, ACE, Wind, and STEREO-A confirmed the identification of the ARCH as a source region of the slow solar wind. The results of the study support the suggestion that coronal rays can represent signatures of outflows from ARs propagating in the inner corona along open field lines into the heliosphere.

Effective Diagnosis of Alzheimer's Disease by Means of Association Rules

NASA Astrophysics Data System (ADS)

Chaves, R.; Ramírez, J.; Górriz, J. M.; López, M.; Salas-Gonzalez, D.; Illán, I.; Segovia, F.; Padilla, P.

In this paper we present a novel classification method of SPECT images for the early diagnosis of the Alzheimer's disease (AD). The proposed method is based on Association Rules (ARs) aiming to discover interesting associations between attributes contained in the database. The system uses firstly voxel-as-features (VAF) and Activation Estimation (AE) to find tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs act as inputs to secondly mining ARs between activated blocks for controls, with a specified minimum support and minimum confidence. ARs are mined in supervised mode, using information previously extracted from the most discriminant rules for centering interest in the relevant brain areas, reducing the computational requirement of the system. Finally classification process is performed depending on the number of previously mined rules verified by each subject, yielding an up to 95.87% classification accuracy, thus outperforming recent developed methods for AD diagnosis.

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

DTIC Science & Technology

2006-12-01

has fine mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task was to...construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two domains in AR

The evolution of flaring and non-flaring active regions

NASA Astrophysics Data System (ADS)

Kilcik, A.; Yurchyshyn, V.; Sahin, S.; Sarp, V.; Obridko, V.; Ozguc, A.; Rozelot, J. P.

2018-06-01

According to the modified Zurich classification, sunspot groups are classified into seven different classes (A, B, C, D, E, F and H) based on their morphology and evolution. In this classification, classes A and B, which are small groups, describe the beginning of sunspot evolution, while classes D, E and F describe the large and evolved groups. Class C describes the middle phase of sunspot evolution and the class H describes the end of sunspot evolution. Here, we compare the lifetime and temporal evolution of flaring and non-flaring active regions (ARs), and the flaring effect on ARs in these groups in detail for the last two solar cycles (1996 through 2016). Our main findings are as follows: (i) Flaring sunspot groups have longer lifetimes than non-flaring ones. (ii) Most of the class A, B and C flaring ARs rapidly evolve to higher classes, while this is not applicable for non-flaring ARs. More than 50 per cent of the flaring A, B and C groups changed morphologically, while the remaining D, E, F and H groups did not change remarkably after the flare activity. (iii) 75 per cent of all flaring sunspot groups are large and complex. (iv) There is a significant increase in the sunspot group area in classes A, B, C, D and H after flaring activity. In contrast, the sunspot group area of classes E and F decreased. The sunspot counts of classes D, E and F decreased as well, while classes A, B, C and H showed an increase.

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.

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.

Low-Latitude Solar Coronal Hole Formation

NASA Astrophysics Data System (ADS)

Haislmaier, Karl; Petrie, G.

2013-01-01

Little is known about the origin of low-latitude solar coronal holes (CHs) and their relation to the magnetic flux distribution of the underlying Solar Photosphere. Two recent reports (Karachik et al. 2010, Wang et al. 2010) suggest that CH formation might be correlated with the decay of active regions (ARs) in the photosphere. In order to explore the nature and extent of such correlations, we surveyed GONG (Global Oscillations Network Group) synoptic magnetograms and STEREO (Solar TErrestrial RElations Observatory) synoptic extreme ultraviolet images of Carrington rotations 2047-2112. From these two data sets, 41 AR-CH pairs were identified, accounting for ~34% of all ARs that appeared during the surveyed rotations. Each of these AR-CH pairs fell into one of two general classes: 1) those where the CHs were associated with the leading polarity fluxes of decaying ARs whose lagging fluxes largely decayed away, and 2) those where the CHs were associated with the lagging fluxes of surviving ARs. Perhaps surprisingly, the positive and negative fluxes of the ARs generally remained well balanced after their CHs developed. Extrapolated coronal potential-field source-surface (PFSS) models linked the CH creation and development to changes in magnetic connectivity with the surroundings as the AR flux became more diffuse over time. These considerations lead us to conclude that CHs are associated with low intensity, unipolar magnetic flux regions in the photosphere, which are most readily created by the turbulent diffusion and decay of AR flux. This work is carried out through the National Solar Observatory Research Experiences for Undergraduate (REU) site program, which is co-funded by the Department of Defense in partnership with the National Science Foundation REU Program. The National Solar Observatory is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) under cooperative agreement with the National Science Foundation.

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.

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.

Giant Sunspot Erupts with 4th Substantial Flare

NASA Image and Video Library

2017-12-08

The sun emitted a significant solar flare, peaking at 5:40 p.m. EDT on Oct. 24, 2014. The flare erupted from a particularly large active region -- labeled AR 12192 -- on the sun that is the largest in 24 years. This is the fourth substantial flare from this active region since Oct. 19. Read more: www.nasa.gov/content/goddard/giant-sunspot-erupts-with-4t...

Behavioral and genetic correlates of the neural response to infant crying among human fathers.

PubMed

Mascaro, Jennifer S; Hackett, Patrick D; Gouzoules, Harold; Lori, Adriana; Rilling, James K

2014-11-01

Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1-2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

DISTRIBUTION OF MAGNETIC BIPOLES ON THE SUN OVER THREE SOLAR CYCLES

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

Tlatov, Andrey G.; Vasil'eva, Valerya V.; Pevtsov, Alexei A., E-mail: tlatov@mail.r, E-mail: apevtsov@nso.ed

We employ synoptic full disk longitudinal magnetograms to study latitudinal distribution and orientation (tilt) of magnetic bipoles in the course of sunspot activity during cycles 21, 22, and 23. The data set includes daily observations from the National Solar Observatory at Kitt Peak (1975-2002) and Michelson Doppler Imager on board the Solar and Heliospheric Observatory (MDI/SOHO, 1996-2009). Bipole pairs were selected on the basis of proximity and flux balance of two neighboring flux elements of opposite polarity. Using the area of the bipoles, we have separated them into small quiet-Sun bipoles (QSBs), ephemeral regions (ERs), and active regions (ARs). Wemore » find that in their orientation, ERs and ARs follow Hale-Nicholson polarity rule. As expected, AR tilts follow Joy's law. ERs, however, show significantly larger tilts of opposite sign for a given hemisphere. QSBs are randomly oriented. Unlike ARs, ERs also show a preference in their orientation depending on the polarity of the large-scale magnetic field. These orientation properties may indicate that some ERs may form at or near the photosphere via the random encounter of opposite polarity elements, while others may originate in the convection zone at about the same location as ARs. The combined latitudinal distribution of ERs and ARs exhibits a clear presence of Spoerer's butterfly diagram (equatorward drift in the course of a solar cycle). ERs extend the ARs' 'wing' of the butterfly diagram to higher latitudes. This high latitude extension of ERs suggests an extended solar cycle with the first magnetic elements of the next cycle developing shortly after the maximum of the previous cycle. The polarity orientation and tilt of ERs may suggest the presence of poloidal fields of two configurations (new cycle and old cycle) in the convection zone at the declining phase of the sunspot cycle.« less

SUMER-IRIS Observations of AR11875

NASA Astrophysics Data System (ADS)

Schmit, Donald; Innes, Davina

2014-05-01

We present results of the first joint observing campaign of IRIS and SOHO/SUMER. While the IRIS datasets provide information on the chromosphere and transition region, SUMER provides complementary diagnostics on the corona. On 2013-10-24, we observed an active region, AR11875, and the surrounding plage for approximately 4 hours using rapid-cadence observing programs. These datasets include spectra from a small C -class flare which occurs in conjunction with an Ellerman-bomb type event. Our analysis focusses on how the high spatial resolution and slit jaw imaging capabilities of IRIS shed light on the unresolved structure of transient events in the SUMER catalog.

The Compound and Homologous Eruptions from the SAR 11429

NASA Astrophysics Data System (ADS)

Dhakal, Suman Kumar; Zhang, Jie

2016-05-01

Super Active Regions (SARs) are ARs which shows extremely high rate of solar eruptions. NOAA AR 11429 was a SAR which produced 47 C-Class, 15 M-Class and 3 X-Class flares and 8 CMEs during its passage from the front disk of the Sun. This SAR had anti-Hale and delta-spot magnetic configuration and many sub-regions of magnetic flux emergence. With the aid of multi-wavelength observations of the Solar Dynamics Observatory (SDO), the Solar Terrestrial Relations Observatory (STEREO) and nonlinear force-free model for the magnetic field in the solar corona, we found the existence of many magnetic flux structures (flux bundles) in the corona of the AR. The energy released by these co-existing flux bundles within short time, resulted in compound erutpions from the AR on March 9 and 10, 2012. In the period of 38 hours, after the CME eruption on March 9, the continuous shearing and cancellation and new magnetic flux emergence resulted in another CME on March 10. Both of the events showed the compound nature and the similarity of the foot-points and EUV dimming made these eruptions homologous.

Genome-Wide Analysis of Androgen Receptor Targets Reveals COUP-TF1 as a Novel Player in Human Prostate Cancer

PubMed Central

Perets, Ruth; Kaplan, Tommy; Stein, Ilan; Hidas, Guy; Tayeb, Shay; Avraham, Eti; Ben-Neriah, Yinon; Simon, Itamar; Pikarsky, Eli

2012-01-01

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR – COUP-TF1 – which could possibly play a role in human prostate cancer. PMID:23056316

Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.

PubMed

Perets, Ruth; Kaplan, Tommy; Stein, Ilan; Hidas, Guy; Tayeb, Shay; Avraham, Eti; Ben-Neriah, Yinon; Simon, Itamar; Pikarsky, Eli

2012-01-01

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR - COUP-TF1 - which could possibly play a role in human prostate cancer.

Seasonal inhomogeneity in cloud precursors over Gangetic Himalayan region during GVAX campaign

NASA Astrophysics Data System (ADS)

Dumka, U. C.; Bhattu, Deepika; Tripathi, S. N.; Kaskaoutis, D. G.; Madhavan, B. L.

2015-03-01

Atmospheric aerosols are key elements in cloud microphysics, the hydrological cycle and climate by serving as cloud condensation nuclei (CCN). The present work analyzes simultaneous measurements of number concentration of CCN (NCCN) and condensation nuclei (NCN) obtained at Nainital, in the Gangetic-Himalayan (GH) region, during the frameworks of Ganges Valley Aerosol Experiment (GVAX), June 2011 to March 2012. The NCCN, NCN and activation (AR = NCCN/NCN) at 0.31-0.33% S (supersaturation ratio), exhibit significant daily, monthly and seasonal variations within a range of 684-2065 cm- 3 for NCCN, 1606-4124 cm- 3 for NCN, and 0.38-0.60 for AR, suggesting large inhomogeneity in aerosol properties, types and sources, which control the degree of aerosol potential activation. Thus, transported aerosols from the Ganges valley and abroad, the boundary-layer dynamics and atmospheric modification processes play an important role in aerosol-cloud interactions over the GH region. The NCN and NCCN show monthly-dependent diurnal variations with afternoon maxima due to transported aerosols from the Ganges valley up to the Himalayan foothills, while the AR is lower during these hours implying lower hygroscopicities or smaller sizes of the transported aerosols. The dependence of NCCN on S is highest during Dec-Mar and lowest during monsoon (Jun-Sep), suggesting different aerosol chemical composition. Comparison between Nainital and Kanpur shows that NCN and NCCN are much lower at Nainital, while the similarity in AR suggests aerosols of similar type, source and chemical composition uplifted from the Ganges valley to the Himalayan foothills.

MAGNETIC NON-POTENTIALITY OF SOLAR ACTIVE REGIONS AND PEAK X-RAY FLUX OF THE ASSOCIATED FLARES

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

Tiwari, Sanjiv Kumar; Venkatakrishnan, P.; Gosain, Sanjay, E-mail: pvk@prl.res.i, E-mail: sgosain@prl.res.i

Predicting the severity of solar eruptive phenomena such as flares and coronal mass ejections remains a great challenge despite concerted efforts to do so over the past several decades. However, the advent of high-quality vector magnetograms obtained from Hinode (SOT/SP) has increased the possibility of meeting this challenge. In particular, the spatially averaged signed shear angle (SASSA) seems to be a unique parameter for quantifying the non-potentiality of active regions. We demonstrate the usefulness of the SASSA for predicting flare severity. For this purpose, we present case studies of the evolution of magnetic non-potentiality using 115 vector magnetograms of fourmore » active regions, namely, ARs NOAA 10930, 10960, 10961, and 10963 during 2006 December 8-15, 2007 June 3-10, 2007 June 28-July 5, and 2007 July 10-17, respectively. The NOAA ARs 10930 and 10960 were very active and produced X and M class flares, respectively, along with many smaller X-ray flares. On the other hand, the NOAA ARs 10961 and 10963 were relatively less active and produced only very small (mostly A- and B-class) flares. For this study, we have used a large number of high-resolution vector magnetograms obtained from Hinode (SOT/SP). Our analysis shows that the peak X-ray flux of the most intense solar flare emanating from the active regions depends on the magnitude of the SASSA at the time of the flare. This finding of the existence of a lower limit of the SASSA for a given class of X-ray flares will be very useful for space weather forecasting. We have also studied another non-potentiality parameter called the mean weighted shear angle (MWSA) of the vector magnetograms along with the SASSA. We find that the MWSA does not show such distinction as the SASSA for upper limits of the GOES X-ray flux of solar flares; however, both the quantities show similar trends during the evolution of all active regions studied.« less

Physical Characteristics of AR 11024 Plasma Based on SPHINX and XRT Data

NASA Astrophysics Data System (ADS)

Sylwester, B.; Sylwester, J.; Siarkowski, M.; Engell, A. J.; Kuzin, S. V.

We have studied the evolution of basic physical properties of plasma within the coronal part of the isolated, new cycle region (AR 11024) during its crossing over the solar disc in July 2009. Our analysis is based on the high temporal and spectral resolution measurements performed by the Polish X-ray spectrometer SphinX onboard the CORONAS-Photon satellite. Hinode XRT images provide information on spatial extension of the emission within this active region. It is found that the average temperature of the plasma within the analysed region is the highest (˜6 MK) when the region is young and gradually declines to ˜2 MK when the emission measure is the highest. An average density during this first part of the evolution is estimated to be ˜2 x 10^9 cm^{-3}.

PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion

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

Zhang, Zheng; Jin, Bo; Jin, Yaqiong

Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that themore » PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the −851 to −836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis. - Highlights: • Androgen treatment of LNCaP cells induced PTTG1 expression. • Knockdown of PTTG1 expression significantly reduced androgen-induced LNCaP cell growth and invasion. • PTTG1 is highly expressed in metastasis prostate cancer tissue. • PTTG1 is a novel downstream target gene of androgen receptor.« less

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.

Use of dissolved and vapor‐phase gases to investigate methanogenic degradation of petroleum hydrocarbon contamination in the subsurface

USGS Publications Warehouse

Amos, Richard T.; Mayer, K. Ulrich; Bekins, Barbara A.; Delin, Geoffrey N.; Williams, Randi L.

2005-01-01

At many sites contaminated with petroleum hydrocarbons, methanogenesis is a significant degradation pathway. Techniques to estimate CH4 production, consumption, and transport processes are needed to understand the geochemical system, provide a complete carbon mass balance, and quantify the hydrocarbon degradation rate. Dissolved and vapor‐phase gas data collected at a petroleum hydrocarbon contaminated site near Bemidji, Minnesota, demonstrate that naturally occurring nonreactive or relatively inert gases such as Ar and N2 can be effectively used to better understand and quantify physical and chemical processes related to methanogenic activity in the subsurface. In the vadose zone, regions of Ar and N2 depletion and enrichment are indicative of methanogenic and methanotrophic zones, and concentration gradients between the regions suggest that reaction‐induced advection can be an important gas transport process. In the saturated zone, dissolved Ar and N2 concentrations are used to quantify degassing driven by methanogenesis and also suggest that attenuation of methane along the flow path, into the downgradient aquifer, is largely controlled by physical processes. Slight but discernable preferential depletion of N2 over Ar, in both the saturated and unsaturated zones near the free‐phase oil, suggests reactivity of N2 and is consistent with other evidence indicating that nitrogen fixation by microbial activity is taking place at this site.

The three-dimensional angular widths of CMEs and their relations to the source regions

NASA Astrophysics Data System (ADS)

Zhao, X.; Feng, X. S.

2017-12-01

The angular width of a coronal mass ejection (CME) is an important factor to determine whether the corresponding interplanetary CME (ICME) and its preceding shock will reach our Earth. However, very few studies are involved to study the decisive factors of the CME's angular width. In this study, we use the three-dimensional (3D) angular width of CMEs obtained from the Graduated Cylindrical Shell (GCS) model based on observations of Solar Terrestrial Relations Observatory (STEREO) to study the relations between the CME's 3D width and characteristics of the CME's source region. We find that for the CMEs produced by active regions (ARs), the CME width has some correlations with the AR's area and flux, but these correlations are not strong. The magnetic flux contained in the CME seems to come from only part of the AR's total flux. For the CMEs produced by flare regions, the correlations between the CME angular width and the flare region's area and flux are strong. The magnetic flux within those CMEs seems to totally (even not enough) come from the flare region. Our findings prefer to support that the CME's 3D angular width can be generally estimated based on observations of Solar Dynamics Observatory (SDO) for its source region instead of the observations from coronagraphs onboard Solar and Heliospheric Observatory (SOHO) and STEREO.

DIFFRACTION, REFRACTION, AND REFLECTION OF AN EXTREME-ULTRAVIOLET WAVE OBSERVED DURING ITS INTERACTIONS WITH REMOTE ACTIVE REGIONS

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

Shen Yuandeng; Liu Yu; Zhao Ruijuan

2013-08-20

We present observations of the diffraction, refraction, and reflection of a global extreme-ultraviolet (EUV) wave propagating in the solar corona. These intriguing phenomena are observed when the wave interacts with two remote active regions, and together they exhibit properties of an EUV wave. When the wave approached AR11465, it became weaker and finally disappeared in the active region, but a few minutes later a new wavefront appeared behind the active region, and it was not concentric with the incoming wave. In addition, a reflected wave was also simultaneously observed on the wave incoming side. When the wave approached AR11459, itmore » transmitted through the active region directly and without reflection. The formation of the new wavefront and the transmission could be explained with diffraction and refraction effects, respectively. We propose that the different behaviors observed during the interactions may be caused by different speed gradients at the boundaries of the two active regions. We find that the EUV wave formed ahead of a group of expanding loops a few minutes after the start of the loops' expansion, which represents the initiation of the associated coronal mass ejection (CME). Based on these results, we conclude that the EUV wave should be a nonlinear magnetosonic wave or shock driven by the associated CME, which propagated faster than the ambient fast mode speed and gradually slowed down to an ordinary linear wave. Our observations support the hybrid model that includes both fast wave and slow non-wave components.« less

Mechanisms of protein kinase C signaling in the modulation of 3',5'-cyclic adenosine monophosphate-mediated steroidogenesis in mouse gonadal cells.

PubMed

Manna, Pulak R; Huhtaniemi, Ilpo T; Stocco, Douglas M

2009-07-01

The protein kinase C (PKC) signaling pathway plays integral roles in the expression of the steroidogenic acute regulatory (StAR) protein that regulates steroid biosynthesis in steroidogenic cells. PKC can modulate the activity of cAMP/protein kinase A signaling involved in steroidogenesis; however, its mechanism remains obscure. In the present study, we demonstrate that activation of the PKC pathway, by phorbol 12-myristate 13-acetate (PMA), was capable of potentiating dibutyryl cAMP [(Bu)(2)cAMP]-stimulated StAR expression, StAR phosphorylation, and progesterone synthesis in both mouse Leydig (MA-10) and granulosa (KK-1) tumor cells. The steroidogenic potential of PMA and (Bu)(2)cAMP was linked with phosphorylation of ERK 1/2; however, inhibition of the latter demonstrated varying effects on steroidogenesis. Transcriptional activation of the StAR gene by PMA and (Bu)(2)cAMP was influenced by several factors, its up-regulation being dependent on phosphorylation of the cAMP response element binding protein (CREB). An oligonucleotide probe containing a CREB/activating transcription factor binding region in the StAR promoter was found to bind nuclear proteins in PMA and (Bu)(2)cAMP-treated MA-10 and KK-1 cells. Chromatin immunoprecipitation studies revealed that the induction of phosphorylated CREB was tightly correlated with in vivo protein-DNA interactions and recruitment of CREB binding protein to the StAR promoter. Ectopic expression of CREB binding protein enhanced CREB-mediated transcription of the StAR gene, an event that was markedly repressed by the adenovirus E1A oncoprotein. Further studies demonstrated that the activation of StAR expression and steroid synthesis by PMA and (Bu)(2)cAMP was associated with expression of the nuclear receptor Nur77, indicating its essential role in hormone-regulated steroidogenesis. Collectively, these findings provide insight into the mechanisms by which PKC modulates cAMP/protein kinase A responsiveness involved in regulating the steroidogenic response in mouse gonadal cells.

Parametric modulation of neural activity during face emotion processing in unaffected youth at familial risk for bipolar disorder.

PubMed

Brotman, Melissa A; Deveney, Christen M; Thomas, Laura A; Hinton, Kendra E; Yi, Jennifer Y; Pine, Daniel S; Leibenluft, Ellen

2014-11-01

Both patients with pediatric bipolar disorder (BD) and unaffected youth at familial risk (AR) for the illness show impairments in face emotion labeling. Few studies, however, have examined brain regions engaged in AR youth when processing emotional faces. Moreover, studies have yet to explore neural responsiveness to subtle changes in face emotion in AR youth. Sixty-four unrelated youth, including 20 patients with BD, 15 unaffected AR youth, and 29 healthy comparisons (HC), completed functional magnetic resonance imaging. Neutral faces were morphed with angry or happy faces in 25% intervals. In specific phases of the task, youth alternatively made explicit (hostility) or implicit (nose width) ratings of the faces. The slope of blood oxygenated level-dependent activity was calculated across neutral to angry and neutral to happy face stimuli. Behaviorally, both subjects with BD (p ≤ 0.001) and AR youth (p ≤ 0.05) rated faces as less hostile relative to HC. Consistent with this, in response to increasing anger on the face, patients with BD and AR youth showed decreased modulation in the amygdala and inferior frontal gyrus (IFG; BA 46) compared to HC (all p ≤ 0.05). Amygdala dysfunction was present across both implicit and explicit rating conditions, but IFG modulation deficits were specific to the explicit condition. With increasing happiness, AR youth showed aberrant modulation in the IFG, which was also sensitive to task demands (all p ≤ 0.05). Decreased amygdala and IFG modulation in patients with BD and AR youth may be pathophysiological risk markers for BD, and may underlie the social cognition and face emotion labeling deficits observed in BD and AR youth. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Ralstonia solanacearum novel E3 ubiquitin ligase (NEL) effectors RipAW and RipAR suppress pattern-triggered immunity in plants.

PubMed

Nakano, Masahito; Oda, Kenji; Mukaihara, Takafumi

2017-07-01

Ralstonia solanacearum is the causal agent of bacterial wilt in solanaceous crops. This pathogen injects more than 70 effector proteins into host plant cells via the Hrp type III secretion system to cause a successful infection. However, the function of these effectors in plant cells, especially in the suppression of plant immunity, remains largely unknown. In this study, we characterized two Ralstonia solanacearum effectors, RipAW and RipAR, which share homology with the IpaH family of effectors from animal and plant pathogenic bacteria, that have a novel E3 ubiquitin ligase (NEL) domain. Recombinant RipAW and RipAR show E3 ubiquitin ligase activity in vitro. RipAW and RipAR localized to the cytoplasm of plant cells and significantly suppressed pattern-triggered immunity (PTI) responses such as the production of reactive oxygen species and the expression of defence-related genes when expressed in leaves of Nicotiana benthamiana. Mutation in the conserved cysteine residue in the NEL domain of RipAW completely abolished the E3 ubiquitin ligase activity in vitro and the ability to suppress PTI responses in plant leaves. These results indicate that RipAW suppresses plant PTI responses through the E3 ubiquitin ligase activity. Unlike other members of the IpaH family of effectors, RipAW and RipAR had no leucine-rich repeat motifs in their amino acid sequences. A conserved C-terminal region of RipAW is indispensable for PTI suppression. Transgenic Arabidopsis plants expressing RipAW and RipAR showed increased disease susceptibility, suggesting that RipAW and RipAR contribute to bacterial virulence in plants.

A Combined Proteomic and Transcriptomic Analysis on Sulfur Metabolism Pathways of Arabidopsis thaliana under Simulated Acid Rain

PubMed Central

Wang, Wenhua; Simon, Martin; Wu, Feihua; Hu, Wenjun; Chen, Juan B.; Zheng, Hailei

2014-01-01

With rapid economic development, most regions in southern China have suffered acid rain (AR) pollution. In our study, we analyzed the changes in sulfur metabolism in Arabidopsis under simulated AR stress which provide one of the first case studies, in which the systematic responses in sulfur metabolism were characterized by high-throughput methods at different levels including proteomic, genomic and physiological approaches. Generally, we found that all of the processes related to sulfur metabolism responded to AR stress, including sulfur uptake, activation and also synthesis of sulfur-containing amino acid and other secondary metabolites. Finally, we provided a catalogue of the detected sulfur metabolic changes and reconstructed the coordinating network of their mutual influences. This study can help us to understand the mechanisms of plants to adapt to AR stress. PMID:24595051

ON THE INJECTION OF HELICITY BY THE SHEARING MOTION OF FLUXES IN RELATION TO FLARES AND CORONAL MASS EJECTIONS

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

Vemareddy, P.; Ambastha, A.; Maurya, R. A.

An investigation of helicity injection by photospheric shear motions is carried out for two active regions (ARs), NOAA 11158 and 11166, using line-of-sight magnetic field observations obtained from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory. We derived the horizontal velocities in the ARs from the differential affine velocity estimator (DAVE) technique. Persistent strong shear motions at maximum velocities in the range of 0.6-0.9 km s{sup -1} along the magnetic polarity inversion line and outward flows from the peripheral regions of the sunspots were observed in the two ARs. The helicities injected in NOAA 11158 and 11166more » during their six-day evolution period were estimated as 14.16 Multiplication-Sign 10{sup 42} Mx{sup 2} and 9.5 Multiplication-Sign 10{sup 42} Mx{sup 2}, respectively. The estimated injection rates decreased up to 13% by increasing the time interval between the magnetograms from 12 minutes to 36 minutes, and increased up to 9% by decreasing the DAVE window size from 21 Multiplication-Sign 18 to 9 Multiplication-Sign 6 pixel{sup 2}, resulting in 10% variation in the accumulated helicity. In both ARs, the flare-prone regions (R2) had inhomogeneous helicity flux distribution with mixed helicities of both signs and coronal mass ejection (CME) prone regions had almost homogeneous distribution of helicity flux dominated by a single sign. The temporal profiles of helicity injection showed impulsive variations during some flares/CMEs due to negative helicity injection into the dominant region of positive helicity flux. A quantitative analysis reveals a marginally significant association of helicity flux with CMEs but not flares in AR 11158, while for the AR 11166, we find a marginally significant association of helicity flux with flares but not CMEs, providing evidence of the role of helicity injection at localized sites of the events. These short-term variations of helicity flux are further discussed in view of possible flare-related effects. This study suggests that flux motions and spatial distribution of helicity injection are important to understanding the complex nature of the magnetic flux system of the AR, and how it can lead to conditions favorable for eruptive events.« less

Non-neutralized Electric Currents in Solar Active Regions and Flare Productivity

NASA Astrophysics Data System (ADS)

Kontogiannis, Ioannis; Georgoulis, Manolis K.; Park, Sung-Hong; Guerra, Jordan A.

2017-11-01

We explore the association of non-neutralized currents with solar flare occurrence in a sizable sample of observations, aiming to show the potential of such currents in solar flare prediction. We used the high-quality vector magnetograms that are regularly produced by the Helioseismic Magnetic Imager, and more specifically, the Space weather HMI Active Region Patches (SHARP). Through a newly established method that incorporates detailed error analysis, we calculated the non-neutralized currents contained in active regions (AR). Two predictors were produced, namely the total and the maximum unsigned non-neutralized current. Both were tested in AR time-series and a representative sample of point-in-time observations during the interval 2012 - 2016. The average values of non-neutralized currents in flaring active regions are higher by more than an order of magnitude than in non-flaring regions and correlate very well with the corresponding flare index. The temporal evolution of these parameters appears to be connected to physical processes, such as flux emergence and/or magnetic polarity inversion line formation, that are associated with increased solar flare activity. Using Bayesian inference of flaring probabilities, we show that the total unsigned non-neutralized current significantly outperforms the total unsigned magnetic flux and other well-established current-related predictors. It therefore shows good prospects for inclusion in an operational flare-forecasting service. We plan to use the new predictor in the framework of the FLARECAST project along with other highly performing predictors.

HARPs: Tracked Active Region Patch Data Product from SDO/HMI

NASA Astrophysics Data System (ADS)

Turmon, M.; Hoeksema, J. T.; Sun, X.; Bobra, M.

2012-12-01

We describe an HMI data product consisting of tracked magnetic features on the scale of solar active regions, abbreviated HARPs (HMI Active Region Patches). The HARP data series has been helpful for subsetting individual active regions, for development of near-real-time (NRT) space weather indices for individual active regions, and for defining closed magnetic structures for computationally-intensive algorithms like vector field disambiguation. The data series builds upon the 720s cadence activity masks, which identify large-scale instantaneously-observed magnetic features. Using these masks as a starting point, large spatially-coherent structures are identified using convolution with a longitudinally-extended kernel on a spherical domain. The resulting set of identified regions is then tracked from image to image. The metric for inter-image association is area of overlap between the best current estimate of AR location, as predicted by temporally extrapolating each currently tracked object, and the set of instantaneously-observed magnetic structures. Once completed tracks have been extracted, they are made into a standardized HARP data series by finding the smallest constant-angular-velocity box, of constant width in latitude and longitude, that encompasses all appearances of the active region. This data product is currently available, in definitive and near-real-time forms, with accompanying region-strength, location, and NOAA-AR metadata, on HMI's Joint Science Operations Center (JSOC) data portal.; HARP outlines for three days (2001 February 14, 15, and 16, 00:00 TAI, flipped N-S, selected from the 12-minute cadence original data product). HARPs are shown in the same color (some colors repeated) with a thin white box surrounding each HARP. HARPs are tracked and associated from image to image. HARPs, such as the yellow one in the images above, need not be connected regions. Merges and splits, such as the light blue region, are accounted for automatically.

Cloning, expression, cellular distribution, and role in chemotaxis of a C5a receptor in rainbow trout: the first identification of a C5a receptor in a nonmammalian species

USGS Publications Warehouse

Boshra, Hani; Li, Jun; Peters, Rodney; Hansen, John; Matlapudi, Anjan; Sunyer, J. Oriol

2004-01-01

C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.

What Produce Energetic Flares with X-Shaped Ribbons on the Outskirts of Solar Active Region?

NASA Astrophysics Data System (ADS)

Liu, Rui; Chen, Jun; Wang, Yuming; Kailiu

2016-10-01

Typical solar flares display two quasi-parallel, bright ribbons on the chromosphere. In between is the polarity inversion line separating concentrated magnetic fluxes of opposite polarities in active regions (ARs). Intriguingly a series of flares exhibiting X-shaped ribbons occur at the similar location on the outskirts of NOAA AR 11967, where magnetic fluxes are scattered, yet three of them are alarmingly energetic. The X shape is similar in UV/EUV with hard X-ray emission projected in the center, which cannot be accommodated in the standard flare model. Mapping out magnetic connectivities in potential fields, we found that the X morphology is dictated by the intersection of two quasi-separatrix layers, i.e., a hyperbolic flux tube (HFT), within which a separator connecting a double null is embedded. This topology is not purely local but regulated by fluxes and flows over the whole AR. The nonlinear force-free field model suggests the formation of a current layer at the HFT, where the current dissipation can be mapped to the X-shaped ribbons via field-aligned heat conduction. These results highlight the critical role of structural skeletons in 3D magnetic reconnection.

Explorations of electric current system in solar active regions. I - Empirical inferences of the current flows

NASA Technical Reports Server (NTRS)

Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.; Liu, X. P.

1987-01-01

Techniques to identify sources of electric current systems and their channels of flow in solar active regions are explored. Measured photospheric vector magnetic fields together with high-resolution white-light and H-alpha filtergrams provide the data base to derive the current systems in the photosphere and chromosphere. As an example, the techniques are then applied to infer current systems in AR 2372 in early April 1980.

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.

Determination of coronal magnetic fields from vector magnetograms

NASA Technical Reports Server (NTRS)

Mikic, Zoran

1992-01-01

The determination of coronal magnetic fields from vector magnetograms, including the development and application of algorithms to determine force-free coronal fields above selected observations of active regions is studied. Two additional active regions were selected and analyzed. The restriction of periodicity in the 3-D code which is used to determine the coronal field was removed giving the new code variable mesh spacing and is thus able to provide a more realistic description of coronal fields. The NOAA active region AR5747 of 20 Oct. 1989 was studied. A brief account of progress during the research performed is reported.

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

Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens

PubMed Central

Lazarus, Michael; Shen, Hai-Ying; Cherasse, Yoan; Qu, Wei-Min; Huang, Zhi-Li; Bass, Caroline E.; Winsky-Sommerer, Raphaelle; Semba, Kazue; Fredholm, Bertil B.; Boison, Detlev; Hayaishi, Osamu; Urade, Yoshihiro; Chen, Jiang-Fan

2011-01-01

Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A2A receptors (A2ARs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A2ARs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A2ARs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A2ARs were focally removed from the NAc core or other A2AR-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain. PMID:21734299

Empirical algorithms to predict aragonite saturation state

NASA Astrophysics Data System (ADS)

Turk, Daniela; Dowd, Michael

2017-04-01

Novel sensor packages deployed on autonomous platforms (Profiling Floats, Gliders, Moorings, SeaCycler) and biogeochemical models have a potential to increase the coverage of a key water chemistry variable, aragonite saturation state (ΩAr) in time and space, in particular in the under sampled regions of global ocean. However, these do not provide the set of inorganic carbon measurements commonly used to derive ΩAr. There is therefore a need to develop regional predictive models to determine ΩAr from measurements of commonly observed or/and non carbonate oceanic variables. Here, we investigate predictive skill of several commonly observed oceanographic variables (temperature, salinity, oxygen, nitrate, phosphate and silicate) in determining ΩAr using climatology and shipboard data. This will allow us to assess potential for autonomous sensors and biogeochemical models to monitor ΩAr regionally and globally. We apply the regression models to several time series data sets and discuss regional differences and their implications for global estimates of ΩAr.

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

Baker, D.; Van Driel-Gesztelyi, L.; Green, L. M.

Using spectra obtained by the EUV Imaging Spectrometer (EIS) instrument onboard Hinode, we present a detailed spatially resolved abundance map of an active region (AR)-coronal hole (CH) complex that covers an area of 359'' × 485''. The abundance map provides first ionization potential (FIP) bias levels in various coronal structures within the large EIS field of view. Overall, FIP bias in the small, relatively young AR is 2-3. This modest FIP bias is a consequence of the age of the AR, its weak heating, and its partial reconnection with the surrounding CH. Plasma with a coronal composition is concentrated atmore » AR loop footpoints, close to where fractionation is believed to take place in the chromosphere. In the AR, we found a moderate positive correlation of FIP bias with nonthermal velocity and magnetic flux density, both of which are also strongest at the AR loop footpoints. Pathways of slightly enhanced FIP bias are traced along some of the loops connecting opposite polarities within the AR. We interpret the traces of enhanced FIP bias along these loops to be the beginning of fractionated plasma mixing in the loops. Low FIP bias in a sigmoidal channel above the AR's main polarity inversion line, where ongoing flux cancellation is taking place, provides new evidence of a bald patch magnetic topology of a sigmoid/flux rope configuration.« less

Thermal imaging of high power diode lasers subject to back-irradiance

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

Li, C.; Pipe, K. P.; Cao, C.

In this study, CCD-based thermoreflectance imaging and finite element modeling are used to study the two-dimensional (2D) temperature profile of a junction-down broad-area diode laser facet subject to back-irradiance. By determining the temperature rise in the active region (ΔΤAR) at different diode laser optical powers, back-irradiance reflectance levels, and back-irradiance spot locations, we find that ΔΤAR increases by nearly a factor of three when the back-irradiance spot is centered in the absorbing substrate approximately 5 μm away from the active region, a distance roughly equal to half of the back-irradiance spot FWHM (9 μm). This corroborates prior work studying themore » relationship between the back-irradiance spot location and catastrophic optical damage, suggesting a strong thermal basis for reduced laser lifetime in the presence of back-irradiance for diode lasers fabricated on absorbing substrates.« less

Modelling nanoflares in active regions and implications for coronal heating mechanisms

PubMed Central

Cargill, P. J.; Warren, H. P.; Bradshaw, S. J.

2015-01-01

Recent observations from the Hinode and Solar Dynamics Observatory spacecraft have provided major advances in understanding the heating of solar active regions (ARs). For ARs comprising many magnetic strands or sub-loops heated by small, impulsive events (nanoflares), it is suggested that (i) the time between individual nanoflares in a magnetic strand is 500–2000 s, (ii) a weak ‘hot’ component (more than 106.6 K) is present, and (iii) nanoflare energies may be as low as a few 1023 ergs. These imply small heating events in a stressed coronal magnetic field, where the time between individual nanoflares on a strand is of order the cooling time. Modelling suggests that the observed properties are incompatible with nanoflare models that require long energy build-up (over 10 s of thousands of seconds) and with steady heating. PMID:25897093

CME productivity associated with Solar Flare peak X-ray emission flux

NASA Astrophysics Data System (ADS)

Suryanarayana, G. S.; Balakrishna, K. M.

2018-05-01

It is often noticed that the occurrence rate of Coronal Mass Ejections (CMEs) increases with increase in flare duration where peak flux too increase. However, there is no complete association between the duration and peak flux. Distinct characteristics have been reported for active regions (ARs) where flares and CMEs occur in contrast to ARs where flares alone occur. It is observed that peak flux of flares is higher when associated with CMEs compared to peak flux of flares with which CMEs are not associated. In other words, it is likely that flare duration and peak flux are independently affected by distinct active region dynamics. Hence, we examine the relative ability of flare duration and peak flux in enhancing the CME productivity. We report that CME productivity is distinctly higher in association with the enhancement of flare peak flux in comparison to corresponding enhancement of flare duration.

Thermal imaging of high power diode lasers subject to back-irradiance

DOE PAGES

Li, C.; Pipe, K. P.; Cao, C.; ...

2018-03-07

In this study, CCD-based thermoreflectance imaging and finite element modeling are used to study the two-dimensional (2D) temperature profile of a junction-down broad-area diode laser facet subject to back-irradiance. By determining the temperature rise in the active region (ΔΤAR) at different diode laser optical powers, back-irradiance reflectance levels, and back-irradiance spot locations, we find that ΔΤAR increases by nearly a factor of three when the back-irradiance spot is centered in the absorbing substrate approximately 5 μm away from the active region, a distance roughly equal to half of the back-irradiance spot FWHM (9 μm). This corroborates prior work studying themore » relationship between the back-irradiance spot location and catastrophic optical damage, suggesting a strong thermal basis for reduced laser lifetime in the presence of back-irradiance for diode lasers fabricated on absorbing substrates.« less

Thermal imaging of high power diode lasers subject to back-irradiance

NASA Astrophysics Data System (ADS)

Li, C.; Pipe, K. P.; Cao, C.; Thiagarajan, P.; Deri, R. J.; Leisher, P. O.

2018-03-01

CCD-based thermoreflectance imaging and finite element modeling are used to study the two-dimensional (2D) temperature profile of a junction-down broad-area diode laser facet subject to back-irradiance. By determining the temperature rise in the active region (ΔΤAR) at different diode laser optical powers, back-irradiance reflectance levels, and back-irradiance spot locations, we find that ΔΤAR increases by nearly a factor of three when the back-irradiance spot is centered in the absorbing substrate approximately 5 μm away from the active region, a distance roughly equal to half of the back-irradiance spot FWHM (9 μm). This corroborates prior work studying the relationship between the back-irradiance spot location and catastrophic optical damage, suggesting a strong thermal basis for reduced laser lifetime in the presence of back-irradiance for diode lasers fabricated on absorbing substrates.

MODELING STATISTICAL PROPERTIES OF SOLAR ACTIVE REGIONS THROUGH DIRECT NUMERICAL SIMULATIONS OF 3D-MHD TURBULENCE

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

Malapaka, Shiva Kumar; Mueller, Wolf-Christian

Statistical properties of the Sun's photospheric turbulent magnetic field, especially those of the active regions (ARs), have been studied using the line-of-sight data from magnetograms taken by the Solar and Heliospheric Observatory and several other instruments. This includes structure functions and their exponents, flatness curves, and correlation functions. In these works, the dependence of structure function exponents ({zeta}{sub p}) of the order of the structure functions (p) was modeled using a non-intermittent K41 model. It is now well known that the ARs are highly turbulent and are associated with strong intermittent events. In this paper, we compare some of themore » observations from Abramenko et al. with the log-Poisson model used for modeling intermittent MHD turbulent flows. Next, we analyze the structure function data obtained from the direct numerical simulations (DNS) of homogeneous, incompressible 3D-MHD turbulence in three cases: sustained by forcing, freely decaying, and a flow initially driven and later allowed to decay (case 3). The respective DNS replicate the properties seen in the plots of {zeta}{sub p} against p of ARs. We also reproduce the trends and changes observed in intermittency in flatness and correlation functions of ARs. It is suggested from this analysis that an AR in the onset phase of a flare can be treated as a forced 3D-MHD turbulent system in its simplest form and that the flaring stage is representative of decaying 3D-MHD turbulence. It is also inferred that significant changes in intermittency from the initial onset phase of a flare to its final peak flaring phase are related to the time taken by the system to reach the initial onset phase.« less

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats.

PubMed

Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

2013-12-01

Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long-term depression (LTD) and depotentiation (DP) by low-frequency stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS-dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity-dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity.

PubMed

Hilzendeger, Aline M; Morgan, Donald A; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D; Mark, Allyn L

2012-07-15

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs. AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

INITIATION AND ERUPTION PROCESS OF MAGNETIC FLUX ROPE FROM SOLAR ACTIVE REGION NOAA 11719 TO EARTH-DIRECTED CME

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

Vemareddy, P.; Zhang, J., E-mail: vema@prl.res.in

An eruption event launched from the solar active region (AR) NOAA 11719 is investigated based on coronal EUV observations and photospheric magnetic field measurements obtained from the Solar Dynamic Observatory. The AR consists of a filament channel originating from a major sunspot and its south section is associated with an inverse-S sigmoidal system as observed in Atmospheric Imaging Assembly passbands. We regard the sigmoid as the main body of the flux rope (FR). There also exists a twisted flux bundle crossing over this FR. This overlying flux bundle transforms in shape similar to kink-rise evolution, which corresponds with the risemore » motion of the FR. The emission measure and temperature along the FR exhibits an increasing trend with its rising motion, indicating reconnection in the thinning current sheet underneath the FR. Net magnetic flux of the AR, evaluated at north and south polarities, showed decreasing behavior whereas the net current in these fluxes exhibits an increasing trend. Because the negative (positive) flux has a dominant positive (negative) current, the chirality of AR flux system is likely negative (left handed) in order to be consistent with the chirality of inverse S-sigmoidal FR. This analysis of magnetic fields of the source AR suggests that the cancelling fluxes are prime factors of the monotonous twisting of the FR system, reaching to a critical state to trigger kink instability and rise motion. This rise motion may have led to the onset of the torus instability, resulting in an Earth-directed coronal mass ejection, and the progressive reconnection in the thinning current sheet beneath the rising FR led to the M6.5 flare.« less

40Ar-39Ar Age Constraints on Volcanism and Tectonism in the Terror Rift of the Ross Sea, Antarctica

USGS Publications Warehouse

2007-01-01

Volcanic sills and dikes inferred from seismic reflection profiles and geophysical studies of the Ross Sea are thought to be related to the rift basins in the region, and their emplacement to be coeval with extension. However, lack of precise geochronology in the Terror Rift of the Ross Sea region has left these inferred relationships poorly constrained and has hindered neotectonic studies, because of the large temporal gaps between seismic reflectors of known ages. New 40Ar/39Ar geochronology presented here for submarine volcanic rocks provides better age constraints for neotectonic interpretations within the Terror Rift. Several samples from seamounts yielded young ages between 156 ± 21 and 122 ± 26 Ka. These ages support interpretations that extension within the Terror Rift was active at least through the Pleistocene. Three evenly spaced samples from the lowermost 100 m of Franklin Island range in age from 3.28 ± 0.04 to 3.73 ± 0.05 Ma. These age determinations demonstrate that construction of a small volcanic edifice such as Franklin Island took at least several hundred thousand years, and therefore that much larger ones in the Erebus Volcanic Province are likely to have taken considerably longer than previously inferred. This warrants caution in applying a limited number of age determinations to define the absolute ages of events in the Ross Sea region

Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

PubMed

Hillman, Kristin L; Doze, Van A; Porter, James E

2005-08-01

Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists indicates that beta2-AR activation is mediating the increased AP frequency. Knowledge of functional AR expression in CA1 pyramidal neurons will aid future long-term potentiation studies by allowing selective manipulation of specific beta-AR subtypes.

Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens

PubMed Central

Stedtfeld, Robert D.; Williams, Maggie R.; Fakher, Umama; Johnson, Timothy A.; Stedtfeld, Tiffany M.; Wang, Fang; Khalife, Walid T.; Hughes, Mary; Etchebarne, Brett E.; Tiedje, James M.; Hashsham, Syed A.

2016-01-01

An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities. PMID:26850162

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

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.

A Survey of Nanoflare Properties in Active Regions Observed with the Solar Dynamics Observatory

NASA Technical Reports Server (NTRS)

Viall, Nicholeen M.; Klimchuk, James A.

2017-01-01

In this paper, we examine 15 different active regions (ARs) observed with the Solar Dynamics Observatory and analyze their nanoflare properties. We have recently developed a technique that systematically identifies and measures plasma temperature dynamics by computing time lags between light curves. The time lag method tests whether the plasma is maintained at a steady temperature, or if it is dynamic, undergoing heating and cooling cycles. An important aspect of our technique is that it analyzes both observationally distinct coronal loops as well as the much more prevalent diffuse emission between them. We find that the widespread cooling reported previously for NOAA AR 11082 is a generic property of all ARs. The results are consistent with impulsive nanoflare heating followed by slower cooling. Only occasionally, however, is there full cooling from above 7 megakelvins to well below 1 megakelvin. More often, the plasma cools to approximately 1-2 megakelvins before being reheated by another nanoflare. These same 15 ARs were first studied by Warren et al. We find that the degree of cooling is not well correlated with the reported slopes of the mission measure distribution. We also conclude that the Fe (sup XVIII)-emitting plasma that they measured is mostly in a state of cooling. These results support the idea that nanoflares have a distribution of energies and frequencies, with the average delay between successive events on an individual flux tube being comparable to the plasma cooling timescale.

A Survey of Nanoflare Properties in Active Regions Observed with the Solar Dynamics Observatory

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

Viall, Nicholeen M.; Klimchuk, James A.

In this paper, we examine 15 different active regions (ARs) observed with the Solar Dynamics Observatory and analyze their nanoflare properties. We have recently developed a technique that systematically identifies and measures plasma temperature dynamics by computing time lags between light curves. The time lag method tests whether the plasma is maintained at a steady temperature, or if it is dynamic, undergoing heating and cooling cycles. An important aspect of our technique is that it analyzes both observationally distinct coronal loops as well as the much more prevalent diffuse emission between them. We find that the widespread cooling reported previouslymore » for NOAA AR 11082 is a generic property of all ARs. The results are consistent with impulsive nanoflare heating followed by slower cooling. Only occasionally, however, is there full cooling from above 7 MK to well below 1 MK. More often, the plasma cools to approximately 1–2 MK before being reheated by another nanoflare. These same 15 ARs were first studied by Warren et al. We find that the degree of cooling is not well correlated with the reported slopes of the emission measure distribution. We also conclude that the Fe xviii emitting plasma that they measured is mostly in a state of cooling. These results support the idea that nanoflares have a distribution of energies and frequencies, with the average delay between successive events on an individual flux tube being comparable to the plasma cooling timescale.« less

Management of accidental exposure to HIV: the COREVIH 2011 activity report.

PubMed

Rouveix, E; Bouvet, E; Vernat, F; Chansombat, M; Hamet, G; Pellissier, G

2014-03-01

Post-exposure prophylaxis (PEP) relies on procedures allowing quick access to treatment in case of accidental exposure to viral risk (AEV). Occupational blood exposure (OBE) affects mainly caregivers; these accidents are monitored and assessed by the inter-regional center for nosocomial infections (C-CLIN), occupational physicians, and infection control units. They are classified apart from sexual exposure for which there is currently no monitoring. Data was extracted from the COREVIH (steering committee for the prevention of HIV infection) 2011 activity reports (AR), available online. Data collection was performed using a standardized grid. Twenty-four out of 28 AR were available online. Nine thousand nine hundred and twenty AEV were reported, 44% of OBE, and 56% of sexual and other exposures. PEP was prescribed in 8% of OBE and in 77% of sexual exposures. The type of PEP was documented in 52% of the cases. Follow-up was poorly documented. AR provide an incomplete and heterogeneous review of exposure management without any standardized data collection. The difficulties encountered in data collection and monitoring are due to differences in care centers (complex patient circuits, multiple actors) and lack of common dedicated software. Sexual exposures account for 50% of AEV and most are treated; but they are incompletely reported and consequently not analyzed at the regional or national level. A typical AR collection grid is being studied in 2 COREVIH, with the objective to improve collection and obtain useful national data. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Nasal allergies in the Middle Eastern population: results from the "Allergies in Middle East Survey".

PubMed

Abdulrahman, Hussain; Hadi, Usamah; Tarraf, Hisham; Gharagozlou, Mohammad; Kamel, Mohamed; Soliman, Alaa; Hamad, Walid Abou; Hanna, Kamal Maurice; Mostafa, Badr Eldin; Omrani, Mohammádreza; Abdelmotal, Abdelfatah; Moukarzel, Nabil

2012-01-01

Chronic respiratory diseases such as asthma and allergic rhinitis (AR) are a major public health problem in developing countries including those in the Middle East. However, to date, there is a paucity of information related to physician-diagnosed AR in this region. The Allergies in Middle East Survey was undertaken to help clarify and broaden the understanding of physician-diagnosed AR across Egypt, Iran, Lebanon, Saudi Arabia, and the United Arab Emirates. The survey explores the frequency of physician-diagnosed AR, prevalence and types of associated symptoms, the impact on quality of life (QOL), current treatment practices, and therapy expectations. In total, 7411 households in five countries (Egypt, Lebanon, Saudi Arabia, Iran and the United Arab Emirates) were screened to identify individuals that were ≥4 years old with a physician diagnosis of AR and either symptoms and/or treatment in the past 12 months. A total of 501 respondents from the five countries completed the survey. Standardized questionnaires were used to make comparisons across the regions; however, the data collection procedures were tailored for each country. The sample was probability based to ensure valid statistical inference to the population. Ten percent of the Middle East population surveyed had a physician diagnosis of AR, with 65% of respondents stating that their allergies were intermittent in nature. An otolaryngologist or allergist diagnosed the majority of the individuals surveyed. Runny nose, nasal and throat itching, postnasal drip, and nasal congestion or stuffed up nose were the most common and bothersome symptoms of AR. The majority of survey participants (58% of the overall survey population) with AR reported that the condition had an impact on their daily private and professional life. Seventy-two percent of adults reported that their AR symptoms limited their work/school activities and 35% reported that their AR interfered with and caused them to miss work or school within the past 12 months. One factor, in addition to the outward AR symptoms, that could have contributed to these function impairments may have been sleep disturbances. Although a secondary symptom to AR, sleep disturbances (difficulty getting to sleep, waking up during the night or lack of a good night's sleep) were shown in this survey to be extremely troubling in ∼15% of AR sufferers. In the past year >90% of patients reported taking a medication of any type for their AR, with nearly a 4:1 ratio of patients taking a prescription medication versus an over-the-counter (OTC) medication in the past 4 weeks. Over 75% of survey respondents reported taking an intranasal corticosteroid (INCS) in the last 4 weeks and the satisfaction rate of INCS medications was similar to that reported for OTC medications. The most common reasons cited for dissatisfaction with INCS medications were inadequate effectiveness, bothersome side effects (e.g., unpleasant taste and retrograde drainage into the pharynx), decreased effectiveness with chronic use, and failure to provide 24-hour relief. These data show that AR is common in the Middle East region as elsewhere in the world. Many patients with AR in Middle East region suffer from their symptoms (e.g., runny nose, nasal itching, nasal congestion, postnasal drip, and other symptoms) on all or most days during the times of the year that their allergies are worst. These symptoms have been shown to reduce QOL and performance at work/school to a significant degree. Additionally, the survey data underscore a considerable treatment gap with current therapies for AR and that many AR patients still have not found adequate effectiveness with currently available medications. Thus, through identification of disease impact on the Middle East population and highlighting treatment gaps, clinicians in the Middle East may better understand and treat AR, leading to improvements in overall patient satisfaction and QOL.

Nasal allergies in the Middle Eastern population: Results from the "Allergies in Middle East Survey".

PubMed

Abdulrahman, Hussain; Hadi, Usamah; Tarraf, Hisham; Gharagozlou, Mohammad; Kamel, Mohamed; Soliman, Alaa; Hamad, Walid Abou; Hanna, Kamal Maurice; Mostafa, Badr Eldin; Omrani, Mohammádreza; Abdelmotal, Abdelfatah; Moukarzel, Nabil

2012-11-01

Chronic respiratory diseases such as asthma and allergic rhinitis (AR) are a major public health problem in developing countries including those in the Middle East. However, to date, there is a paucity of information related to physician-diagnosed AR in this region. The Allergies in Middle East Survey was undertaken to help clarify and broaden the understanding of physician-diagnosed AR across Egypt, Iran, Lebanon, Saudi Arabia, and the United Arab Emirates. The survey explores the frequency of physician-diagnosed AR, prevalence and types of associated symptoms, the impact on quality of life (QOL), current treatment practices, and therapy expectations. In total, 7411 households in five countries (Egypt, Lebanon, Saudi Arabia, Iran and the United Arab Emirates) were screened to identify individuals that were ≥4 years old with a physician diagnosis of AR and either symptoms and/or treatment in the past 12 months. A total of 501 respondents from the five countries completed the survey. Standardized questionnaires were used to make comparisons across the regions; however, the data collection procedures were tailored for each country. The sample was probability based to ensure valid statistical inference to the population. Ten percent of the Middle East population surveyed had a physician diagnosis of AR, with 65% of respondents stating that their allergies were intermittent in nature. An otolaryngologist or allergist diagnosed the majority of the individuals surveyed. Runny nose, nasal and throat itching, postnasal drip, and nasal congestion or stuffed up nose were the most common and bothersome symptoms of AR. The majority of survey participants (58% of the overall survey population) with AR reported that the condition had an impact on their daily private and professional life. Seventy-two percent of adults reported that their AR symptoms limited their work/school activities and 35% reported that their AR interfered with and caused them to miss work or school within the past 12 months. One factor, in addition to the outward AR symptoms, that could have contributed to these function impairments may have been sleep disturbances. Although a secondary symptom to AR, sleep disturbances (difficulty getting to sleep, waking up during the night or lack of a good night's sleep) were shown in this survey to be extremely troubling in ∼15% of AR sufferers. In the past year >90% of patients reported taking a medication of any type for their AR, with nearly a 4:1 ratio of patients taking a prescription medication versus an over-the-counter (OTC) medication in the past 4 weeks. Over 75% of survey respondents reported taking an intranasal corticosteroid (INCS) in the last 4 weeks and the satisfaction rate of INCS medications was similar to that reported for OTC medications. The most common reasons cited for dissatisfaction with INCS medications were inadequate effectiveness, bothersome side effects (e.g., unpleasant taste and retrograde drainage into the pharynx), decreased effectiveness with chronic use, and failure to provide 24-hour relief. These data show that AR is common in the Middle East region as elsewhere in the world. Many patients with AR in Middle East region suffer from their symptoms (e.g., runny nose, nasal itching, nasal congestion, postnasal drip, and other symptoms) on all or most days during the times of the year that their allergies are worst. These symptoms have been shown to reduce QOL and performance at work/school to a significant degree. Additionally, the survey data underscore a considerable treatment gap with current therapies for AR and that many AR patients still have not found adequate effectiveness with currently available medications. Thus, through identification of disease impact on the Middle East population and highlighting treatment gaps, clinicians in the Middle East may better understand and treat AR, leading to improvements in overall patient satisfaction and QOL.

INTERPRETING ERUPTIVE BEHAVIOR IN NOAA AR 11158 VIA THE REGION'S MAGNETIC ENERGY AND RELATIVE-HELICITY BUDGETS

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

Tziotziou, Kostas; Georgoulis, Manolis K.; Liu Yang

In previous works, we introduced a nonlinear force-free method that self-consistently calculates the instantaneous budgets of free magnetic energy and relative magnetic helicity in solar active regions (ARs). Calculation is expedient and practical, using only a single vector magnetogram per computation. We apply this method to a time series of 600 high-cadence vector magnetograms of the eruptive NOAA AR 11158 acquired by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory over a five-day observing interval. Besides testing our method extensively, we use it to interpret the dynamical evolution in the AR, including eruptions. We find that themore » AR builds large budgets of both free magnetic energy and relative magnetic helicity, sufficient to power many more eruptions than the ones it gave within the interval of interest. For each of these major eruptions, we find eruption-related decreases and subsequent free-energy and helicity budgets that are consistent with the observed eruption (flare and coronal mass ejection (CME)) sizes. In addition, we find that (1) evolution in the AR is consistent with the recently proposed (free) energy-(relative) helicity diagram of solar ARs, (2) eruption-related decreases occur before the flare and the projected CME-launch times, suggesting that CME progenitors precede flares, and (3) self terms of free energy and relative helicity most likely originate from respective mutual terms, following a progressive mutual-to-self conversion pattern that most likely stems from magnetic reconnection. This results in the non-ideal formation of increasingly helical pre-eruption structures and instigates further research on the triggering of solar eruptions with magnetic helicity firmly placed in the eruption cadre.« less

Fear Conditioning Selectively Disrupts Noradrenergic Facilitation of GABAergic Inhibition in the Basolateral Amygdala

PubMed Central

Skelly, M. J.; Ariwodola, O. J.; Weiner, J. L.

2016-01-01

Inappropriate fear memory formation is symptomatic of many psychopathologies, and delineating the neurobiology of non-pathological fear learning may provide critical insight into treating these disorders. Fear memory formation is associated with decreased inhibitory signaling in the basolateral amygdala (BLA), and disrupted noradrenergic signaling may contribute to this decrease. BLA noradrenergic neurotransmission has been implicated in fear memory formation, and distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory neurotransmission in this region. For example, α1-ARs promote GABA release from local inhibitory interneurons, while β3-ARs potentiate neurotransmission at lateral paracapsular (LPC) GABAergic synapses. Conversely, β1/2-ARs amplify excitatory signaling at glutamatergic synapses in the BLA. As increased BLA excitability promotes fear memory formation, we hypothesized that fear learning shifts the balanced regional effects of noradrenergic signaling toward excitation. To test this hypothesis, we used the fear-potentiated startle paradigm in combination with whole cell patch clamp electrophysiology to examine the effects of AR activation on BLA synaptic transmission following fear conditioning in male Long-Evans rats. We first demonstrated that inhibitory neurotransmission is decreased at both local and LPC synapses following fear conditioning. We next measured noradrenergic facilitation of BLA inhibitory signaling at local and LPC synapses using α1- and β3-AR agonists (1μM A61603 and 10μM BRL37344), and found that the ability of these agents to facilitate inhibitory neurotransmission is disrupted following fear conditioning. Conversely, we found that fear learning does not disrupt noradrenergic modulation of glutamatergic signaling via a β1/2-AR agonist (1μM isoproterenol). Taken together, these studies suggest that fear learning increases BLA excitability by selectively disrupting the inhibitory effects of noradrenaline. PMID:27720769

Fear conditioning selectively disrupts noradrenergic facilitation of GABAergic inhibition in the basolateral amygdala.

PubMed

Skelly, M J; Ariwodola, O J; Weiner, J L

2017-02-01

Inappropriate fear memory formation is symptomatic of many psychopathologies, and delineating the neurobiology of non-pathological fear learning may provide critical insight into treating these disorders. Fear memory formation is associated with decreased inhibitory signaling in the basolateral amygdala (BLA), and disrupted noradrenergic signaling may contribute to this decrease. BLA noradrenergic neurotransmission has been implicated in fear memory formation, and distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory neurotransmission in this region. For example, α1-ARs promote GABA release from local inhibitory interneurons, while β3-ARs potentiate neurotransmission at lateral paracapsular (LPC) GABAergic synapses. Conversely, β1/2-ARs amplify excitatory signaling at glutamatergic synapses in the BLA. As increased BLA excitability promotes fear memory formation, we hypothesized that fear learning shifts the balanced regional effects of noradrenergic signaling toward excitation. To test this hypothesis, we used the fear-potentiated startle paradigm in combination with whole cell patch clamp electrophysiology to examine the effects of AR activation on BLA synaptic transmission following fear conditioning in male Long-Evans rats. We first demonstrated that inhibitory neurotransmission is decreased at both local and LPC synapses following fear conditioning. We next measured noradrenergic facilitation of BLA inhibitory signaling at local and LPC synapses using α1-and β3-AR agonists (1 μM A61603 and 10 μM BRL37344), and found that the ability of these agents to facilitate inhibitory neurotransmission is disrupted following fear conditioning. Conversely, we found that fear learning does not disrupt noradrenergic modulation of glutamatergic signaling via a β1/2-AR agonist (1 μM isoproterenol). Taken together, these studies suggest that fear learning increases BLA excitability by selectively disrupting the inhibitory effects of noradrenaline. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development.

PubMed

Ittiwut, Chupong; Pratuangdejkul, Jaturong; Supornsilchai, Vichit; Muensri, Sasipa; Hiranras, Yodporn; Sahakitrungruang, Taninee; Watcharasindhu, Suttipong; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2017-01-01

Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD. A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of the SRD5A2 and AR genes was performed. Molecular modeling analysis of the androgen receptor-ligand-binding domain (AR-LBD) of a novel mutation was constructed. Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations in SRD5A2 and AR, respectively. Two novel mutations, SRD5A2 c.383A>G (p.Y128C) and AR c.2176C>T (p.R726C), were identified. Dimensional structural analysis of the novel mutated AR (p.R726C) revealed that it affected the co-activator binding [binding function-3 (BF-3)], not the testosterone binding site. Short phallus length was associated with 5α-reductase deficiency. Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of SRD5A2 and AR were identified. The novel mutated AR (p.R726C) might affect the co-activator binding (BF-3), not the testosterone binding site.

Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players.

PubMed

Warden, S J; Weatherholt, A M; Gudeman, A S; Mitchell, D C; Thompson, W R; Fuchs, R K

2017-07-01

Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (<-2, -2 to 2, 2 to 4, 4 to 10, and >10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSI P ) were assessed. Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSI P resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p < 0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p < 0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSI P (p < 0.001). These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.

HINODE/EIS SPECTROSCOPIC VALIDATION OF VERY HOT PLASMA IMAGED WITH THE SOLAR DYNAMICS OBSERVATORY IN NON-FLARING ACTIVE REGION CORES

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

Testa, Paola; Reale, Fabio, E-mail: ptesta@cfa.harvard.edu

2012-05-01

We use coronal imaging observations with the Solar Dynamics Observatory/Atmospheric Imaging Assembly (AIA), and Hinode/Extreme-ultraviolet Imaging Spectrometer (EIS) spectral data to explore the potential of narrowband EUV imaging data for diagnosing the presence of hot (T {approx}> 5 MK) coronal plasma in active regions. We analyze observations of two active regions (AR 11281, AR 11289) with simultaneous AIA imaging and EIS spectral data, including the Ca XVII line (at 192.8 A), which is one of the few lines in the EIS spectral bands sensitive to hot coronal plasma even outside flares. After careful co-alignment of the imaging and spectral data,more » we compare the morphology in a three-color image combining the 171, 335, and 94 A AIA spectral bands, with the image obtained for Ca XVII emission from the analysis of EIS spectra. We find that in the selected active regions the Ca XVII emission is strong only in very limited areas, showing striking similarities with the features bright in the 94 A (and 335 A) AIA channels and weak in the 171 A band. We conclude that AIA imaging observations of the solar corona can be used to track hot plasma (6-8 MK), and so to study its spatial variability and temporal evolution at high spatial and temporal resolution.« less

BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression

DTIC Science & Technology

2007-12-01

mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to play a...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task...the above construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

PubMed

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

2016-01-06

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

PubMed Central

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

2016-01-01

ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. PMID:26739052

Speed of CMEs and the Magnetic Non-Potentiality of Their Source ARs

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Falconer, David A.; Moore, Ronald L.; Venkatakrishnan, P.

2014-01-01

Most fast coronal mass ejections (CMEs) originate from solar active regions (ARs). Non-potentiality of ARs is expected to determine the speed and size of CMEs in the outer corona. Several other unexplored parameters might be important as well. To find out the correlation between the initial speed of CMEs and the non-potentiality of source ARs, we associated over a hundred of CMEs with source ARs via their co-produced flares. The speed of the CMEs are collected from the SOHO LASCO CME catalog. We have used vector magnetograms obtained mainly with HMI/SDO, also with Hinode (SOT/SP) when available within an hour of a CME occurrence, to evaluate various magnetic non-potentiality parameters, e.g. magnetic free-energy proxies, computed magnetic free energy, twist, shear angle, signed shear angle etc. We have also included several other parameters e.g. total unsigned flux, net current, magnetic area of ARs, area of sunspots, to investigate their correlation, if any, with the initial speeds of CMEs. Our preliminary results show that the ARs with larger non-potentiality and area mostly produce fast CMEs but they can also produce slower ones. The ARs with lesser non-potentiality and area generally produce only slower CMEs, however, there are a few exceptions. The total unsigned flux correlate with the non-potentiality parameters and area of ARs but some ARs with large unsigned flux are also found to be least non-potential. A more detailed analysis is underway.

ACTIVE REGION FILAMENTS MIGHT HARBOR WEAK MAGNETIC FIELDS

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

Díaz Baso, C. J.; Martínez González, M. J.; Asensio Ramos, A., E-mail: cdiazbas@iac.es

Recent spectropolarimetric observations of active region filaments have revealed polarization profiles with signatures typical of the strong field Zeeman regime. The conspicuous absence in those observations of scattering polarization and Hanle effect signatures was then pointed out by some authors. This was interpreted as either a signature of mixed “turbulent” field components or as a result of optical thickness. In this article, we present a natural scenario to explain these Zeeman-only spectropolarimetric observations of active region (AR) filaments. We propose a two-component model, one on top of the other. Both components have horizontal fields, with the azimuth difference between themmore » being close to 90°. The component that lies lower in the atmosphere is permeated by a strong field of the order of 600 G, while the upper component has much weaker fields, of the order of 10 G. The ensuing scattering polarization signatures of the individual components have opposite signs, so its combination along the line of sight reduces—and even can cancel out—the Hanle signatures, giving rise to an apparent Zeeman-only profile. This model is also applicable to other chromospheric structures seen in absorption above ARs.« less

IAU South West Asian ROAD

NASA Astrophysics Data System (ADS)

Mickaelian, Areg; Azatyan, Naira; Farmanyan, Sona; Mikayelyan, Gor

2016-10-01

Armenia is hosting the IAU South West Asian (SWA) Regional Office of Astronomy for Development (ROAD). It is a county of ancient astronomy and is also rich in modern astronomical facilities and infrastructures, hence may successfully serve as a regional center for various activities. Byurakan Astrophysical Observatory (BAO) has 2.6m and 1m Schmidt, as well as a number of smaller telescopes that are an observational basis for joint projects and collaborations. Armenian Virtual Observatory (ArVO) is hosting astronomical databases, such as the Digitized First Byurakan Survey (DFBS) and may also serve as a basis for development of VO structures in this region. Recently we have conducted a number of new activities; a meeting on ``Relation of Astronomy to other Sciences, Culture and Society" (RASCS) was organized by BAO and Armenian Astronomical Society (ArAS) in Oct 2014 in Byurakan. Activities related to Archaeoastronomy and Astronomy in Culture (AAC) were initiated as well. Discussions on future Armenian-Iranian collaboration in astronomy were carried out, including an Armenian-Iranian Astronomical Workshop held in Oct 2015 in Byurakan. Similar workshops have been carried out between BAO and Abastumani Astronomical Observatory (AbAO, Georgia) since 1974.

A gigantic coronal jet ejected from a compact active region in a coronal hole

NASA Technical Reports Server (NTRS)

Shibata, K.; Nitta, N.; Strong, K. T.; Matsumoto, R.; Yokoyama, T.; Hirayama, T.; Hudson, H.; Ogawara, Y.

1994-01-01

A gigantic coronal jet greater than 3 x 10(exp 5) km long (nearly half the solar radius) has been found with the soft X-ray telescope (SXT) on board the solar X-ray satellite, Yohkoh. The jet was ejected on 1992 January 11 from an 'anemone-type' active region (AR) appearing in a coronal hole and is one of the largest coronal X-ray jets observed so far by SXT. This gigantic jet is the best observed example of many other smaller X-ray jets, because the spatial structures of both the jet and the AR located at its base are more easily resolved. The range of apparent translational velocities of the bulk of the jet was between 90 and 240 km s(exp -1), with the corresponding kinetic energy estimated to be of order of 10(exp 28) ergs. A detailed analysis reveals that the jet was associated with a loop brightening (a small flare) that occurred in the active region. Several features of this observation suggest and are consistent with a magnetic reconnection mechanism for the production of such a 'jet-loop-brightening' event.

Triggering Process of the X1.0 Three-ribbon Flare in the Great Active Region NOAA 12192

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

Bamba, Yumi; Inoue, Satoshi; Kusano, Kanya

The solar magnetic field in a flare-producing active region (AR) is much more complicated than theoretical models, which assume a very simple magnetic field structure. The X1.0 flare, which occurred in AR 12192 on 2014 October 25, showed a complicated three-ribbon structure. To clarify the trigger process of the flare and to evaluate the applicability of a simple theoretical model, we analyzed the data from Hinode /Solar Optical Telescope and the Solar Dynamics Observatory /Helioseismic and Magnetic Imager, Atmospheric Imaging Assembly. We investigated the spatio-temporal correlation between the magnetic field structures, especially the non-potentiality of the horizontal field, and themore » bright structures in the solar atmosphere. As a result, we determined that the western side of the positive polarity, which is intruding on a negative polarity region, is the location where the flare was triggered. This is due to the fact that the sign of the magnetic shear in that region was opposite that of the major shear of the AR, and the significant brightenings were observed over the polarity inversion line (PIL) in that region before flare onset. These features are consistent with the recently proposed flare-trigger model that suggests that small reversed shear (RS) magnetic disturbances can trigger solar flares. Moreover, we found that the RS field was located slightly off the flaring PIL, contrary to the theoretical prediction. We discuss the possibility of an extension of the RS model based on an extra numerical simulation. Our result suggests that the RS field has a certain flexibility for displacement from a highly sheared PIL, and that the RS field triggers more flares than we expected.« less

Block-induced Complex Structures Building the Flare-productive Solar Active Region 12673

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

Yang, Shuhong; Zhang, Jun; Zhu, Xiaoshuai

Solar active region (AR) 12673 produced 4 X-class, 27 M-class, and numerous lower-class flares during its passage across the visible solar disk in 2017 September. Our study is to answer the questions why this AR was so flare-productive and how the X9.3 flare, the largest one of the past decade, took place. We find that there was a sunspot in the initial several days, and then two bipolar regions emerged nearby it successively. Due to the standing of the pre-existing sunspot, the movement of the bipoles was blocked, while the pre-existing sunspot maintained its quasi-circular shaped umbra only with themore » disappearance of a part of penumbra. Thus, the bipolar patches were significantly distorted, and the opposite polarities formed two semi-circular shaped structures. After that, two sequences of new bipolar regions emerged within the narrow semi-circular zone, and the bipolar patches separated along the curved channel. The new bipoles sheared and interacted with the previous ones, forming a complex topological system, during which numerous flares occurred. At the highly sheared region, a great deal of free energy was accumulated. On September 6, one negative patch near the polarity inversion line began to rapidly rotate and shear with the surrounding positive fields, and consequently the X9.3 flare erupted. Our results reveal that the block-induced complex structures built the flare-productive AR and the X9.3 flare was triggered by an erupting filament due to the kink instability. To better illustrate this process, a block-induced eruption model is proposed for the first time.« less

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.

Development of a Low-Level Ar-37 Calibration Standard

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

Williams, Richard M.; Aalseth, Craig E.; Bowyer, Ted W.

Argon-37 is an important environmental signature of an underground nuclear explosion. Producing and quantifying low-level 37Ar standards is an important step in the development of sensitive field measurement instruments for use during an On-Site Inspection, a key provision of the Comprehensive Nuclear-Test-Ban Treaty. This paper describes progress at Pacific Northwest National Laboratory (PNNL) in the development of a process to generate and quantify low-level 37Ar standard material, which can then be used to calibrate sensitive field systems at activities consistent with soil background levels. The 37Ar used for our work was generated using a laboratory-scale, high-energy neutron source to irradiatemore » powdered samples of calcium carbonate. Small aliquots of 37Ar were then extracted from the head space of the irradiated samples. The specific activity of the head space samples, mixed with P10 (90% stable argon:10% methane by mole fraction) count gas, is then derived using the accepted Length-Compensated Internal-Source Proportional Counting method. Due to the low activity of the samples, a set of three Ultra-Low Background Proportional-Counters designed and fabricated at PNNL from radio-pure electroformed copper was used to make the measurements in PNNL’s shallow underground counting laboratory. Very low background levels (<10 counts/day) have been observed in the spectral region near the 37Ar emission feature at 2.8 keV. Two separate samples from the same irradiation were measured. The first sample was counted for 12 days beginning 28 days after irradiation, the second sample was counted for 24 days beginning 70 days after irradiation (the half-life of 37Ar is 35.0 days). Both sets of measurements were analyzed and yielded very similar results for the starting activity (~0.1 Bq) and activity concentration (0.15 mBq/ccSTP argon) after P10 count gas was added. A detailed uncertainty model was developed based on the ISO Guide to the Expression of Uncertainty in Measurement. This paper presents a discussion of the measurement analysis, along with assumptions and uncertainty estimates.« less

A statistical study on synergetic effects of atmospheric rivers and cut-off lows upon precipitation

NASA Astrophysics Data System (ADS)

Tsuji, H.; Takayabu, Y. N.

2017-12-01

Effects of atmospheric rivers (ARs) on precipitation in the western North Pacific (WNP) region has been less studied compared with that in the eastern Pacific. Recently, Hirota et al. (2016, MWR) analyzed the extreme rainfall event which caused a disastrous flood in Hiroshima, Japan, on 19 August 2014. They showed that a coincidence of very moist troposphere associated with AR and instability and dynamical ascent associated with a cut-off low (COL) played a significant role for the rainfall event. As in this case, AR in the WNP region seems to enhance rainfall with additional instability or ascending motion brought by another system. However, it is not clear how far large-scale conditions such as AR and COL can determine locations of severe rainfall. In this study, we statistically investigate the differences in precipitation between cases in which AR exists near a COL (AR category) and those in which AR does not exist near a COL (non-AR category). Precipitation data are obtained from hourly Global Satellite Mapping of Precipitation (GSMaP) data (0.1 degree grid). We define AR and COL with six-hourly JRA55 (1.25 degree grid) precipitable water (PW) and 350 K isentropic potential vorticity, respectively. The analyses are conducted in the WNP region (100E-160W, 0-60N), from March 2000 to February 2013. Composite results show that precipitation amount around the front side of COL's moving direction (north) in the AR category (139 cases) is larger than that in the non-AR category (63 cases). In particular, the difference of precipitation around the front-left side (north-west) is statistically significant. The relationship among the locations of COL, positive PW anomaly region corresponding to AR, and the region where the difference of precipitation is statistically significant is similar with that among the locations of COL, AR, and extreme precipitation area in the event of Hiroshima. It is indicated that a precipitation enhancement can occur associated with a synergistic effect of large-scale conditions such as AR and a COL, and Hiroshima flood was one of such cases. Acknowledgments: This research was supported by the Environment Research and Technology Development Fund (2-1503) of Environmental Restoration and Conservation Agency, and JSPS KAKENHI Grant Number 15H02132.

The Impacts of Atmospheric Rivers on California's Extreme Precipitation

NASA Astrophysics Data System (ADS)

Asgari Lamjiri, M.; Dettinger, M. D.; Ralph, M.

2017-12-01

Atmospheric rivers (ARs) are long, narrow corridors of enhanced water vapor transport that are typically associated with extratropical cyclones. ARs can be beneficial and replenish water resources, be hazardous and cause damaging floods, or have a combination of hazardous and beneficial impacts. Thus, understanding hydrologic impacts of ARs can help to improve water reservoir management and enhance flood risk mitigation, especially in California where there is extremely large year-to-year variability in annual precipitation accumulations. At the continental scale, gridded hourly precipitation observations are used in this study to identify unique characteristics of precipitation events impacting the US west coast compared to other regions in the US; precipitation events are defined here as continuous periods of precipitation with at least 5 mm of accumulated precipitation. It is shown that on average, the US west coast receives the largest precipitation totals across the US; these extreme precipitation events are largely associated with the most persistent ARs. Within California, hourly precipitation observations from 200 sites are being analyzed to better understand distinct categories of ARs that dictate extreme precipitation in different regions of California. It is found that, on average, the north coast, northern Sierra, and the Transverse Ranges experience the largest precipitation events; north coast and northern Sierra precipitation events tend to be longer, whereas the Transverse Ranges generally experience higher maximum and event-averaged intensities. ARs contribute significantly to extreme precipitation events in all regions of California, particularly the north coast, northern Sierra, and the Transverse Ranges. ARs associated with extreme precipitation events across California are significantly more persistent and have higher integrated vapor transport intensities than those associated with non-extreme events. Composites of characteristics of ARs which yield extreme precipitation events in different regions of California are studied to categorize the most impactful ARs in each region.

Comparison of functional network connectivity for passive-listening and active-response narrative comprehension in adolescents.

PubMed

Wang, Yingying; Holland, Scott K

2014-05-01

Comprehension of narrative stories plays an important role in the development of language skills. In this study, we compared brain activity elicited by a passive-listening version and an active-response (AR) version of a narrative comprehension task by using independent component (IC) analysis on functional magnetic resonance imaging data from 21 adolescents (ages 14-18 years). Furthermore, we explored differences in functional network connectivity engaged by two versions of the task and investigated the relationship between the online response time and the strength of connectivity between each pair of ICs. Despite similar brain region involvements in auditory, temporoparietal, and frontoparietal language networks for both versions, the AR version engages some additional network elements including the left dorsolateral prefrontal, anterior cingulate, and sensorimotor networks. These additional involvements are likely associated with working memory and maintenance of attention, which can be attributed to the differences in cognitive strategic aspects of the two versions. We found significant positive correlation between the online response time and the strength of connectivity between an IC in left inferior frontal region and an IC in sensorimotor region. An explanation for this finding is that longer reaction time indicates stronger connection between the frontal and sensorimotor networks caused by increased activation in adolescents who require more effort to complete the task.

Seasonal precipitation patterns along pathways of South American low-level jets and aerial rivers

NASA Astrophysics Data System (ADS)

Poveda, Germán.; Jaramillo, Liliana; Vallejo, Luisa F.

2014-01-01

We study the seasonal dynamics of the eastern Pacific (CHOCO) and Caribbean low-level jets (LLJ), and aerial rivers (AR) acting on tropical and subtropical South America. Using the ERA-Interim reanalysis (1979-2012), we show that the convergence of both LLJs over the eastern Pacific-western Colombia contributes to the explanation of the region's world-record rainfall. Diverse variables involved in the transport and storage of moisture permit the identification of an AR over northern South America involving a midtropospheric easterly jet that connects the Atlantic and Pacific Oceans across the Andes, with stronger activity in April to August. Other major seasonal AR pathways constitute part of a large gyre originating over the tropical North Atlantic, veering to the southeast over the eastern Andes and reaching regions of northern Argentina and southeastern Brazil. We illustrate the distribution of average seasonal precipitation along the LLJs and AR pathways with data from the Tropical Rainfall Measuring Mission (1998-2011), combined with considerations of CAPE, topography, and land cover. In addition, the theory of the biotic pump of atmospheric moisture (BiPAM) is tested at seasonal time scales, and found to hold in 8 out of 12 ARs, and 22 out of 32 forest-covered tracks (64% in distance) along the ARs. Deviations from BiPAM's predictions of rainfall distribution are explained by the effects of topography, orography, and land cover types different from forests. Our results lend a strong observational support to the BiPAM theory at seasonal time scales over South American forested flat lands.

The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT(1A) and 5-HT(2A) receptors.

PubMed

Riga, Maurizio S; Bortolozzi, Analia; Campa, Letizia; Artigas, Francesc; Celada, Pau

2016-02-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT(1A)/5-HT(2A)-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT(1A)-R and 5-HT(2A)-R, using wild type (WT) and 5-HT(2A)-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT(1A)-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT(1A)-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT(1A)-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT(1A)-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT(2A)-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of Ascochyta rabiei for population structure, mating type and pathogenic variability from Pakistan and United States

USDA-ARS?s Scientific Manuscript database

Chickpea production is greatly hampered by blight causing fungal pathogen Ascochyta rabiei (AR) in chickpea growing regions of the world. Genetic variability and mating type frequency of thirty-two AR isolates from six geographical regions of Pakistan were compared with a US-AR population. Pakistani...

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

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.

ON POLAR MAGNETIC FIELD REVERSAL AND SURFACE FLUX TRANSPORT DURING SOLAR CYCLE 24

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

Sun, Xudong; Todd Hoeksema, J.; Liu, Yang

As each solar cycle progresses, remnant magnetic flux from active regions (ARs) migrates poleward to cancel the old-cycle polar field. We describe this polarity reversal process during Cycle 24 using four years (2010.33-2014.33) of line-of-sight magnetic field measurements from the Helioseismic and Magnetic Imager. The total flux associated with ARs reached maximum in the north in 2011, more than two years earlier than the south; the maximum is significantly weaker than Cycle 23. The process of polar field reversal is relatively slow, north-south asymmetric, and episodic. We estimate that the global axial dipole changed sign in 2013 October; the northernmore » and southern polar fields (mean above 60° latitude) reversed in 2012 November and 2014 March, respectively, about 16 months apart. Notably, the poleward surges of flux in each hemisphere alternated in polarity, giving rise to multiple reversals in the north. We show that the surges of the trailing sunspot polarity tend to correspond to normal mean AR tilt, higher total AR flux, or slower mid-latitude near-surface meridional flow, while exceptions occur during low magnetic activity. In particular, the AR flux and the mid-latitude poleward flow speed exhibit a clear anti-correlation. We discuss how these features can be explained in a surface flux transport process that includes a field-dependent converging flow toward the ARs, a characteristic that may contribute to solar cycle variability.« less

Uncovering the role of the East Asian jet stream and heterogeneities in atmospheric rivers affecting the western United States.

PubMed

Zhang, Wei; Villarini, Gabriele

2018-01-30

Atmospheric rivers (ARs) exert major socioeconomic repercussions along the US West Coast by inducing heavy rainfall, flooding, strong winds, and storm surge. Despite the significant societal and economic repercussions of these storms, our understanding of the physical drivers responsible for their interannual variability is limited, with different climate modes identified as possible mechanisms. Here we show that the Pacific-Japan (PJ) teleconnections/patterns and the East Asian subtropical jet (EASJ) exhibit a strong linkage with the total frequency of ARs making landfall over the western United States, much stronger than the other potential climate modes previously considered. While our findings indicate that the PJ pattern and EASJ are the most relevant climate modes driving the overall AR activity, we also uncover heterogeneities in AR tracks. Specifically, we show that not all ARs making landfall along the West Coast come from a single population, but rather that it is possible to stratify these storms into three clusters. While the PJ pattern and EASJ are major drivers of AR activity for two clusters, the cluster that primarily affects the US Southwest is largely driven by other climate modes [El Niño Southern Oscillation (ENSO), the Atlantic meridional mode (AMM), the Pacific-North America (PNA) teleconnection pattern, and the North Pacific Gyre Oscillation (NPGO)]. Therefore, important regional differences exist and this information can substantially enhance our ability to predict and prepare for these storms and their impacts.

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.

Ars insulator identified in sea urchin possesses an activity to ensure the transgene expression in mouse cells.

PubMed

Tajima, Shoji; Shinohara, Keiko; Fukumoto, Maiko; Zaitsu, Reiko; Miyagawa, Junichi; Hino, Shinjiro; Fan, Jun; Akasaka, Koji; Matsuoka, Masao

2006-04-01

Sea urchin arylsulfatase (Ars) gene locus has features of an insulator, i.e., blocking of enhancer and promoter interaction, and protection of a transgene against positional effects [Akasaka et al. (1999) Cell. Mol. Biol. 45, 555-565]. To examine the effect of Ars insulator on long-term expression of a transgene, the insulator was inserted into LTR of retrovirus vector harboring hrGFP gene as a reporter, and then introduced into mouse myoblast cells. The isolated clones transduced with the reporter gene with or without Ars insulator were cultured for more than 20 wk in the absence of a selection reagent, and the expression of hrGFP was periodically determined. Expression of hrGFP in four clones transduced with the reporter gene without Ars insulator was completely silenced after 20 wk of culture. On the other hand, hrGFP was expressed in all clones with Ars insulator inserted in one of the two different orientations. Histone H3 deacetylation and DNA methylation of the 5'LTR promoter region, signs for heterochromatin and silencing, were suppressed in the clones that were expressing hrGFP. Ars insulator is effective in maintaining a transgene in mouse cells in an orientation-dependent manner, and will be a useful tool to ensure stable expression of a transgene.

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...

Diffusion-Driven Charge Transport in Light Emitting Devices

PubMed Central

Oksanen, Jani; Suihkonen, Sami

2017-01-01

Almost all modern inorganic light-emitting diode (LED) designs are based on double heterojunctions (DHJs) whose structure and current injection principle have remained essentially unchanged for decades. Although highly efficient devices based on the DHJ design have been developed and commercialized for energy-efficient general lighting, the conventional DHJ design requires burying the active region (AR) inside a pn-junction. This has hindered the development of emitters utilizing nanostructured ARs located close to device surfaces such as nanowires or surface quantum wells. Modern DHJ III-N LEDs also exhibit resistive losses that arise from the DHJ device geometry. The recently introduced diffusion-driven charge transport (DDCT) emitter design offers a novel way to transport charge carriers to unconventionally placed ARs. In a DDCT device, the AR is located apart from the pn-junction and the charge carriers are injected into the AR by bipolar diffusion. This device design allows the integration of surface ARs to semiconductor LEDs and offers a promising method to reduce resistive losses in high power devices. In this work, we present a review of the recent progress in gallium nitride (GaN) based DDCT devices, and an outlook of potential DDCT has for opto- and microelectronics. PMID:29231900

The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.

PubMed

Correa, Ricardo G; Krajewska, Maryla; Ware, Carl F; Gerlic, Motti; Reed, John C

2014-03-30

Prostate cancer (PCa) is among the leading causes of cancer-related death in men. Androgen receptor (AR) signaling plays a seminal role in prostate development and homeostasis, and dysregulation of this pathway is intimately linked to prostate cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related protein NWD1 as a novel modulator of AR signaling. We determined that expression of NWD1 becomes elevated during prostate cancer progression, based on analysis of primary tumor specimens. Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) family proteins. Gene silencing procedures, in conjunction with transcriptional profiling, showed that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels. Depleting NWD1 in PCa cell lines reduces AR levels and suppresses activity of androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of androgen-dependent LNCaP prostate cancer cells, thus showing its functional importance in an AR-dependent tumor cell model. Proteomic analysis suggested that NWD1 associates with various molecular chaperones commonly related to AR complexes. Altogether, these data suggest a role for tumor-associated over-expression of NWD1 in dysregulation of AR signaling in PCa.

Nicotine Induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

PubMed Central

Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

2011-01-01

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 single 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. PMID:21971485

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

Fast and robust segmentation in the SDO-AIA era

NASA Astrophysics Data System (ADS)

Verbeeck, Cis; Delouille, Véronique; Mampaey, Benjamin; Hochedez, Jean-François; Boyes, David; Barra, Vincent

Solar images from the Atmospheric Imaging Assembly (AIA) aboard the Solar Dynamics Ob-servatory (SDO) will flood the solar physics community with a wealth of information on solar variability, of great importance both in solar physics and in view of Space Weather applica-tions. Obtaining this information, however, requires the ability to automatically process large amounts of data in an objective fashion. In previous work, we have proposed a multi-channel unsupervised spatially-constrained multi-channel fuzzy clustering algorithm (SPoCA) that automatically segments EUV solar images into Active Regions (AR), Coronal Holes (CH), and Quiet Sun (QS). This algorithm will run in near real time on AIA data as part of the SDO Feature Finding Project, a suite of software pipeline modules for automated feature recognition and analysis for the imagery from SDO. After having corrected for the limb brightening effect, SPoCA computes an optimal clustering with respect to the regions of interest using fuzzy logic on a quality criterion to manage the various noises present in the images and the imprecision in the definition of the above regions. Next, the algorithm applies a morphological opening operation, smoothing the cluster edges while preserving their general shape. The process is fast and automatic. A lower size limit is used to distinguish AR from Bright Points. As the algorithm segments the coronal images according to their brightness, it might happen that an AR is detected as several disjoint pieces, if the brightness in between is somewhat lower. Morphological dilation is employed to reconstruct the AR themselves from their constituent pieces. Combining SPoCA's detection of AR, CH, and QS on subsequent images allows automatic tracking and naming of any region of interest. In the SDO software pipeline, SPoCA will auto-matically populate the Heliophysics Events Knowledgebase(HEK) with Active Region events. Further, the algorithm has a huge potential for correct and automatic identification of AR, CH, and QS in any study that aims to address properties of those specific regions in the corona. SPoCA is now ready and waiting to tackle solar cycle 24 using SDO data. While we presently apply SPoCA to EUV data, the method is generic enough to allow the introduction of other channels or data, e.g., Differential Emission Measure (DEM) maps. Because of the unprecedented challenges brought up by the quantity of SDO data, European partners have gathered within an ISSI team on `Mining and Exploiting the NASA Solar Dynam-ics Observatory data in Europe' (a.k.a. Soldyneuro). Its aim is to provide automated feature recognition algorithms for scanning the SDO archive, as well as conducting scientific studies that combine different algorithm's outputs. Within the Soldyneuro project, we will use data from the EUV Variability Experiment (EVE) spectrometer in order to estimate the full Sun DEM. This DEM will next be used to estimate the total flux from AIA images so as to provide a validation for the calibration of AIA.

Multi-spacecraft Observations of the Coronal and Interplanetary Evolution of a Solar Eruption Associated with Two Active Regions

NASA Astrophysics Data System (ADS)

Hu, H.; Liu, Y. D.; Wang, R.; Zhao, X.; Zhu, B.; Yang, Z.

2017-12-01

We investigate the coronal and interplanetary evolution of a coronal mass ejection (CME) launched on 2010 September 4 from a source region linking two active regions (ARs), 11101 and 11103, using extreme ultraviolet imaging, magnetogram, white-light, and in situ observations from SDO, STEREO, SOHO, VEX, and Wind. A potential-field source-surface model is employed to examine the configuration of the coronal magnetic field surrounding the source region. The graduated cylindrical shell model and a triangulation method are applied to determine the kinematics of the CME in the corona and interplanetary space. From the remote sensing and in situ observations, we obtain some key results: (1) the CME was deflected in both the eastward and southward directions in the low corona by the magnetic pressure from the two ARs, and possibly interacted with another ejection, which caused that the CME arrived at VEX that was longitudinally distant from the source region; (2) although VEX was closer to the Sun, the observed and derived CME arrival times at VEX are not earlier than those at Wind, which suggests the importance of determining both the frontal shape and propagation direction of the CME in interplanetary space; and (3) the ICME was compressed in the radial direction while the longitudinal transverse size was extended.

Suppression of Heating of Coronal Loops Rooted in Opposite Polarity Sunspot Umbrae

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep K.; Winebarger, Amy R.

2016-01-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 Å images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-­polarity plage region. The AIA 94 Å images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. The NLFFF model, validated by comparison of calculated model field lines with observed loops in AIA 193 and 94 Å, specifies the photospheric roots of the model field lines. Some model coronal magnetic field lines arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.

Armenia as a Regional Centre for Astronomy for Development activities

NASA Astrophysics Data System (ADS)

Mickaelian, A.

2015-03-01

The Byurakan Astrophysical Observatory (BAO, Armenia, http://www.bao.am) are among the candidate IAU Regional Nodes for Astronomy for Development activities. It is one of the main astronomical centers of the former Soviet Union and the Middle East region. At present there are 48 qualified researchers at BAO, including six Doctors of Science and 30 PhDs. Five important observational instruments are installed at BAO, the larger ones being 2.6m Cassegrain (ZTA-2.6) and 1m Schmidt (the one that provided the famous Markarian survey). BAO is regarded as a national scientific-educational center, where a number of activities are being organized, such as: international conferences (4 IAU symposia and 1 IAU colloquium, JENAM-2007, etc.), small workshops and discussions, international summer schools (1987, 2006, 2008 and 2010), and Olympiads. BAO collaborates with scientists from many countries. The Armenian Astronomical Society (ArAS, http://www.aras.am/) is an NGO founded in 2001; it has 93 members and it is rather active in the organization of educational, amateur, popular, promotional and other matters. The Armenian Virtual Observatory (ArVO, http://www.aras.am/Arvo/arvo.htm) is one of the 17 national VO projects forming the International Virtual Observatories Alliance (IVOA) and is the only VO project in the region serving also for educational purposes. A number of activities are planned, such as management, coordination and evaluation of the IAU programs in the area of development and education, establishment of the new IAU endowed lectureship program and organization of seminars and public lectures, coordination and initiation of fundraising activities for astronomy development, organization of regional scientific symposia, conferences and workshops, support to Galileo Teacher Training Program (GTTP), production/publication of educational and promotional materials, etc.

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

Visualization of arrestin recruitment by a G Protein-Coupled Receptor

PubMed Central

Reis, Rosana I.; Huang, Li-Yin; Tripathi-Shukla, Prachi; Qian, Jiang; Li, Sheng; Blanc, Adi; Oleskie, Austin N.; Dosey, Anne M.; Su, Min; Liang, Cui-Rong; Gu, Ling-Ling; Shan, Jin-Ming; Chen, Xin; Hanna, Rachel; Choi, Minjung; Yao, Xiao Jie; Klink, Bjoern U.; Kahsai, Alem W.; Sidhu, Sachdev S.; Koide, Shohei; Penczek, Pawel A.; Kossiakoff, Anthony A.; Jr, Virgil L. Woods; Kobilka, Brian K.; Skiniotis, Georgios; Lefkowitz, Robert J.

2014-01-01

G Protein Coupled Receptors (GPCRs) are critically regulated by β-arrestins (βarrs), which not only desensitize G protein signaling but also initiate a G protein independent wave of signaling1-5. A recent surge of structural data on a number of GPCRs, including the β2 adrenergic receptor (β2AR)-G protein complex, has provided novel insights into the structural basis of receptor activation6-11. Lacking however has been complementary information on recruitment of βarrs to activated GPCRs primarily due to challenges in obtaining stable receptor-βarr complexes for structural studies. Here, we devised a strategy for forming and purifying a functional β2AR-βarr1 complex that allowed us to visualize its architecture by single particle negative stain electron microscopy (EM) and to characterize the interactions between β2AR and βarr1 using hydrogen-deuterium exchange mass spectrometry (HDXMS) and chemical cross-linking. EM 2D averages and 3D reconstructions reveal bimodal binding of βarr1 to the β2AR, involving two separate sets of interactions, one with the phosphorylated carboxy-terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of cross-linked residues suggest engagement of the finger loop of βarr1 with the seven-transmembrane core of the receptor. In contrast, focal areas of increased HDX indicate regions of increased dynamics in both N and C domains of βarr1 when coupled to the β2AR. A molecular model of the β2AR-βarr signaling complex was made by docking activated βarr1 and β2AR crystal structures into the EM map densities with constraints provided by HDXMS and cross-linking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented herein provides a framework for better understanding the basis of GPCR regulation by arrestins. PMID:25043026

40Ar/39Ar geochronology, paleomagnetism, and evolution of the Boring volcanic field, Oregon and Washington, USA

USGS Publications Warehouse

Fleck, Robert J.; Hagstrum, Jonathan T.; Calvert, Andrew T.; Evarts, Russell C.; Conrey, Richard M.

2014-01-01

The 40Ar/39Ar investigations of a large suite of fine-grained basaltic rocks of the Boring volcanic field (BVF), Oregon and Washington (USA), yielded two primary results. (1) Using age control from paleomagnetic polarity, stratigraphy, and available plateau ages, 40Ar/39Ar recoil model ages are defined that provide reliable age results in the absence of an age plateau, even in cases of significant Ar redistribution. (2) Grouping of eruptive ages either by period of activity or by composition defines a broadly northward progression of BVF volcanism during latest Pliocene and Pleistocene time that reflects rates consistent with regional plate movements. Based on the frequency distribution of measured ages, periods of greatest volcanic activity within the BVF occurred 2.7–2.2 Ma, 1.7–0.5 Ma, and 350–50 ka. Grouped by eruptive episode, geographic distributions of samples define a series of northeast-southwest–trending strips whose centers migrate from south-southeast to north-northwest at an average rate of 9.3 ± 1.6 mm/yr. Volcanic activity in the western part of the BVF migrated more rapidly than that to the east, causing trends of eruptive episodes to progress in an irregular, clockwise sense. The K2O and CaO values of dated samples exhibit well-defined temporal trends, decreasing and increasing, respectively, with age of eruption. Divided into two groups by K2O, the centers of these two distributions define a northward migration rate similar to that determined from eruptive age groups. This age and compositional migration rate of Boring volcanism is similar to the clockwise rotation rate of the Oregon Coast Range with respect to North America, and might reflect localized extension on the trailing edge of that rotating crustal block.

Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

PubMed

Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

2010-04-01

Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens.

PubMed

Stedtfeld, Robert D; Williams, Maggie R; Fakher, Umama; Johnson, Timothy A; Stedtfeld, Tiffany M; Wang, Fang; Khalife, Walid T; Hughes, Mary; Etchebarne, Brett E; Tiedje, James M; Hashsham, Syed A

2016-03-01

An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

40Ar/39Ar dating of the eruptive history of Mount Erebus, Antarctica: Summit flows, tephra, and caldera collapse

USGS Publications Warehouse

Harpel, C.J.; Kyle, P.R.; Esser, R.P.; McIntosh, W.C.; Caldwell, D.A.

2004-01-01

Eruptive activity has occurred in the summit region of Mount Erebus over the last 95 ky, and has included numerous lava flows and small explosive eruptions, at least one plinian eruption, and at least one and probably two caldera-forming events. Furnace and laser step-heating 40Ar/39Ar ages have been determined for 16 summit lava flows and three englacial tephra layers erupted from Mount Erebus. The summit region is composed of at least one or possibly two superimposed calderas that have been filled by post-caldera lava flows ranging in age from 17 ?? 8 to 1 ?? 5 ka. Dated pre-caldera summit flows display two age populations at 95 ?? 9 to 76 ?? 4 ka and 27 ?? 3 to 21 ??4 ka of samples with tephriphonolite and phonolite compositions, respectively. A caldera-collapse event occurred between 25 and 11 ka. An older caldera-collapse event is likely to have occurred between 80 and 24 ka. Two englacial tephra layers from the flanks of Mount Erebus have been dated at 71 ?? 5 and 15 ?? 4 ka. These layers stratigraphically bracket 14 undated tephra layers, and predate 19 undated tephra layers, indicating that small-scale explosive activity has occurred throughout the late Pleistocene and Holocene eruptive history of Mount Erebus. A distal, englacial plinian-fall tephra sample has an age of 39 ?? 6 ka and may have been associated with the older of the two caldera-collapse events. A shift in magma composition from tephriphonolite to phonolite occurred at around 36 ka. ?? Springer-Verlag 2004.

THE NAKED EMERGENCE OF SOLAR ACTIVE REGIONS OBSERVED WITH SDO/HMI

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

Centeno, Rebecca

We take advantage of the HMI/SDO instrument to study the naked emergence of active regions (ARs) from the first imprints of the magnetic field on the solar surface. To this end, we followed the first 24 hr in the life of two rather isolated ARs that appeared on the surface when they were about to cross the central meridian. We analyze the correlations between Doppler velocities and the orientation of the vector magnetic field, consistent finding that the horizontal fields connecting the main polarities are dragged to the surface by relatively strong upflows and are associated with elongated granulation thatmore » is, on average, brighter than its surroundings. The main magnetic footpoints, on the other hand, are dominated by vertical fields and downflowing plasma. The appearance of moving dipolar features (MDFs, of opposite polarity to that of the AR) in between the main footpoints is a rather common occurrence once the AR reaches a certain size. The buoyancy of the fields is insufficient to lift up the magnetic arcade as a whole. Instead, weighted by the plasma that it carries, the field is pinned down to the photosphere at several places in between the main footpoints, giving life to the MDFs and enabling channels of downflowing plasma. MDF poles tend to drift toward each other, merge and disappear. This is likely to be the signature of a reconnection process in the dipped field lines, which relieves some of the weight allowing the magnetic arcade to finally rise beyond the detection layer of the Helioseismic and Magnetic Imager spectral line.« less

Connecting Coronal Mass Ejections to Their Solar Active Region Sources: Combining Results from the HELCATS and FLARECAST Projects

NASA Astrophysics Data System (ADS)

Murray, Sophie A.; Guerra, Jordan A.; Zucca, Pietro; Park, Sung-Hong; Carley, Eoin P.; Gallagher, Peter T.; Vilmer, Nicole; Bothmer, Volker

2018-04-01

Coronal mass ejections (CMEs) and other solar eruptive phenomena can be physically linked by combining data from a multitude of ground-based and space-based instruments alongside models; however, this can be challenging for automated operational systems. The EU Framework Package 7 HELCATS project provides catalogues of CME observations and properties from the Heliospheric Imagers on board the two NASA/STEREO spacecraft in order to track the evolution of CMEs in the inner heliosphere. From the main HICAT catalogue of over 2,000 CME detections, an automated algorithm has been developed to connect the CMEs observed by STEREO to any corresponding solar flares and active-region (AR) sources on the solar surface. CME kinematic properties, such as speed and angular width, are compared with AR magnetic field properties, such as magnetic flux, area, and neutral line characteristics. The resulting LOWCAT catalogue is also compared to the extensive AR property database created by the EU Horizon 2020 FLARECAST project, which provides more complex magnetic field parameters derived from vector magnetograms. Initial statistical analysis has been undertaken on the new data to provide insight into the link between flare and CME events, and characteristics of eruptive ARs. Warning thresholds determined from analysis of the evolution of these parameters is shown to be a useful output for operational space weather purposes. Parameters of particular interest for further analysis include total unsigned flux, vertical current, and current helicity. The automated method developed to create the LOWCAT catalogue may also be useful for future efforts to develop operational CME forecasting.

The SMM UV observations of Active Region 5395

NASA Technical Reports Server (NTRS)

Drake, Stephen A.; Gurman, Joseph B.

1989-01-01

The Ultraviolet Spectrometer and Polarimeter (UVSP) on the Solar Maximum Mission (SMM) spacecraft was used extensively to study the spatial morphology and time variability of solar active regions in the far UV (at approx. wavelength of 1370 A) since July 1985. The normal spatial resolution of UVSP observations in this 2nd-order mode is 10 sec., and the highest temporal resolution is 64 milliseconds. To make a full-field, 4 min. by 4 min. image this wavelength using 5 sec. raster steps takes about 3 minutes. UVSP can also make observations of the Sun at approx. wavelength of 2790 with 3 sec. spatial resolution when operated in its 1st-order mode; a full-field image at this wavelength (a so-called SNEW image) takes about 8 minutes. UVSP made thousands of observations (mostly in 2nd-order) of AR 5395 during its transit across the visible solar hemisphere (from 7 to 19 March, inclusive). During this period, UVSP's duty cycle for observing AR 5395 was roughly 40 percent, with the remaining 60 percent of the time being fairly evenly divided between aeronomy studies of the Earth's atmosphere and dead time due to Earth occultation of the Sun. UVSP observed many of the flares tagged to AR 5395, including 26 GOES M-level flares and 3 X-level flares, one of which produced so much UV emission that the safety software of UVSP turned off the detector to avoid damage due to saturation. Images and light curves of some of the more spectacular of the AR 5395 events are presented.

Modulations of the surface magnetic field on the intra-cycle variability of total solar irradiance

NASA Astrophysics Data System (ADS)

Xu, J. C.; Kong, D. F.; Li, F. Y.

2018-05-01

Solar photospheric magnetic field plays a dominant role in the variability of total solar irradiance (TSI). The modulation of magnetic flux at six specific ranges on TSI is characterized for the first time. The daily flux values of magnetic field at four ranges are extracted from MDI/ SOHO, together with daily flux of active regions (MF_{ar}) and quiet regions (MF_{qr}); the first four ranges (MF_{1-4}) are: 1.5-2.9, 2.9-32.0, 32.0-42.7, and 42.7-380.1 (× 10^{18} Mx per element), respectively. Cross-correlograms show that MF4, MF_{qr}, and MF_{ ar} are positively correlated with TSI, while MF2 is negatively correlated with TSI; the correlations between MF1, MF3 and TSI are insignificant. The bootstrapping tests confirm that the impact of MF4 on TSI is more significant than that of MF_{ar} and MF_{qr}, and MF_{ar} leads TSI by one rotational period. By extracting the rotational variations in the MFs and TSI, the modulations of the former on the latter at the solar rotational timescale are clearly illustrated and compared during solar maximum and minimum times, respectively. Comparison of the relative amplitudes of the long-term variation show that TSI is in good agreement with the variation of MF4 and MF_{ar}; besides, MF2 is in antiphase with TSI, and it lags the latter by about 1.5 years.

Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells

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

Sun, Shaowei; Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan; Wen, Juan

Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626–740 clearly reduced intracellular cholesterol levels and inhibited the expressionmore » of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626–740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells. - Highlights: • Daxx C-terminal domain reduces cholesterol levels. • Daxx C-terminal domain binds directly to AR. • The interaction of Daxx C-terminal domain and AR suppresses cholesterol synthesis.« less

PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signaling in cardiac myocytes.

PubMed

Bedioune, Ibrahim; Lefebvre, Florence; Lechêne, Patrick; Varin, Audrey; Domergue, Valérie; Kapiloff, Michael S; Fischmeister, Rodolphe; Vandecasteele, Grégoire

2018-05-03

β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes. We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation. Both β1- and β2-AR stimulation increased cAMP and activated PKA in the cytoplasm. While the two receptors also increased cAMP in the nucleus, only β1-ARs increased nuclear PKA activity and up-regulated the PKA target gene and pro-apoptotic factor, inducible cAMP element repressor (ICER). Inhibition of PDE4, but not Gi, PDE3, GRK2 nor caveolae disruption disclosed nuclear PKA activation and ICER induction by β2-ARs. Both nuclear and cytoplasmic PKI prevented nuclear PKA activation and ICER induction by β1-ARs, indicating that PKA activation outside the nucleus is required for subsequent nuclear PKA activation and ICER mRNA expression. Cytoplasmic PKI also blocked ICER induction by β2-AR stimulation (with concomitant PDE4 inhibition). However, in this case nuclear PKI decreased ICER up-regulation by only 30%, indicating that other mechanisms are involved. Down-regulation of mAKAPβ partially inhibited nuclear PKA activation upon β1-AR stimulation, and drastically decreased nuclear PKA activation upon β2-AR stimulation in the presence of PDE4 inhibition. β1- and β2-ARs differentially regulate nuclear PKA activity and ICER expression in cardiomyocytes. PDE4 insulates a mAKAPβ-targeted PKA pool at the nuclear envelope that prevents nuclear PKA activation upon β2-AR stimulation.

Inappropriate activation of the androgen receptor by nonsteroids: involvement of the Src kinase pathway and its therapeutic implications.

PubMed

Desai, Sonal J; Ma, Ai-Hong; Tepper, Clifford G; Chen, Hong-Wu; Kung, Hsing-Jien

2006-11-01

The inappropriate activation of androgen receptor (AR) by nonsteroids is considered a potential mechanism in the emergence of hormone-refractory prostate tumors, but little is known about the properties of these "pseudoactivated" AR. Here, we present the first comprehensive analysis closely examining the properties of AR activated by the neuropeptide bombesin that distinguish it from androgen-activated AR. We show that bombesin-activated AR (a) is required for bombesin-induced growth of LNCaP cells, (b) has a transcriptional profile overlapping with, but not identical to, androgen-activated AR, (c) activates prostate-specific antigen by preferentially binding to its proximal promoter, and (d) assembles a distinct coactivator complex. Significantly, we found that Src kinase is critical for bombesin-induced AR-mediated activity and is required for translocation and transactivation of AR. Additionally, we identify c-Myc, a Src target gene, to be activated by bombesin and a potential coactivator of AR-mediated activity specific to bombesin-induced signaling. Because Src kinase is often activated by other nonsteroids, such as other neuropeptides, growth factors, chemokines, and cytokines, our findings have general applicability and provide rationale for investigating the efficacy of the Src kinase pathway as a target for the prevention of relapsed prostate cancers.

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

Perceived moral traits of others differentiate the neural activation that underlies inequity-aversion

PubMed Central

Nakatani, Hironori; Ogawa, Akitoshi; Suzuki, Chisato; Asamizuya, Takeshi; Ueno, Kenichi; Cheng, Kang; Okanoya, Kazuo

2017-01-01

We have a social preference to reduce inequity in the outcomes between oneself and others. Such a preference varies according to others. We performed functional magnetic resonance imaging during an economic game to investigate how the perceived moral traits of others modulate the neural activities that underlie inequity-aversion. The participants unilaterally allocated money to three partners (good, neutral, and bad). During presentation of the good and neutral partners, the anterior region of the rostral medial frontal cortex (arMFC) showed increased functional connectivity with the caudate head and the anterior insula, respectively. Following this, participants allocated more money to the good partner, and less to the bad partner, compared with the neutral partner. The caudate head and anterior insula showed greater activation during fair allocation to the good and unfair allocation to the neutral partners, respectively. However, these regions were silent during allocations to the bad partner. Therefore, the arMFC-caudate/insula circuit encompasses distinct neural processes that underlie inequity-aversion in monetary allocations that the different moral traits of others can modulate. PMID:28230155

INVESTIGATION OF HELICITY AND ENERGY FLUX TRANSPORT IN THREE EMERGING SOLAR ACTIVE REGIONS

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

Vemareddy, P., E-mail: vemareddy@iiap.res.in

We report the results of an investigation of helicity and energy flux transport from three emerging solar active regions (ARs). Using time sequence vector magnetic field observations obtained from the Helioseismic Magnetic Imager, the velocity field of plasma flows is derived by the differential affine velocity estimator for vector magnetograms. In three cases, the magnetic fluxes evolve to pump net positive, negative, and mixed-sign helicity flux into the corona. The coronal helicity flux is dominantly coming from the shear term that is related to horizontal flux motions, whereas energy flux is dominantly contributed by the emergence term. The shear helicity fluxmore » has a phase delay of 5–14 hr with respect to absolute magnetic flux. The nonlinear curve of coronal energy versus relative helicity identifies the configuration of coronal magnetic fields, which is approximated by a fit of linear force-free fields. The nature of coronal helicity related to the particular pattern of evolving magnetic fluxes at the photosphere has implications for the generation mechanism of two kinds of observed activity in the ARs.« less

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).

Cooling, exhumation, and deformation in the Hindu Kush, NW Pakistan: New constraints from preliminary 40Ar/39Ar and fission track analyses

NASA Astrophysics Data System (ADS)

Faisal, Shah; Larson, Kyle P.; Camacho, Alfredo; Coutand, Isabelle

2018-06-01

Asian crust in the Hindu Kush region in northern Pakistan records a protracted history of rifting, subduction and collision not commonly preserved within the Himalaya. Because of this, it is key to understanding the development of the southern Eurasian margin both prior to and after collision with India. New mica 40Ar/39Ar and apatite fission track geochronologic data from this region provide constraints on the kinematics of the Hindu Kush. 40Ar/39Ar muscovite and biotite ages from the late Cambrian Kafiristan pluton are 379.7 ± 1.7 Ma and 47.2 ± 0.3 Ma, respectively. The muscovite age may record cooling or partial resetting, while the biotite age is interpreted to record a thermal disruption associated with the early stages of continental collision in the Himalayan system. A 111.0 ± 0.6 Ma muscovite age from the northern part of the Tirich Mir pluton (∼123 Ma old; U-Pb) is interpreted to indicate a recrystallization event ∼12 Myrs after its intrusion. In addition, a younger muscovite age of 47.5 ± 0.2 Ma was derived from the opposite side of the same pluton in the immediate hanging wall of the Tirich Mir fault. This Eocene age is interpreted to represent the time of recrystallization during fault (re)activation in the early stages of India-Asia continent-continent collision. 40Ar/39Ar biotite analysis from the Buni-Zom pluton yields an age of 61.6 ± 1.1 Ma and is interpreted to reflect cooling at mid-upper crustal levels subsequent to the pluton's emplacement in the middle Cretaceous. Finally, 17.1-21.3 Ma 40Ar/39Ar ages from the Garam Chasma pluton and surrounding metapelites indicate cooling immediately following crystallization of the leucogranite body in the earliest Miocene/latest Oligocene. The younger cooling history is resolved by fission track dating of apatite (AFT). In the vicinity of the bounding Tirich Mir fault, the Tirich Mir pluton yields an AFT age of 1.4 ± 0.3 Ma, which is consistent with active exhumation associated with the surface uplift of the 7700+ m Tirich Mir peak. The Garam Chasma pluton has a young age of 3.5 ± 0.2 Ma, which also records rapid rock uplift and exhumation in the area. Finally, an AFT age of 9.1 ± 2.1 Ma was extracted from a metapelite in the footwall of an east verging thrust fault separating it from the Garam Chasma pluton to the west. The difference in ages, Pliocene vs. late Miocene, reflect differential cooling/exhumation paths across that structure.

Properties of quasi-periodic pulsations in solar flares from a single active region

NASA Astrophysics Data System (ADS)

Pugh, C. E.; Nakariakov, V. M.; Broomhall, A.-M.; Bogomolov, A. V.; Myagkova, I. N.

2017-12-01

Context. Quasi-periodic pulsations (QPPs) are a common feature of solar and stellar flares, and so the nature of these pulsations should be understood in order to fully understand flares. Aims: We investigate the properties of a set of solar flares originating from a single active region (AR) that exhibit QPPs, and in particular look for any indication of QPP periods relating to AR properties, as might be expected if the characteristic timescale of the pulsations corresponds to a characteristic length scale of the structure from which the pulsations originate. The three AR properties used for this study are the photospheric area, bipole separation distance, and average magnetic field strength at the photosphere. The AR studied, known as NOAA 12172/12192/12209, was unusually long-lived and persisted for over three Carrington rotations between September and November 2014. During this time a total of 181 flares were observed by GOES. Methods: Data from the GOES/XRS, SDO/EVE/ESP, Fermi/GBM, Vernov/DRGE and Nobeyama Radioheliograph observatories were used to determine if QPPs were present in the flares. For the soft X-ray GOES/XRS and EVE/ESP data, the time derivative of the signal was used so that any variability in the impulsive phase of the flare was emphasised. Periodogram power spectra of the time series data, without any form of detrending, were inspected and flares with a peak above the 95% confidence level in the power spectrum were labelled as having candidate QPPs. The confidence levels were determined taking full account of data uncertainties and the possible presence of red noise. Active region properties were determined using SDO/HMI line of sight magnetogram data. Results: A total of 37 flares, i.e. 20% of the sample, show good evidence of having stationary or weakly non-stationary QPPs, and some of the pulsations can be seen in data from multiple instruments and in different wavebands. Because the detection method used was rather conservative, this may be a lower bound for the true number of flares with QPPs. The QPP periods were found to show a weak correlation with the flare amplitude and duration, but this is likely due to an observational bias. A stronger correlation was found between the QPP period and duration of the QPP signal, which can be partially but not entirely explained by observational constraints. No correlations were found with the AR area, bipole separation distance, or average magnetic field strength. Conclusions: The fact that a substantial fraction of the flare sample showed evidence of QPPs, using a strict detection method with minimal processing of the data, demonstrates that these QPPs are a real phenomenon that cannot be explained by the presence of red noise or the superposition of multiple unrelated flares. The lack of correlation between the QPP periods and AR properties implies that the small-scale structure of the AR is important and/or that different QPP mechanisms act in different cases.

A quantity characterizing variation of observed magnetic twist in solar active regions

NASA Astrophysics Data System (ADS)

Gao, Yu

2018-03-01

An alternative parameter RJz is introduced as the ratio of one of two kinds of opposite-sign current to the total current and is used to investigate the relationship between this quantity and the hemispheric helicity sign rule (HSR) that has been established by a series of previous statistical studies. The classification of current in each hemisphere obeys the following rule: if the product of the current and the corresponding longitudinal field component contributes a consistent sign with respect to the HSR, it is called “HSR-compliant” current, otherwise it is called “HSR-noncompliant” current. Firstly, consistency between the butterfly diagram of RJz and current helicity was obtained in a statistical study. Active regions with RJz smaller than 0.5 tend to obey the HSR whereas those with RJz greater than 0.5 tend to disobey it. The “HSR-compliant” current systems have a 60% probability of realization compared to 40% for “HSR-noncompliant” current systems. Overall, the HSR is violated for active regions in which the “HSR-noncompliant” current is greater than the “HSR-compliant” current. Secondly, the parameter RJz was subsequently used to study the evolution of current systems in the case analyses of flare-productive active regions NOAA AR 11158 and AR 11283. It is found that there is a “RJz -quasi-stationary” phase that is relatively flare quiescent and “RJz -dynamic” phase that is characterized by the occurrence of large flares.

Regional Stewardship and the Redefinition of Higher Education

ERIC Educational Resources Information Center

Simpson, Timothy Leahy

2010-01-01

Inspired by the late John Gardner, in May 2000 the "Alliance for Regional Stewardship" (ARS) was formed as a "peer-to-peer network of regional leaders working across boundaries to solve tough community problems." According to the ARS, regional stewardship is the leadership needed to address the complex problems of one's time.…

Transformation of vector magnetograms and the problems associated with the effects of perspective and the azimuthal ambiguity

NASA Technical Reports Server (NTRS)

Gary, G. Allen; Hagyard, M. J.

1990-01-01

Off-center vector magnetograms which use all three components of the measured field provide the maximum information content from the photospheric field and can provide the most consistent potential field independent of the viewing angle by defining the normal component of the field. The required transformations of the magnetic field vector and the geometric mapping of the observed field in the image plane into the heliographic plane have been described. Here we discuss the total transformation of specific vector magnetograms to detail the problems and procedures that one should be aware of in analyzing observational magnetograms. The effect of the 180-deg ambiguity of the observed transverse field is considered as well as the effect of curvature of the photosphere. Specific results for active regions AR 2684 (September 23, 1980) and AR 4474 (April 26, 1984) from the Marshall Space Flight Center Vector magnetograph are described which point to the need for the heliographic projection in determining the field structure of an active region.

A Search for Vector Magnetic Field Variations Associated with the M-Class Flares of 1991 June 10 in AR 6659

NASA Technical Reports Server (NTRS)

Hagyard, Mona J.; Stark, B. A.; Venkatakrishnan, P.

1998-01-01

A careful analysis of a 6-hour time sequence of vector magnetograms of AR 6659, observed on 1991 June 10 with the MSFC vector magnetograph, has revealed only minor changes in the vector magnetic field azimuths in the vicinity of two M-class flares, and the association of these changes with the flares is not unambiguous. In this paper we present our analysis of the data which includes comparison of vector magnetograms prior to and during the flares, calculation of distributions of the rms variation of the azimuth at each pixel in the field of view of the active region, and examination of the variation with time of the azimuths at every pixel covered by the main flare emissions as observed with the H-alpha telescope coaligned with the vector magnetograph. We also present results of an analysis of evolutionary changes in the azimuth over the field of view of the active region.

Coordinated Observations of AR 11726 by Hinode/EIS and EUNIS-2013

NASA Astrophysics Data System (ADS)

Ancheta, A. J.; Daw, A. N.; Brosius, J. W.

2016-12-01

The Extreme-Ultraviolet Normal-Incidence Spectrograph (EUNIS) sounding rocket payload was flown on 2013 April 23 with two independent channels covering the 300-370 A and 525-635 A wavebands. EUNIS-2013 observed two targets on the solar disk that included quiet sun, active regions, a flare, and a micro-flare. The active region AR 11726 was co-observed with the EUV Imaging Spectrometer (EIS) on Hinode. The radiometric response of EUNIS is measured in the laboratory using a NIST-calibrated photodiode and hollow cathode discharge lamp. A density- and temperature- insensitive line intensity ratio technique can be used to derive an in-flight calibration update of Hinode/EIS. Measurements of EIS emission lines with respect to EUNIS lines, including Fe X to Fe XII and Si X, provide a comparison between the calibrations of the two instruments. The radiometric calibration of EUNIS-2013 is also validated using the same insensitive ratio technique with emission lines such as Mg VIII, Fe XI, Fe XVI, and Si IX.

[Health education in the French Regional Health Agencies in 2012: observations and analysis].

PubMed

Baudier, François; Destaing, Lara; Michaud, Claude

2013-01-01

This paper examines the role of health education in the French Agences régionales de santé (ARS, Regional Health Agencies) in 2012. A survey was conducted among public health managers working in the ARS. Most of the participants reported that health education plays an important role in their agency, notably through their regional health plan and the activities of the organizations responsible for promoting democracy in health care. This is also true of the links with the Institut national de prévention et d'education pour la santé (INPES, the National Institute for Health Prevention and Education) and the network of Instances régionales d'éducation et de promotion de la santé (IREPS, the Regional Authorities for Health Education and Promotion). However, the answers to the open-ended questions and the results of the interviews suggest that these results must be interpreted with caution. The study focuses on a number of factors that must be taken into account when considering the results of the quantitative analysis. These factors include: the subjective (or interpretive) dimension of the term "health education" emphasized by many of the participants (a term involving an emphasis on either health promotion or preventive medicine); the limited emphasis on health education in the ARS (beyond therapeutic patient education) compared to other issues such as health monitoring and security, health care and medico-social problems; the limited resources allocated to health education and the bleak budget outlook; the relationships with the main operators; and the need to develop, promote and apply knowledge of good practice. Finally, the study shows that the role of health education is dependent on individuals' willingness to promote it and, in particular, on the commitment of ARS managers.

Seasonal changes and sexual dimorphism in gene expression of StAR protein, steroidogenic enzymes and sex hormone receptors in the frog brain.

PubMed

Santillo, Alessandra; Falvo, Sara; Di Fiore, Maria Maddalena; Chieffi Baccari, Gabriella

2017-05-15

The brain of amphibians contains all the key enzymes of steroidogenesis and has a high steroidogenic activity. In seasonally-breeding amphibian species brain steroid levels fluctuate synchronously with the reproductive cycle. Here we report a study of gene expression of StAR protein, key steroidogenic enzymes and sex hormone receptors in the telencephalon (T) and diencephalon-mesencephalon (D-M) of male and female reproductive and post-reproductive Pelophylax esculentus, a seasonally breeding anuran amphibian. Significant differences in gene expression were observed between (a) the reproductive and post-reproductive phase, (b) the two brain regions and (c) male and female frogs. During the reproductive phase, star gene expression increased in the male (both T and D-M) but not in the female brain. Seasonal fluctuations in expression levels of hsd3b1, hsd17b1, srd5a1 and cyp19a1 genes for neurosteroidogenic enzymes occurred in D-M region of both sexes, with the higher levels in reproductive period. Moreover, the D-M region generally showed higher levels of gene expression than the T region in both sexes. Gene expression was higher in females than males for most genes, suggesting higher neurosteroid production in female brain. Seasonal and sex-linked changes were also observed in gene expression for androgen (ar) and estrogen (esr1, esr2) receptors, with the males showing the highest ar levels in reproductive phase and the highest esr1 and esr2 levels in post-reproductive phase; in contrast, females showed the maximum expression for all three genes in reproductive phase. The results are the first evidence for seasonal changes and sexual dimorphism of gene expression of the neurosteroidogenic pathway in amphibians. Copyright © 2016 Elsevier Inc. All rights reserved.

HOMOLOGOUS JET-DRIVEN CORONAL MASS EJECTIONS FROM SOLAR ACTIVE REGION 12192

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

Panesar, Navdeep K.; Sterling, Alphonse C.; Moore, Ronald L., E-mail: navdeep.k.panesar@nasa.gov

We report observations of homologous coronal jets and their coronal mass ejections (CMEs) observed by instruments onboard the Solar Dynamics Observatory (SDO) and the Solar and Heliospheric Observatory (SOHO) spacecraft. The homologous jets originated from a location with emerging and canceling magnetic field at the southeastern edge of the giant active region (AR) of 2014 October, NOAA 12192. This AR produced in its interior many non-jet major flare eruptions (X- and M- class) that made no CME. During October 20 to 27, in contrast to the major flare eruptions in the interior, six of the homologous jets from the edgemore » resulted in CMEs. Each jet-driven CME (∼200–300 km s{sup −1}) was slower-moving than most CMEs, with angular widths (20°–50°) comparable to that of the base of a coronal streamer straddling the AR and were of the “streamer-puff” variety, whereby the preexisting streamer was transiently inflated but not destroyed by the passage of the CME. Much of the transition-region-temperature plasma in the CME-producing jets escaped from the Sun, whereas relatively more of the transition-region plasma in non-CME-producing jets fell back to the solar surface. Also, the CME-producing jets tended to be faster and longer-lasting than the non-CME-producing jets. Our observations imply that each jet and CME resulted from reconnection opening of twisted field that erupted from the jet base and that the erupting field did not become a plasmoid as previously envisioned for streamer-puff CMEs, but instead the jet-guiding streamer-base loop was blown out by the loop’s twist from the reconnection.« less

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

NASA Astrophysics Data System (ADS)

Duan, Aiying; Jiang, Chaowei; Hu, Qiang; Zhang, Huai; Gary, G. Allen; Wu, S. T.; Cao, Jinbin

2017-06-01

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE-MHD-NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from the region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO/AIA. It is found that the CESE-MHD-NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ˜10°. This suggests that the CESE-MHD-NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (˜30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.

A comparison study of a solar active-region eruptive filament and a neighboring non-eruptive filament

NASA Astrophysics Data System (ADS)

Jiang, Chao-Wei; Wu, Shi-Tsan; Feng, Xue-Shang; Hu, Qiang

2016-01-01

Solar active region (AR) 11283 is a very magnetically complex region and it has produced many eruptions. However, there exists a non-eruptive filament in the plage region just next to an eruptive one in the AR, which gives us an opportunity to perform a comparison analysis of these two filaments. The coronal magnetic field extrapolated using our CESE-MHD-NLFFF code reveals that two magnetic flux ropes (MFRs) exist in the same extrapolation box supporting these two filaments, respectively. Analysis of the magnetic field shows that the eruptive MFR contains a bald-patch separatrix surface (BPSS) cospatial very well with a pre-eruptive EUV sigmoid, which is consistent with the BPSS model for coronal sigmoids. The magnetic dips of the non-eruptive MFRs match Hα observation of the non-eruptive filament strikingly well, which strongly supports the MFR-dip model for filaments. Compared with the non-eruptive MFR/filament (with a length of about 200 Mm), the eruptive MFR/filament is much smaller (with a length of about 20 Mm), but it contains most of the magnetic free energy in the extrapolation box and holds a much higher free energy density than the non-eruptive one. Both the MFRs are weakly twisted and cannot trigger kink instability. The AR eruptive MFR is unstable because its axis reaches above a critical height for torus instability, at which the overlying closed arcades can no longer confine the MFR stably. On the contrary, the quiescent MFR is very firmly held by its overlying field, as its axis apex is far below the torus-instability threshold height. Overall, this comparison investigation supports that an MFR can exist prior to eruption and the ideal MHD instability can trigger an MFR eruption.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

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

Duan, Aiying; Zhang, Huai; Jiang, Chaowei

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE–MHD–NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from themore » region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO /AIA. It is found that the CESE–MHD–NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ∼10°. This suggests that the CESE–MHD–NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (∼30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.« less

Practice Patterns for Chronic Respiratory Diseases in the Asia-Pacific Region: A Cross-Sectional Observational Study.

PubMed

Wang, De Yun; Cho, Sang-Heon; Lin, Horng-Chyuan; Ghoshal, Aloke Gopal; Bin Abdul Muttalif, Abdul Razak; Thanaviratananich, Sanguansak; Tunceli, Kaan; Urdaneta, Eduardo; Zhang, Dongmu; Faruqi, Rab

2018-06-06

Allergic rhinitis (AR), asthma, chronic obstructive pulmonary disease (COPD), and rhinosinusitis are common and little studied in the Asia-Pacific region. We sought to investigate real-world practice patterns for these respiratory diseases in India, Korea, Malaysia, Singapore, Taiwan, and Thailand. This cross-sectional observational study enrolled adults (age ≥18 years) presenting to general practitioners (GP) or specialists for physician-diagnosed AR, asthma, COPD, or rhinosinusitis. Physicians and patients completed study-specific surveys at one visit, recording patient characteristics, health-related quality of life (QoL), work impairment, and healthcare resource use. Findings by country and physician category (GP or specialist) were summarized. Of the 13,902 patients screened, 7,243 (52%) presented with AR (18%), asthma (18%), COPD (7%), or rhinosinusitis (9%); 5,250 of the 7,243 (72%) patients were eligible for this study. Most eligible patients (70-100%) in India, Korea, Malaysia, and Singapore attended GP, while most (83-85%) in Taiwan and Thailand attended specialists. From 42% (rhinosinusitis) to 67% (AR) of new diagnoses were made by GP. On average, patients with COPD reported the worst health-related QoL, particularly to GP. Median losses of work productivity for each condition and activity impairment, except for asthma, were numerically greater for patients presenting to GP vs. specialists. GP prescribed more antibiotics for AR and asthma, and fewer intranasal corticosteroids for AR, than specialists (p < 0.001 for all comparisons). Our findings, albeit mostly descriptive and influenced by between-country differences, suggest that practice patterns differ between physician types, and the disease burden may be substantial for patients presenting in general practice. © 2018 S. Karger AG, Basel.

Global Floods and Water Availability Driven by Atmospheric Rivers

NASA Astrophysics Data System (ADS)

Paltan, Homero; Waliser, Duane; Lim, Wee Ho; Guan, Bin; Yamazaki, Dai; Pant, Raghav; Dadson, Simon

2017-10-01

While emerging regional evidence shows that atmospheric rivers (ARs) can exert strong impacts on local water availability and flooding, their role in shaping global hydrological extremes has not yet been investigated. Here we quantify the relative contribution of ARs variability to both flood hazard and water availability. We find that globally, precipitation from ARs contributes 22% of total global runoff, with a number of regions reaching 50% or more. In areas where their influence is strongest, ARs may increase the occurrence of floods by 80%, while absence of ARs may increase the occurrence of hydrological droughts events by up to 90%. We also find that 300 million people are exposed to additional floods and droughts due the occurrence of ARs. ARs provide a source of hydroclimatic variability whose beneficial or damaging effects depend on the capacity of water resources managers to predict and adapt to them.

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

Association of Supergranule Mean Scales with Solar Cycle Strengths and Total Solar Irradiance

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

Mandal, Sudip; Chatterjee, Subhamoy; Banerjee, Dipankar, E-mail: sudip@iiap.res.in

We analyze the long-term behavior of the supergranule scale parameter, in active regions (ARs) and quiet regions (QRs), using the Kodaikanal digitized data archive. This database provides century-long daily full disk observations of the Sun in Ca ii K wavelengths. In this paper, we study the distributions of the supergranular scales, over the whole data duration, which show identical shape in these two regimes. We found that the AR mean scale values are always higher than that of the QR for every solar cycle. The mean scale values are highly correlated with the sunspot number cycle amplitude and also withmore » total solar irradiance (TSI) variations. Such a correlation establishes the cycle-wise mean scale as a potential calibrator for the historical data reconstructions. We also see an upward trend in the mean scales, as has already been reported in TSI. This may provide new input for climate forcing models. These results also give us insight into the different evolutionary scenarios of the supergranules in the presence of strong (AR) and weak (QR) magnetic fields.« less

Association of Supergranule Mean Scales with Solar Cycle Strengths and Total Solar Irradiance

NASA Astrophysics Data System (ADS)

Mandal, Sudip; Chatterjee, Subhamoy; Banerjee, Dipankar

2017-07-01

We analyze the long-term behavior of the supergranule scale parameter, in active regions (ARs) and quiet regions (QRs), using the Kodaikanal digitized data archive. This database provides century-long daily full disk observations of the Sun in Ca II K wavelengths. In this paper, we study the distributions of the supergranular scales, over the whole data duration, which show identical shape in these two regimes. We found that the AR mean scale values are always higher than that of the QR for every solar cycle. The mean scale values are highly correlated with the sunspot number cycle amplitude and also with total solar irradiance (TSI) variations. Such a correlation establishes the cycle-wise mean scale as a potential calibrator for the historical data reconstructions. We also see an upward trend in the mean scales, as has already been reported in TSI. This may provide new input for climate forcing models. These results also give us insight into the different evolutionary scenarios of the supergranules in the presence of strong (AR) and weak (QR) magnetic fields.

Propagating wave in active region-loops, located over the solar disk observed by the Interface Region Imaging Spectrograph

NASA Astrophysics Data System (ADS)

Zhang, B.; Hou, Y. J.; Zhang, J.

2018-03-01

Aims: We aim to ascertain the physical parameters of a propagating wave over the solar disk detected by the Interface Region Imaging Spectrograph (IRIS). Methods: Using imaging data from the IRIS and the Solar Dynamic Observatory (SDO), we tracked bright spots to determine the parameters of a propagating transverse wave in active region (AR) loops triggered by activation of a filament. Deriving the Doppler velocity of Si IV line from spectral observations of IRIS, we have determined the rotating directions of active region loops which are relevant to the wave. Results: On 2015 December 19, a filament was located on the polarity inversion line of the NOAA AR 12470. The filament was activated and then caused a C1.1 two-ribbon flare. Between the flare ribbons, two rotation motions of a set of bright loops were observed to appear in turn with opposite directions. Following the end of the second rotation, a propagating wave and an associated transverse oscillation were detected in these bright loops. In 1400 Å channel, there was bright material flowing along the loops in a wave-like manner, with a period of 128 s and a mean amplitude of 880 km. For the transverse oscillation, we tracked a given loop and determine the transverse positions of the tracking loop in a limited longitudinal range. In both of 1400 Å and 171 Å channels, approximately four periods are distinguished during the transverse oscillation. The mean period of the oscillation is estimated as 143 s and the displacement amplitude as between 1370 km and 690 km. We interpret these oscillations as a propagating kink wave and obtain its speed of 1400 km s-1. Conclusions: Our observations reveal that a flare associated with filament activation could trigger a kink propagating wave in active region loops over the solar disk. Movies associated to Figs. 1-4 are available at http://https://www.aanda.org

Low and declining attack rates of imported typhoid fever in the Netherlands 1997-2014, in spite of a restricted vaccination policy.

PubMed

Suryapranata, F S T; Prins, M; Sonder, G J B

2016-12-01

Typhoid fever mainly occurs in (sub) tropical regions where sanitary conditions remain poor. In other regions it occurs mainly among returning travelers or their direct contacts. The aim of this study was to evaluate the current Dutch guidelines for typhoid vaccination. Crude annual attack rates (AR) per 100,000 Dutch travelers were calculated during the period 1997 to 2014 by dividing the number of typhoid fever cases by the estimated total number of travelers to a specific country or region. Regions of exposure and possible risk factors were evaluated. During the study period 607 cases of typhoid fever were reported. Most cases were imported from Asia (60%). Almost half of the cases were ethnically related to typhoid risk regions and 37% were cases visiting friends and relatives. The overall ARs for travelers to all regions declined significantly. Countries with the highest ARs were India (29 per 100,000), Indonesia (8 per 100,000), and Morocco (10 per 100,000). There was a significant decline in ARs among travelers to popular travel destinations such as Morocco, Turkey, and Indonesia. ARs among travelers to intermediate-risk areas according to the Dutch guidelines such as Latin America or Sub-Saharan Africa remained very low, despite the restricted vaccination policy for these areas compared to many other guidelines. The overall AR of typhoid fever among travelers returning to the Netherlands is very low and has declined in the past 20 years. The Dutch vaccination policy not to vaccinate short-term travelers to Latin-America, Sub-Saharan Africa, Thailand and Malaysia seems to be justified, because the ARs for these destinations remain very low. These results suggest that further restriction of the Dutch vaccination policy is justified.

Electrically-driven pure amplitude and frequency modulation in a quantum cascade laser.

PubMed

Shehzad, Atif; Brochard, Pierre; Matthey, Renaud; Blaser, Stéphane; Gresch, Tobias; Maulini, Richard; Muller, Antoine; Südmeyer, Thomas; Schilt, Stéphane

2018-04-30

We present pure amplitude modulation (AM) and frequency modulation (FM) achieved electrically in a quantum cascade laser (QCL) equipped with an integrated resistive heater (IH). The QCL output power scales linearly with the current applied to the active region (AR), but decreases with the IH current, while the emission frequency decreases with both currents. Hence, a simultaneous modulation applied to the current of the AR and IH sections with a proper relative amplitude and phase can suppress the AM, resulting in a pure FM, or vice-versa. The adequate modulation parameters depend on the applied modulation frequency. Therefore, they were first determined from the individual measurements of the AM and FM transfer functions obtained for a modulation applied to the current of the AR or IH section, respectively. By optimizing the parameters of the two modulations, we demonstrate a reduction of the spurious AM or FM by almost two orders of magnitude at characteristic frequencies of 1 and 10 kHz compared to the use of the AR current only.

Independent CMEs from a Single Solar Active Region - The Case of the Super-Eruptive NOAA AR11429

NASA Astrophysics Data System (ADS)

Chintzoglou, Georgios; Patsourakos, Spiros; Vourlidas, Angelos

2014-06-01

In this investigation we study AR 11429, the origin of the twin super-fast CME eruptions of 07-Mar-2012. This AR fulfills all the requirements for the 'perfect storm'; namely, Hale's law incompatibility and a delta-magnetic configuration. In fact, during its limb-to-limb transit, AR 11429 spawned several eruptions which caused geomagnetic storms, including the biggest in Cycle 24 so far. Magnetic Flux Ropes (MFRs) are twisted magnetic structures in the corona, best seen in ~10MK hot plasma emission and are often considered as the culprit causing such super-eruptions. However, their 'dormant' existence in the solar atmosphere (i.e. prior to eruptions), is a matter of strong debate. Aided by multi-wavelength and multi-spacecraft observations (SDO/HMI & AIA, HINODE/SOT/SP, STEREO B/EUVI) and by using a Non-Linear Force-Free (NLFFF) model for the coronal magnetic field, our work shows two separate, weakly-twisted magnetic flux systems which suggest the existence of possible pre-eruption MFRs.

UV and X-ray Evolution of AR12230 as Observed with IRIS and FOXSI-II

NASA Astrophysics Data System (ADS)

Ryan, Daniel; Christe, Steven; Glesener, Lindsay; Vievering, Julie; Krucker, Sam; Ishikawa, Shin-Nosuke

2017-08-01

We present a multi-spectral and spatio-temporal analysis of AR12230 using both UV and X-ray spectroscopic imaging obtained as part of a coordinated observing campaign on 11 December 2014. The campaign involved IRIS (Interface Region Imaging Spectrometer) -- which provides both UV imaging and slit spectrograph observations of optically thick chromospheric and transition region emission -- and FOXSI-II (Focusing Optics X-ray Solar Imager) -- the second in a series of sounding rocket flights which combines grazing incidence direct focusing optics to produce solar X-ray spectroscopic imaging in the range 4-15keV. The active region exhibits a prolonged compact brightening in the IRIS 1330 A and 1400 A slit-jaw channels near the center of the active region throughout the duration of the observations. In the early phase of the observations FOXSI-II shows an X-ray source approximately 20x20 arcsec centered at the same location. The X-ray spectra show the presence of hot (~8 MK) thermal plasma and is suggestive of the presence of non-thermal electrons.. Later, two additional transient, spatially extended, simultaneous brightenings are observed, one of which was captured by the IRIS slit spectrograph. We combine these observations to explore the evolution and topology of the active region. Hydrodynamic modeling of the chromosphere is used to place a limit on the amount of non-thermal electrons required to produce the observed UV emission. This result is then compared to the limit inferred from the FOXSI-II X-ray spectra. Thus, we explore the role of non-thermal electrons and hydrodynamics in the energization and evolution of plasma in active regions.

Hi-C Observations of an Active Region Corona, and Investigation of the Underlying Magnetic Structure

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Alexander, Caroline E.; Winebarger, Amy R.; Moore, Ronald L.

2014-01-01

Hi-C: first observational evidence of field line braiding in the AR corona; NLFFF extrapolations support. Flux emergence and/or cancellation in the coronal braided region generate large stresses and tension in the coronal field loops which is released as heat in the corona. The field in these sub-regions are highly sheared and have apparent high speed plasma flows, therefore, the contribution from shearing flows to power the coronal and transition region heating can not be ruled out! The spatial resolution of Hi-­C is five times better than AIA. The cadence of Hi-C is 2.5 - 6 times better than AIA. The 193 Å was selected because of the strong emission line of Fe XII (peak formation temperature of 1.5 MK). Hi-­C collected data for 345 s @ 5.4 s cadence. The Hi-C target region was NOAA AR 11520; 11 July 2012, 18:51-18:57 UT. NLFFF extrapolation confirms the braided structure, and free magnetic energy estimates in the given volume.

Evaluation of partial beta-adrenoceptor agonist activity.

PubMed

Lipworth, B J; Grove, A

1997-01-01

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

Multistage extensional evolution of the central East Greenland Caledonides

NASA Astrophysics Data System (ADS)

White, Arthur P.; Hodges, Kip V.

2002-10-01

Recent field investigations in the central East Greenland Caledonides (72°-74°N) resulted in the identification of an orogen-scale extensional fault system called the Fjord Region Detachment (FRD). Previous geochronologic constraints on this deformation indicated that the FRD was active circa 430-425 Ma, a time when the Baltica-Laurentia collision was thought to be occurring, and continued to be active for up to 80 million years. We present new 40Ar/39Ar thermochronologic data from an E-W transect that cuts across two splays of the FRD. Our data demonstrate that at least two distinct episodes of faulting were responsible for extension in the East Greenland Caledonides: an earlier phase (circa 425-423 Ma) that was synorogenic and penetrated to middle-crustal levels, followed by a post-Caledonian phase of reactivation (˜414 to 380 Ma) that affected even deeper structural levels. Furthermore, we present in situ UV laser 40Ar/39Ar data for pseudotachylite collected along the deepest splay of the FRD that indicate this fault was active again as recently as ˜357 Ma (coeval with Devonian basin formation). Altogether, our data suggest that rather than being active continuously for 80 million years, the FRD consisted of multiple splays that were active for shorter intervals over discrete time periods separated by as much as 60 million years. Finally, our data provide evidence that young extensional deformation associated with postorogenic collapse in East Greenland was not restricted to the formation of sedimentary basins in the far eastern part of the orogen, but also resulted in deformation of the Archean-Paleozoic crystalline basement.

Determination of Coronal Magnetic Fields from Vector Magnetograms

NASA Technical Reports Server (NTRS)

Mikic, Zoran

1997-01-01

During the course of the present contract we developed an 'evolutionary technique' for the determination of force-free coronal magnetic fields from vector magnetograph observations. The method can successfully generate nonlinear force- free fields (with non-constant-a) that match vector magnetograms. We demonstrated that it is possible to determine coronal magnetic fields from photospheric measurements, and we applied it to vector magnetograms of active regions. We have also studied theoretical models of coronal fields that lead to disruptions. Specifically, we have demonstrated that the determination of force-free fields from exact boundary data is a well-posed mathematical problem, by verifying that the computed coronal field agrees with an analytic force-free field when boundary data for the analytic field are used; demonstrated that it is possible to determine active-region coronal magnetic fields from photospheric measurements, by computing the coronal field above active region 5747 on 20 October 1989, AR6919 on 15 November 1991, and AR7260 on 18 August 1992, from data taken with the Stokes Polarimeter at Mees Solar Observatory, University of Hawaii; started to analyze active region 7201 on 19 June 1992 using measurements made with the Advanced Stokes Polarimeter at NSO/Sac Peak; investigated the effects of imperfections in the photospheric data on the computed coronal magnetic field; documented the coronal field structure of AR5747 and compared it to the morphology of footpoint emission in a flare, showing that the 'high- pressure' H-alpha footpoints are connected by coronal field lines; shown that the variation of magnetic field strength along current-carrying field lines is significantly different from the variation in a potential field, and that the resulting near-constant area of elementary flux tubes is consistent with observations; begun to develop realistic models of coronal fields which can be used to study flare trigger mechanisms; demonstrated that magnetic nonequilibrium can disrupt sheared coronal arcades, and that helmet streamers can disrupt, leading to coronal mass ejections. Our model has significantly extended the realism with which the coronal magnetic field can be inferred from actual observations. In a subsequent contract awarded by NASA, we have continued to apply and improve the evolutionary technique, to study the physical properties of active regions, and to develop theoretical models of magnetic fields.

75 FR 29655 - Amendment of Class E Airspace; Batesville, AR

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

...-1177; Airspace Docket No. 09-ASW-34] Amendment of Class E Airspace; Batesville, AR AGENCY: Federal... Batesville, AR. Decommissioning of the Independence County non-directional beacon (NDB) at Batesville Regional Airport, Batesville, AR, has made this action necessary to enhance the safety and management of...

Comparison of Functional Network Connectivity for Passive-Listening and Active-Response Narrative Comprehension in Adolescents

PubMed Central

Holland, Scott K.

2014-01-01

Abstract Comprehension of narrative stories plays an important role in the development of language skills. In this study, we compared brain activity elicited by a passive-listening version and an active-response (AR) version of a narrative comprehension task by using independent component (IC) analysis on functional magnetic resonance imaging data from 21 adolescents (ages 14–18 years). Furthermore, we explored differences in functional network connectivity engaged by two versions of the task and investigated the relationship between the online response time and the strength of connectivity between each pair of ICs. Despite similar brain region involvements in auditory, temporoparietal, and frontoparietal language networks for both versions, the AR version engages some additional network elements including the left dorsolateral prefrontal, anterior cingulate, and sensorimotor networks. These additional involvements are likely associated with working memory and maintenance of attention, which can be attributed to the differences in cognitive strategic aspects of the two versions. We found significant positive correlation between the online response time and the strength of connectivity between an IC in left inferior frontal region and an IC in sensorimotor region. An explanation for this finding is that longer reaction time indicates stronger connection between the frontal and sensorimotor networks caused by increased activation in adolescents who require more effort to complete the task. PMID:24689887

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

Domain size sensitivities of landfalling eastern Pacific atmospheric rivers

NASA Astrophysics Data System (ADS)

McClenny, E. E.; Ullrich, P. A.; Grotjahn, R.; Guan, B.; Waliser, D. E.

2017-12-01

Atmospheric rivers (ARs) concentrate a majority of mid-latitude latent heat transport into narrow bands. ARs making landfall along the North American coast typically originate in the waters surrounding Hawaii. We explore here the effects of explicitly simulating this "genesis region" on AR characteristics. We do this using two models and three domains centered on the North American coast. The Weather Research and Forecast (WRF) model, forced by National Center for Environmental Prediction Final Reanalysis data, provides a representative regional model. The simulation domains include: 1. Just off the coastline (100-130W), 2. The coastline to the Pacific just east of Hawaii (100-155W), and 3. The coastline to the Pacific west of Hawaii (100-180W). The Variable Resolution Community Earth System Model simulates ARs while preserving global interactions. In this global model, "domain" refers to the mesh refinement region, each of which corresponds to one of the three previously described WRF domains. We compare ARs from the wet season (October-April) for water years 2009-2017 in the test models against those found in the Modern Era Retrospective Reanalysis 2 (MERRA2). We objectively detect events with the global AR detection algorithm introduced in Guan and Waliser (2015). Comparisons between all model configurations and the reference MERRA2 data will be assessed by characteristics including landfall location (meridional distributions, including quartile ranges and standard deviations of landfalls across the coast), as well as vapor flux and precipitation (in terms of both the contribution of ARs to the larger regional climatology and any differences in the intensity of individual AR events across runs).

Pre-Himalayan tectono-magmatic imprints in the Darjeeling-Sikkim Himalaya (DSH) constrained by 40Ar/39Ar dating of muscovite

NASA Astrophysics Data System (ADS)

Acharyya, Subhrangsu K.; Ghosh, Subhajit; Mandal, Nibir; Bose, Santanu; Pande, Kanchan

2017-09-01

The Lower Lesser Himalayan Sequence (L-LHS) in Darjeeling-Sikkim Himalaya (DSH) displays intensely deformed, low-grade meta-sedimentary rocks, frequently intervened by granite intrusives of varied scales. The principal motivation of our present study is to constrain the timing of this granitic event. Using 40Ar/39Ar geochronology, we dated muscovite from pegmatites emplaced along the earliest fabric in the low grade Daling phyllite, and obtained ∼1850 Ma Ar-Ar muscovite cooling age, which is broadly coeval with crystallization ages of Lingtse granite protolith (e.g., 1800-1850 Ma U-Pb zircon ages) reported from the L-LHS. We present here field observations to show the imprints (tectonic fabrics) of multiple ductile deformation episodes in the LHS terrain. The earliest penetrative fabric, axial planar to N-S trending reclined folds, suggest a regional tectonic event in the DSH prior to the active phase of Indo-Asia collision. Based on the age of granitic bodies and their structural correlation with the earliest fabric, we propose that the L-LHS as a distinct convergent tectono-magmatic belt, delineating the northern margin of Indian craton in the framework of the ∼1850 Ma Columbia supercontinent assembly.

C5aR expression in a novel GFP reporter gene knock-in mouse: implications for the mechanism of action of C5aR signaling in T cell immunity1

PubMed Central

Dunkelberger, Jason; Zhou, Lin; Miwa, Takashi; Song, Wen-Chao

2012-01-01

C5aR is a G protein-coupled receptor for the anaphylatoxin C5a and mediates many pro-inflammatory reactions. C5aR signaling has also been shown to regulate T cell immunity, but its sites and mechanism of action in this process remains uncertain. Here, we created a green fluorescence protein (GFP) knock-in mouse and used GFP as a surrogate marker to examine C5aR expression. GFP was knocked into the 3′-untranslated region (3′-UTR) of C5aR by gene targeting. We show that GFP is expressed highly on Gr-1+CD11b+ cells in the blood, spleen and bone marrow (BM), and moderately on CD11b+F4/80+ circulating leukocytes and elicited peritoneal macrophages. No GFP is detected on resting or activated T lymphocytes, nor on splenic myeloid or plasmacytoid dendritic cells. In contrast, 5–20% cultured BM-derived dendritic cells expressed GFP. Interestingly, GFP knock-in prevented cell surface but not intracellular C5aR expression. We conclude that C5aR is unlikely to play an intrinsic role on murine T cells and primary DCs. Instead, its effect on T cell immunity in vivo may involve CD11b+F4/80+ or other C5aR-expressing leukocytes. Further, our data reveal a surprising role of the 3′UTR of C5aR mRNA in regulating C5aR protein targeting to the plasma membrane. PMID:22430734

Assessment of a recombinant androgen receptor binding assay: initial steps towards validation.

PubMed

Freyberger, Alexius; Weimer, Marc; Tran, Hoai-Son; Ahr, Hans-Jürgen

2010-08-01

Despite more than a decade of research in the field of endocrine active compounds with affinity for the androgen receptor (AR), still no validated recombinant AR binding assay is available, although recombinant AR can be obtained from several sources. With funding from the European Union (EU)-sponsored 6th framework project, ReProTect, we developed a model protocol for such an assay based on a simple AR binding assay recently developed at our institution. Important features of the protocol were the use of a rat recombinant fusion protein to thioredoxin containing both the hinge region and ligand binding domain (LBD) of the rat AR (which is identical to the human AR-LBD) and performance in a 96-well plate format. Besides two reference compounds [dihydrotestosterone (DHT), androstenedione] ten test compounds with different affinities for the AR [levonorgestrel, progesterone, prochloraz, 17alpha-methyltestosterone, flutamide, norethynodrel, o,p'-DDT, dibutylphthalate, vinclozolin, linuron] were used to explore the performance of the assay. At least three independent experiments per compound were performed. The AR binding properties of reference and test compounds were well detected, in terms of the relative ranking of binding affinities, there was good agreement with published data obtained from experiments using recombinant AR preparations. Irrespective of the chemical nature of the compound, individual IC(50)-values for a given compound varied by not more than a factor of 2.6. Our data demonstrate that the assay reliably ranked compounds with strong, weak, and no/marginal affinity for the AR with high accuracy. It avoids the manipulation and use of animals, as a recombinant protein is used and thus contributes to the 3R concept. On the whole, this assay is a promising candidate for further validation. Copyright 2009 Elsevier Inc. All rights reserved.

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

Property Analysis of the Real-Time Uncalibrated Phase Delay Product Generated by Regional Reference Stations and Its Influence on Precise Point Positioning Ambiguity Resolution

PubMed Central

Zhang, Yong; Wang, Qing; Jiang, Xinyuan

2017-01-01

The real-time estimation of the wide-lane and narrow-lane Uncalibrated Phase Delay (UPD) of satellites is realized by real-time data received from regional reference station networks; The properties of the real-time UPD product and its influence on real-time precise point positioning ambiguity resolution (RTPPP-AR) are experimentally analyzed according to real-time data obtained from the regional Continuously Operating Reference Stations (CORS) network located in Tianjin, Shanghai, Hong Kong, etc. The results show that the real-time wide-lane and narrow-lane UPD products differ significantly from each other in time-domain characteristics; the wide-lane UPDs have daily stability, with a change rate of less than 0.1 cycle/day, while the narrow-lane UPDs have short-term stability, with significant change in one day. The UPD products generated by different regional networks have obvious spatial characteristics, thus significantly influencing RTPPP-AR: the adoption of real-time UPD products employing the sparse stations in the regional network for estimation is favorable for improving the regional RTPPP-AR up to 99%; the real-time UPD products of different regional networks slightly influence PPP-AR positioning accuracy. After ambiguities are successfully fixed, the real-time dynamic RTPPP-AR positioning accuracy is better than 3 cm in the plane and 8 cm in the upward direction. PMID:28534844

Property Analysis of the Real-Time Uncalibrated Phase Delay Product Generated by Regional Reference Stations and Its Influence on Precise Point Positioning Ambiguity Resolution.

PubMed

Zhang, Yong; Wang, Qing; Jiang, Xinyuan

2017-05-19

The real-time estimation of the wide-lane and narrow-lane Uncalibrated Phase Delay (UPD) of satellites is realized by real-time data received from regional reference station networks; The properties of the real-time UPD product and its influence on real-time precise point positioning ambiguity resolution (RTPPP-AR) are experimentally analyzed according to real-time data obtained from the regional Continuously Operating Reference Stations (CORS) network located in Tianjin, Shanghai, Hong Kong, etc. The results show that the real-time wide-lane and narrow-lane UPD products differ significantly from each other in time-domain characteristics; the wide-lane UPDs have daily stability, with a change rate of less than 0.1 cycle/day, while the narrow-lane UPDs have short-term stability, with significant change in one day. The UPD products generated by different regional networks have obvious spatial characteristics, thus significantly influencing RTPPP-AR: the adoption of real-time UPD products employing the sparse stations in the regional network for estimation is favorable for improving the regional RTPPP-AR up to 99%; the real-time UPD products of different regional networks slightly influence PPP-AR positioning accuracy. After ambiguities are successfully fixed, the real-time dynamic RTPPP-AR positioning accuracy is better than 3 cm in the plane and 8 cm in the upward direction.

Containing Unusual Resistance

MedlinePlus

... by germs resistant to antibiotics. While antibiotic resistance (AR) threats vary nationwide, AR has been found in every state. And unusual ... Coordinate with affected health care facilities, the new AR Lab Network regional labs, and CDC for every ...

Unmet Primary Physicians' Needs for Allergic Rhinitis Care in Korea.

PubMed

Yang, Hyeon Jong; Kim, Young Hyo; Lee, Bora; Kong, Do Youn; Kim, Dong Kyu; Kim, Mi Ae; Kim, Bong Seong; Kim, Won Young; Kim, Jeong Hee; Park, Yang; Park, So Yeon; Bae, Woo Yong; Song, Keejae; Yang, Min Suk; Lee, Sang Min; Lee, Young Mok; Lee, Hyun Jong; Cho, Jae Hong; Jee, Hye Mi; Choi, Jeong Hee; Yoo, Young; Koh, Young Il

2017-05-01

Allergic rhinitis (AR) is one of the most common chronic allergic respiratory diseases worldwide. Various practical guidelines for AR have been developed and updated to improve the care of AR patients; however, up to 40% patients remain symptomatic. The unmet need for AR care is one of the greatest public health problems in the world. The gaps between guideline and real-world practice, and differences according to the region, culture, and medical environments may be the causes of unmet needs for AR care. Because there is no evidence-based AR practical guideline reflecting the Korean particularity, various needs are increasing. The purpose of the study was to evaluate whether existing guidelines are sufficient for AR patient management in real practice and whether development of regional guidelines to reflect regional differences is needed in Korea. A total of 99 primary physicians comprising internists, pediatricians, and otolaryngologists (n=33 for each) were surveyed by a questionnaire relating to unmet needs for AR care between June 2 and June 16 of 2014. Among 39 question items, participants strongly agreed on 15 items that existing guidelines were highly insufficient and needed new guidelines. However, there was some disagreement according to specialties for another 24 items. In conclusion, the survey results demonstrated that many physicians did not agree with the current AR guideline, and a new guideline reflecting Korean particularity was needed. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.

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

Natural ³⁷Ar concentrations in soil air: implications for monitoring underground nuclear explosions.

PubMed

Riedmann, Robin A; Purtschert, Roland

2011-10-15

For on-site inspections (OSI) under the Comprehensive Nuclear-Test-Ban Treaty (CTBT) measurement of the noble gas ³⁷Ar is considered an important technique. ³⁷Ar is produced underground by neutron activation of Calcium by the reaction ⁴⁰Ca(n,α)³⁷Ar. The naturally occurring equilibrium ³⁷Ar concentration balance in soil air is a function of an exponentially decreasing production rate from cosmic ray neutrons with increasing soil depth, diffusive transport in the soil air, and radioactive decay (T(1/2): 35 days). In this paper for the first time, measurements of natural ³⁷Ar activities in soil air are presented. The highest activities of ~100 mBq m⁻³ air are 2 orders of magnitude larger than in the atmosphere and are found in 1.5-2.5 m depth. At depths > 8 m ³⁷Ar activities are < 20 mBq m⁻³ air. After identifying the main ³⁷Ar production and gas transport factors the expected global activity range distribution of ³⁷Ar in shallow subsoil (0.7 m below the surface) was estimated. In high altitude soils, with large amounts of Calcium and with low gas permeability, ³⁷Ar activities may reach values up to 1 Bq m⁻³.

An overview of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx)

NASA Astrophysics Data System (ADS)

Dulac, François

2014-05-01

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr) is a French initiative of the MISTRALS meta-programme (Mediterranean Integrated Studies at Regional And Locals Scales, http://www.mistrals-home.org). It federates a great number of national and international cooperative research actions aiming at a scientific assessment of the present and future state of the atmospheric environment in the Mediterranean Basin, and of its impacts on the regional climate, air quality, and marine biogeochemistry. The target is short-lived particulate and gaseous tropospheric trace species which are the cause of poor air quality events, have two-way interactions with climate, or impact the marine biogeochemistry, in a context of strong regional anthropogenic and climatic pressures. The six ChArMEx work packages include Emissions, Chemical processes and ageing, Transport processes and air quality, Aerosol-radiation-climate interactions, Deposition, and Present and future variability and trends. For several years, efforts have been deployed in several countries to develop (i) a network of relevant stations for atmospheric chemistry at background sites on islands and continental coasts around the basin and (ii) several intensive field campaigns including the operation of surface supersites and various instrumented mobile platforms (large and ultra-light aircraft, sounding and drifting balloons, ZeroCO2 sailboat). This presentation is an attempt to provide an overview of the various experimental, remote sensing and modelling efforts produced and to highlight major findings, by referencing more detailed ChArMEx presentations given in this conference and recently published or submitted papers. During the first phase of the project experimental efforts have been mainly concentrated on the western basin. Plans for the 2nd phase of ChArMEx, more dedicated towards the eastern basin, will also be given. In particular we plan to develop monitoring activities at Cyprus and put more emphasis (i) on aerosol-cloud interactions in cooperation with the FP7/Environment project BACCHUS, (ii) the budget and transport of anthropogenic emissions from megacities, and (iii) processes at the air-sea interface with a proposal for a 1-month oceanographic cruise during a period of dust deposition events, joint with the biogeochemistry component of MISTRALS (project MERMEX: the Marine Ecosystem Response Mediterranean Experiment). Acknowledgements: ChArMEx activities involve about 50 institutes. FD expresses his gratitude to every contributing scientist. ChArMEx is supported by too many agencies for listing them all here. The main overall effort is from France, with ADEME, ANR, CNES, CNRS-INSU, the Collectivité Territoriale de Corse (incl. EU-FEDER funds), Météo-France, CEA and Ecole des Mines de Douai as the main funding agencies.

Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics.

PubMed

Larenas-Linnemann, Désirée; Michels, Alexandra; Dinger, Hanna; Shah-Hosseini, Kijawasch; Mösges, Ralph; Arias-Cruz, Alfredo; Ambriz-Moreno, Marichuy; Barajas, Martín Bedolla; Javier, Ruth Cerino; de la Luz Cid Del Prado, María; Moreno, Manuel Alejandro Cruz; Almaráz, Roberto García; García-Cobas, Cecilia Y; Garcia Imperial, Daniel A; Muñoz, Rosa Garcia; Hernández-Colín, Dante; Linares-Zapien, Francisco J; Luna-Pech, Jorge A; Matta-Campos, Juan J; Jiménez, Norma Martinez; Medina-Ávalos, Miguel A; Hernández, Alejandra Medina; Maldonado, Alberto Monteverde; López, Doris N; Pizano Nazara, Luis J; Sanchez, Emmanuel Ramirez; Ramos-López, José D; Rodríguez-Pérez, Noel; Rodríguez-Ortiz, Pablo G

2014-01-01

Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age. In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes. 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005). In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens -some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries.

Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics

PubMed Central

2014-01-01

Background Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age. Methods In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes. Results 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005). Conclusions In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens –some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries. PMID:24976949

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.

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

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.

THE ORIGIN OF NET ELECTRIC CURRENTS IN SOLAR ACTIVE REGIONS

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

Dalmasse, K.; Aulanier, G.; Démoulin, P.

There is a recurring question in solar physics regarding whether or not electric currents are neutralized in active regions (ARs). This question was recently revisited using three-dimensional (3D) magnetohydrodynamic (MHD) numerical simulations of magnetic flux emergence into the solar atmosphere. Such simulations showed that flux emergence can generate a substantial net current in ARs. Other sources of AR currents are photospheric horizontal flows. Our aim is to determine the conditions for the occurrence of net versus neutralized currents with this second mechanism. Using 3D MHD simulations, we systematically impose line-tied, quasi-static, photospheric twisting and shearing motions to a bipolar potentialmore » magnetic field. We find that such flows: (1) produce both direct and return currents, (2) induce very weak compression currents—not observed in 2.5D—in the ambient field present in the close vicinity of the current-carrying field, and (3) can generate force-free magnetic fields with a net current. We demonstrate that neutralized currents are in general produced only in the absence of magnetic shear at the photospheric polarity inversion line—a special condition that is rarely observed. We conclude that  photospheric flows, as magnetic flux emergence, can build up net currents in the solar atmosphere, in agreement with recent observations. These results thus provide support for eruption models based on pre-eruption magnetic fields that possess a net coronal current.« less

Using observations of slipping velocities to test the hypothesis that reconnection heats the active region corona

NASA Astrophysics Data System (ADS)

Yang, Kai; Longcope, Dana; Guo, Yang; Ding, Mingde

2017-08-01

Numerous proposed coronal heating mechanisms have invoked magnetic reconnection in some role. Testing such a mechanism requires a method of measuring magnetic reconnection coupled with a prediction of the heat delivered by reconnection at the observed rate. In the absence of coronal reconnection, field line footpoints move at the same velocity as the plasma they find themselves in. The rate of coronal reconnection is therefore related to any discrepancy observed between footpoint motion and that of the local plasma — so-called slipping motion. We propose a novel method to measure this velocity discrepancy by combining a sequence of non-linear force-free field extrapolations with maps of photospheric velocity. We obtain both from a sequence of vector magnetograms of an active region (AR). We then propose a method of computing the coronal heating produced under the assumption the observed slipping velocity was due entirely to coronal reconnection. This heating rate is used to predict density and temperature at points along an equilibrium loop. This, in turn, is used to synthesize emission in EUV and SXR bands. We perform this analysis using a sequence of HMI vector magnetograms of a particular AR and compare synthesized images to observations of the same AR made by SDO. We also compare differential emission measure inferred from those observations to that of the modeled corona.

Plasma flows and magnetic field interplay during the formation of a pore

NASA Astrophysics Data System (ADS)

Ermolli, I.; Cristaldi, A.; Giorgi, F.; Giannattasio, F.; Stangalini, M.; Romano, P.; Tritschler, A.; Zuccarello, F.

2017-04-01

Aims: Recent simulations of solar magneto-convection have offered new levels of understanding of the interplay between plasma motions and magnetic fields in evolving active regions. We aim at verifying some aspects of the formation of magnetic regions derived from recent numerical studies in observational data. Methods: We studied the formation of a pore in the active region (AR) NOAA 11462. We analysed data obtained with the Interferometric Bidimensional Spectrometer (IBIS) at the Dunn Solar Telescope on April 17, 2012, consisting of full Stokes measurements of the Fe I 617.3 nm lines. Furthermore, we analysed SDO/HMI observations in the continuum and vector magnetograms derived from the Fe I 617.3 nm line data taken from April 15 to 19, 2012. We estimated the magnetic field strength and vector components and the line-of-sight (LOS) and horizontal motions in the photospheric region hosting the pore formation. We discuss our results in light of other observational studies and recent advances of numerical simulations. Results: The pore formation occurs in less than 1 h in the leading region of the AR. We observe that the evolution of the flux patch in the leading part of the AR is faster (<12 h) than the evolution (20-30 h) of the more diffuse and smaller scale flux patches in the trailing region. During the pore formation, the ratio between magnetic and dark area decreases from 5 to 2. We observe strong downflows at the forming pore boundary and diverging proper motions of plasma in the vicinity of the evolving feature that are directed towards the forming pore. The average values and trends of the various quantities estimated in the AR are in agreement with results of former observational studies of steady pores and with their modelled counterparts, as seen in recent numerical simulations of a rising-tube process. The agreement with the outcomes of the numerical studies holds for both the signatures of the flux emergence process (e.g. appearance of small-scale mixed polarity patterns and elongated granules) and the evolution of the region. The processes driving the formation of the pore are identified with the emergence of a magnetic flux concentration and the subsequent reorganization of the emerged flux, by the combined effect of velocity and magnetic field, in and around the evolving structure. Movies associated to Figs. 1 and 4 are available at http://www.aanda.org

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.

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.

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.

Multi-spacecraft Observations of the Coronal and Interplanetary Evolution of a Solar Eruption Associated with Two Active Regions

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

Hu, Huidong; Liu, Ying D.; Wang, Rui

We investigate the coronal and interplanetary evolution of a coronal mass ejection (CME) launched on 2010 September 4 from a source region linking two active regions (ARs), 11101 and 11103, using extreme ultraviolet imaging, magnetogram, white-light, and in situ observations from SDO , STEREO , SOHO , VEX , and Wind . A potential-field source-surface model is employed to examine the configuration of the coronal magnetic field surrounding the source region. The graduated cylindrical shell model and a triangulation method are applied to determine the kinematics of the CME in the corona and interplanetary space. From the remote sensing andmore » in situ observations, we obtain some key results: (1) the CME was deflected in both the eastward and southward directions in the low corona by the magnetic pressure from the two ARs, and possibly interacted with another ejection, which caused that the CME arrived at VEX that was longitudinally distant from the source region; (2) although VEX was closer to the Sun, the observed and derived CME arrival times at VEX are not earlier than those at Wind , which suggests the importance of determining both the frontal shape and propagation direction of the CME in interplanetary space; and (3) the ICME was compressed in the radial direction while the longitudinal transverse size was extended.« less

NF-κB and androgen receptor variant expression correlate with human BPH progression.

PubMed

Austin, David C; Strand, Douglas W; Love, Harold L; Franco, Omar E; Jang, Alex; Grabowska, Magdalena M; Miller, Nicole L; Hameed, Omar; Clark, Peter E; Fowke, Jay H; Matusik, Robert J; Jin, Ren J; Hayward, Simon W

2016-04-01

Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy. © 2015 Wiley Periodicals, Inc.

Brittle deformation during Alpine basal accretion and the origin of seismicity nests above the subduction interface

NASA Astrophysics Data System (ADS)

Menant, Armel; Angiboust, Samuel; Monié, Patrick; Oncken, Onno; Guigner, Jean-Michel

2018-04-01

Geophysical observations on active subduction zones have evidenced high seismicity clusters at 20-40 km depth in the fore-arc region whose origin remains controversial. We report here field observations of pervasive pseudotachylyte networks (interpreted as evidence for paleo-seismicity) in the now-exhumed Valpelline continental unit (Dent Blanche complex, NW. Alps, Italy), a tectonic sliver accreted to the upper plate at c. 30 km depth during the Paleocene Alpine subduction. Pre-alpine granulite-facies paragneiss from the core of the Valpelline unit are crosscut by widespread, mm to cm-thick pseudotachylyte veins. Co-seismic heating and subsequent cooling led to the formation of Ti-rich garnet rims, ilmenite needles, Ca-rich plagioclase, biotite microliths and hercynite micro-crystals. 39Ar-40Ar dating yields a 51-54 Ma age range for these veins, thus suggesting that frictional melting events occurred near peak burial conditions while the Valpelline unit was already inserted inside the duplex structure. In contrast, the base of the Valpelline unit underwent synchronous ductile and brittle, seismic deformation under water-bearing conditions followed by a re-equilibration at c. 40 Ma (39Ar-40Ar on retrograded pseudotachylyte veins) during exhumation-related deformation. Calculated rheological profiles suggest that pseudotachylyte veins from the dry core of the granulite unit record upper plate micro-seismicity (Mw 2-3) formed under very high differential stresses (>500 MPa) while the sheared base of the unit underwent repeated brittle-ductile deformation at much lower differential stresses (<40 MPa) in a fluid-saturated environment. These results demonstrate that some of the seismicity clusters nested along and above the plate interface may reflect the presence of stiff tectonic slivers rheologically analogous to the Valpelline unit acting as repeatedly breaking asperities in the basal accretion region of active subduction zones.

Functional analysis of the sea urchin-derived arylsulfatase (Ars)-element in mammalian cells.

PubMed

Watanabe, Satoshi; Watanabe, Sachiko; Sakamoto, Naoaki; Sato, Masahiro; Akasaka, Koji

2006-09-01

An insulator is a DNA sequence that has both enhancer-blocking activity, through its ability to modify the influence of neighboring cis-acting elements, and a barrier function that protects a transgene from being silenced by surrounding chromatin. Previously, we isolated and characterized a 582-bp-long element from the sea urchin arylsulfatase gene (Ars). This Ars-element was effective in sea urchin and Drosophila embryos and in plant cells. To investigate Ars-element activity in mammalian cells, we placed the element between the cytomegalovirus enhancer and a luciferase (luc) expression cassette. In contrast to controls lacking the Ars-element, NIH3T3 and 293T cells transfected with the element-containing construct displayed reduced luciferase activities. The Ars-element therefore acts as an enhancer-blocking element in mammalian cells. We assessed the barrier activity of the Ars-element using vectors in which a luc expression cassette was placed between two elements. Transfection experiments demonstrated that luc activity in these vectors was approximately ten-fold higher than in vectors lacking elements. Luc activities were well maintained even after 12 weeks in culture. Our observations demonstrate that the Ars-element has also a barrier activity. These results indicated that the Ars-element act as an insulator in mammalian cells.

Modelling and stability analysis of switching impulsive power systems with multiple equilibria

NASA Astrophysics Data System (ADS)

Zhu, Liying; Qiu, Jianbin; Chadli, Mohammed

2017-12-01

This paper tries to model power systems accompanied with a series of faults in the form of switched impulsive Hamiltonian systems (SIHSs) with multiple equilibria (ME) and unstable subsystems (US), and then analyze long-term stability issues of the power systems from the viewpoint of mathematics. According to the complex phenomena of switching actions of stages and generators, impulses of state, and existence of multiple equilibria, this paper first introduces an SIHS with ME and US to formulate a switching impulsive power system composed of an active generator, a standby generator, and an infinite load. Then, based on special system structures, a unique compact region containing all ME is determined, and novel stability concepts of region stability (RS), asymptotic region stability (ARS), and exponential region stability (ERS) are defined for such SIHS with respect to the region. Third, based on the introduced stability concepts, this paper proposes a necessary and sufficient condition of RS and ARS and a sufficient condition of ERS for the power system with respect to the region via the maximum energy function method. Finally, numerical simulations are carried out for a power system to show the effectiveness and practicality of the obained novel results.

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

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

The Celecoxib Derivative AR-12 Has Broad-Spectrum Antifungal Activity In Vitro and Improves the Activity of Fluconazole in a Murine Model of Cryptococcosis

PubMed Central

Koselny, Kristy; Green, Julianne; DiDone, Louis; Halterman, Justin P.; Fothergill, Annette W.; Wiederhold, Nathan P.; Patterson, Thomas F.; Cushion, Melanie T.; Rappelye, Chad; Wellington, Melanie

2016-01-01

Only one new class of antifungal drugs has been introduced into clinical practice in the last 30 years, and thus the identification of small molecules with novel mechanisms of action is an important goal of current anti-infective research. Here, we describe the characterization of the spectrum of in vitro activity and in vivo activity of AR-12, a celecoxib derivative which has been tested in a phase I clinical trial as an anticancer agent. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity, including activity against yeasts (e.g., Candida albicans, non-albicans Candida spp., Cryptococcus neoformans), molds (e.g., Fusarium, Mucor), and dimorphic fungi (Blastomyces, Histoplasma, and Coccidioides) with MICs of 2 to 4 μg/ml. AR-12 is also active against azole- and echinocandin-resistant Candida isolates, and subinhibitory AR-12 concentrations increase the susceptibility of fluconazole- and echinocandin-resistant Candida isolates. Finally, AR-12 also increases the activity of fluconazole in a murine model of cryptococcosis. Taken together, these data indicate that AR-12 represents a promising class of small molecules with broad-spectrum antifungal activity. PMID:27645246

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.

Suppression of heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep; Winebarger, Amy R.

2016-05-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the HMI onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral areas of the opposite polarity sunspots. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.We hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbra. Many transient, outstandingly bright, loops in the AIA 94 movie of the AR do have this expected rooting pattern. We will also present another example of AR in which we find a similar rooting pattern of coronal loops.

Do Atmospheric Rivers explain the extreme precipitation events over East Asia?

NASA Astrophysics Data System (ADS)

Dairaku, K.; Nayak, S.

2017-12-01

Extreme precipitation events are now of serious concern due to their damaging societal impacts over last few decades. Thus, climate indices are widely used to identify and quantify variability and changes in particular aspects of the climate system, especially when considering extremes. In our study, we focus on few climate indices of annual precipitation extremes for the period 1979-2013 over East Asia to discuss some straightforward information and interpretation of certain aspects of extreme precipitation events that occur over the region. To do so, we first discuss different percentiles of precipitation and maximum length of wet spell with different thresholds from a regional climate model (NRAMS) simulation at 20km. Results indicate that the 99 percentile of precipitation events correspond to about 80mm/d over few regions of East Asia during 1979-2013 and maximum length of wet spell with minimum 20mm precipitation corresponds to about 10days (Figure 1). We then linked the extreme precipitation events with the intense moisture transport events associated with atmospheric rivers (ARs). The ARs are identified by computing the vertically integrated horizontal water vapor transport (IVT) between 1000hpa and 300hpa with IVT ≥ 250 kg/m/s and 2000 km minimum long. With this threshold and condition (set by previous research), our results indicate that some extreme propitiation events are associated with some ARs over East Asia, while some events are not associated with any ARs. Similarly, some ARs are associated with some extreme precipitation events, while some ARs are not associated with any events. Since the ARs are sensitive to the threshold and condition depending on region, so we will analyze the characteristics of ARs (frequency, duration, and annual variability) with different thresholds and discuss their relationship with extreme precipitation events over East Asia.

Tyramide Signal Amplification Permits Immunohistochemical Analyses of Androgen Receptors in the Rat Prefrontal Cortex

PubMed Central

Low, Katelyn L.; Ma, Chunqi; Soma, Kiran K.

2017-01-01

Research on neural androgen receptors (ARs) has traditionally focused on brain regions that regulate reproductive and aggressive behaviors, such as the hypothalamus and amygdala. Although many cells in the prefrontal cortex (PFC) also express ARs, the number of ARs per cell appears to be much lower, and thus, AR immunostaining is often hard to detect and quantify in the PFC. Here, we demonstrate that biotin tyramide signal amplification (TSA) dramatically increases AR immunoreactivity in the rat brain, including critical regions of the PFC such as the medial PFC (mPFC) and orbitofrontal cortex (OFC). We show that TSA is useful for AR detection with both chromogenic and immunofluorescent immunohistochemistry. Double-labeling studies reveal that AR+ cells in the PFC and hippocampus are NeuN+ but not GFAP+ and thus primarily neuronal. Finally, in gonadally intact rats, more AR+ cells are present in the mPFC and OFC of males than of females. Future studies can use TSA to further examine AR immunoreactivity across ages, sexes, strains, and different procedures (e.g., fixation methods). In light of emerging evidence for the androgen regulation of executive function and working memory, these results may help understand the distribution and roles of ARs in the PFC. PMID:28438093

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.

Cooling, exhumation, and kinematics of the Kanchenjunga Himal, far east Nepal

NASA Astrophysics Data System (ADS)

Larson, Kyle P.; Camacho, Alfredo; Cottle, John M.; Coutand, Isabelle; Buckingham, Heather M.; Ambrose, Tyler K.; Rai, Santa Man

2017-06-01

New single crystal 40Ar/39Ar and apatite fission track ages from the Kanchenjunga region of far east Nepal yield insight into the timing of assembly of the Himalayan midcrust and the mechanisms that controlled its exhumation. The 40Ar/39Ar data are compared with new U(Th)/Pb zircon and monazite intrusive crystallization ages and existing metamorphic monazite ages from across the study area to test for internal consistency and potential excess Ar contributions. This new data set, which significantly enhances the density and spatial coverage available from the region, shows that inferred thrust-sense discontinuities within the now-exhumed former midcrustal rocks exposed therein must have ceased motion by 12 Ma. Furthermore, the spatial distribution of ages across the Kanchenjunga region, older ages ( 12-16 Ma) to the south and north and younger ages ( 8 Ma) in the middle portion of the transect, is compatible with simulations of tectonic-enhanced exhumation above a developing duplex system in nearby Bhutan.

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

Murabito, M.; Guglielmino, S. L.; Zuccarello, F.

We studied the formation of the first penumbral sector around a pore in the following polarity of the NOAA Active Region (AR) 11490. We used a high spatial, spectral, and temporal resolution data set acquired by the Interferometric BIdimensional Spectrometer operating at the NSO/Dunn Solar Telescope, as well as data taken by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory satellite. On the side toward the leading polarity, elongated granules in the photosphere and an arch filament system (AFS) in the chromosphere are present, while the magnetic field shows a sea-serpent configuration, indicating a region of magneticmore » flux emergence. We found that the formation of a stable penumbra in the following polarity of the AR begins in the area facing the opposite polarity located below the AFS in the flux emergence region, different from what was found by Schlichenmaier and colleagues. Moreover, during the formation of the first penumbral sector, the area characterized by magnetic flux density larger than 900 G and the area of the umbra increase.« less

Remote sensing-based characterization of rainfall during atmospheric rivers over the central United States

NASA Astrophysics Data System (ADS)

Nayak, Munir A.; Villarini, Gabriele

2018-01-01

Atmospheric rivers (ARs) play a central role in the hydrology and hydroclimatology of the central United States. More than 25% of the annual rainfall is associated with ARs over much of this region, with many large flood events tied to their occurrence. Despite the relevance of these storms for flood hydrology and water budget, the characteristics of rainfall associated with ARs over the central United has not been investigated thus far. This study fills this major scientific gap by describing the rainfall during ARs over the central United States using five remote sensing-based precipitation products over a 12-year study period. The products we consider are: Stage IV, Tropical Rainfall Measuring Mission - Multi-satellite Precipitation Analysis (TMPA, both real-time and research version); Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN); the CPC MORPHing Technique (CMORPH). As part of the study, we evaluate these products against a rain gauge-based dataset using both graphical- and metrics-based diagnostics. Based on our analyses, Stage IV is found to better reproduce the reference data. Hence, we use it for the characterization of rainfall in ARs. Most of the AR-rainfall is located in a narrow region within ∼150 km on both sides of the AR major axis. In this region, rainfall has a pronounced positive relationship with the magnitude of the water vapor transport. Moreover, we have also identified a consistent increase in rainfall intensity with duration (or persistence) of AR conditions. However, there is not a strong indication of diurnal variability in AR rainfall. These results can be directly used in developing flood protection strategies during ARs. Further, weather prediction agencies can benefit from the results of this study to achieve higher skill of resolving precipitation processes in their models.

Adenosine A2A Receptor Activation and Macrophage-mediated Experimental Glomerulonephritis

PubMed Central

Garcia, Gabriela E.; Truong, Luan D.; Li, Ping; Zhang, Ping; Du, Jie; Chen, Jiang-Fan; Feng, Lili

2010-01-01

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A2A adenosine receptors (A2AR) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine whether selective activation of A2AR will suppress inflammation in a rat model of glomerulonephritis. Activation of A2AR reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1α/CCL3, RANTES/CCL5, MIP-1β/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, IL-4 and IL-10, also increased. The mechanism for these anti-inflammatory responses to the A2AR agonist was suppression of macrophages function. A2AR expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A2AR agonist, and chemokines not expressed in macrophages did not respond to A2AR activation. Thus, activation of the A2AR on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A2AR activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A2AR could be developed into a novel treatment for glomerulonephritis and other macrophage-related inflammatory diseases. PMID:17898087

Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.

PubMed

Yin, Donghua; He, Yali; Perera, Minoli A; Hong, Seoung Soo; Marhefka, Craig; Stourman, Nina; Kirkovsky, Leonid; Miller, Duane D; Dalton, James T

2003-01-01

The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.

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

On the Factors Determining the Eruptive Character of Solar Flares

NASA Astrophysics Data System (ADS)

Baumgartner, Christian; Thalmann, Julia K.; Veronig, Astrid M.

2018-02-01

We investigated how the magnetic field in solar active regions (ARs) controls flare activity, i.e., whether a confined or eruptive flare occurs. We analyzed 44 flares of GOES class M5.0 and larger that occurred during 2011–2015. We used 3D potential magnetic field models to study their location (using the flare distance from the flux-weighted AR center d FC) and the strength of the magnetic field in the corona above (via decay index n and flux ratio). We also present a first systematic study of the orientation of the coronal magnetic field, using the orientation φ of the flare-relevant polarity inversion line as a measure. We analyzed all quantities with respect to the size of the underlying dipole field, characterized by the distance between the opposite-polarity centers, d PC. Flares originating from underneath the AR dipole (d FC/d PC < 0.5) tend to be eruptive if launched from compact ARs (d PC ≤ 60 Mm) and confined if launched from extended ARs. Flares ejected from the periphery of ARs (d FC/d PC > 0.5) are predominantly eruptive. In confined events, the flare-relevant field adjusts its orientation quickly to that of the underlying dipole with height (Δφ ≳ 40° until the apex of the dipole field), in contrast to eruptive events where it changes more slowly with height. The critical height for torus instability, h crit = h(n = 1.5), discriminates best between confined (h crit ≳ 40 Mm) and eruptive flares (h crit ≲ 40 Mm). It discriminates better than Δφ, implying that the decay of the confining field plays a stronger role than its orientation at different heights.

Simultaneous Observations of p-mode Light Walls and Magnetic Reconnection Ejections above Sunspot Light Bridges

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

Hou, Yijun; Zhang, Jun; Li, Ting

Recent high-resolution observations from the Interface Region Imaging Spectrograph reveal bright wall-shaped structures in active regions (ARs), especially above sunspot light bridges. Their most prominent feature is the bright oscillating front in the 1400/1330 Å channel. These structures are named light walls and are often interpreted to be driven by p-mode waves. Above the light bridge of AR 12222 on 2014 December 06, we observed intermittent ejections superimposed on an oscillating light wall in the 1400 Å passband. At the base location of each ejection, the emission enhancement was detected in the Solar Dynamics Observatory 1600 Å channel. Thus, wemore » suggest that in wall bases (light bridges), in addition to the leaked p-mode waves consistently driving the oscillating light wall, magnetic reconnection could happen intermittently at some locations and eject the heated plasma upward. Similarly, in the second event occurring in AR 12371 on 2015 June 16, a jet was simultaneously detected in addition to the light wall with a wave-shaped bright front above the light bridge. At the footpoint of this jet, lasting brightening was observed, implying magnetic reconnection at the base. We propose that in these events, two mechanisms, p-mode waves and magnetic reconnection, simultaneously play roles in the light bridge, and lead to the distinct kinetic features of the light walls and the ejection-like activities, respectively. To illustrate the two mechanisms and their resulting activities above light bridges, in this study we present a cartoon model.« less

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.

Alpha1-adrenergic receptor blockade in the VTA modulates fear memories and stress responses.

PubMed

Solecki, Wojciech B; Szklarczyk, Klaudia; Klasa, Adam; Pradel, Kamil; Dobrzański, Grzegorz; Przewłocki, Ryszard

2017-08-01

Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha 1 -adrenergic receptor (α 1 -AR) signaling in the VTA affects conditioned fear. The role of α 1 -AR was assessed using the micro-infusions into the VTA of the selective antagonists (0.1-1µg/0.5µl prazosin and 1µg/0.5µl terazosin) in acquisition and expression of fear memory. In addition, we performed control experiments with α 1 -AR blockade in the mammillary bodies (MB) - a brain region with α 1 -AR expression adjacent to the VTA. Intra-VTA but not intra-MB α 1 -AR blockade prevented formation and retrieval of fear memories. Importantly, local administration of α 1 -AR antagonists did not influence footshock sensitivity, locomotion or anxiety-like behaviors. Similarly, α 1 -AR blockade in the VTA had no effects on negative affect measured as number of 22kHz ultrasonic vocalizations during fear conditioning training. We propose that noradrenergic signaling in the VTA via α 1 -AR regulates formation and retrieval of fear memories but not other behavioral responses to stressful environmental stimuli. It enhances the encoding of environmental stimuli by the VTA to form and retrieve conditioned fear memories and to predict future behavioral outcomes. Our results provide novel insight into the role of the VTA α 1 -AR signaling in the regulation of stress responsiveness and fear memory. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Inferred flows of electric currents in solar active regions

NASA Technical Reports Server (NTRS)

Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.

1985-01-01

Techniques to identify sources of major current systems in active regions and their channels of flow are explored. Measured photospheric vector magnetic fields together with high resolution white light and H-alpha photographs provide the data base to derive the current systems in the photosphere and chromosphere of a solar active region. Simple mathematical constructions of active region fields and currents are used to interpret these data under the assumptions that the fields in the lower atmosphere (below 200 km) may not be force free but those in the chromosphere and higher are. The results obtained for the complex active region AR 2372 are: (1) Spots exhibiting significant spiral structure in the penumbral filaments were the source of vertical currents at the photospheric surface; (2) Magnetic neutral lines where the transverse magnetic field was strongly sheared were channels along which a strong current system flowed; (3) The inferred current systems produced a neutral sheet and oppositely-flowing currents in the area of the magnetic delta configuration that was the site of flaring.

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.

End-of-century projections of North American atmospheric river events in CMIP5 climate models

NASA Astrophysics Data System (ADS)

Warner, M.; Mass, C.; Salathe, E. P., Jr.

2013-12-01

Most extreme precipitation events that occur along the North American west coast are associated with narrow plumes of above-average water vapor concentration that stretch from the tropics or subtropics to the West Coast. These events generally occur during the wet season (October-March) and are referred to as atmospheric rivers (AR). ARs can cause major river management problems, damage from flooding or landslides, and loss of life. It is expected that anthropogenic global warming could lead to changes in the general circulation of the atmosphere, such as Hadley Cell expansion and jet stream and storm track shifts. Since AR events are associated with cyclonic activity that originates near and propagates along the jet stream, the jet stream configuration influences the frequency and location of AR landfall along the North American west coast. Therefore, it is probable that any changes in the general circulation of the atmosphere will result in changes in the frequency, orientation, and location of AR landfalls. Generally, along the West Coast, CMIP5 models predict increases in integrated water vapor and precipitation, and little change in low-level wind associated with AR events. In this study, CMIP5 RCP 8.5 climate models and high resolution regional climate models are used to analyze predicted changes in frequency and location of AR events impacting the West Coast from the contemporary period (1970-1999) to the end of this century (2070-2099).

MED1 mediates androgen receptor splice variant induced gene expression in the absence of ligand

PubMed Central

Liu, Gang; Sprenger, Cynthia; Wu, Pin-Jou; Sun, Shihua; Uo, Takuma; Haugk, Kathleen; Epilepsia, Kathryn Soriano; Plymate, Stephen

2015-01-01

The appearance of constitutively active androgen receptor splice variants (AR-Vs) has been proposed as one of the causes of castration-resistant prostate cancer (CRPC). However, the underlying mechanism of AR-Vs in CRPC transcriptional regulation has not been defined. A distinct transcriptome enriched with cell cycle genes, e.g. UBE2C, has been associated with AR-Vs, which indicates the possibility of an altered transcriptional mechanism when compared to full-length wild-type AR (ARfl). Importantly, a recent study reported the critical role of p-MED1 in enhancing UBE2C expression through a locus looping pattern, which only occurs in CRPC but not in androgen-dependent prostate cancer (ADPC). To investigate the potential correlation between AR-V and MED1, in the present study we performed protein co-immunoprecipitation, chromatin immunoprecipitation, and cell proliferation assays and found that MED1 is necessary for ARv567es induced UBE2C up-regulation and subsequent prostate cancer cell growth. Furthermore, p-MED1 is bound to ARv567es independent of full-length AR; p-MED1 has higher recruitment to UBE2C promoter and enhancer regions in the presence of ARv567es. Our data indicate that p-MED1 serves as a key mediator in ARv567es induced gene expression and suggests a mechanism by which AR-Vs promote the development and progression of CRPC. PMID:25481872

Translation, Cross-Cultural Adaptation, and Validation of the Activity Rating Scale for Disorders of the Knee.

PubMed

Flosadottir, Vala; Roos, Ewa M; Ageberg, Eva

2017-09-01

The Activity Rating Scale (ARS) for disorders of the knee evaluates the level of activity by the frequency of participation in 4 separate activities with high demands on knee function, with a score ranging from 0 (none) to 16 (pivoting activities 4 times/wk). To translate and cross-culturally adapt the ARS into Swedish and to assess measurement properties of the Swedish version of the ARS. Cohort study (diagnosis); Level of evidence, 2. The COSMIN guidelines were followed. Participants (N = 100 [55 women]; mean age, 27 years) who were undergoing rehabilitation for a knee injury completed the ARS twice for test-retest reliability. The Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale (TAS), and modernized Saltin-Grimby Physical Activity Level Scale (SGPALS) were administered at baseline to validate the ARS. Construct validity and responsiveness of the ARS were evaluated by testing predefined hypotheses regarding correlations between the ARS, KOOS, TAS, and SGPALS. The Cronbach alpha, intraclass correlation coefficients, absolute reliability, standard error of measurement, smallest detectable change, and Spearman rank-order correlation coefficients were calculated. The ARS showed good internal consistency (α ≈ 0.96), good test-retest reliability (intraclass correlation coefficient >0.9), and no systematic bias between measurements. The standard error of measurement was less than 2 points, and the smallest detectable change was less than 1 point at the group level and less than 5 points at the individual level. More than 75% of the hypotheses were confirmed, indicating good construct validity and good responsiveness of the ARS. The Swedish version of the ARS is valid, reliable, and responsive for evaluating the level of activity based on the frequency of participation in high-demand knee sports activities in young adults with a knee injury.

78 FR 52477 - Promulgation of State Implementation Plan Revisions; Revision to Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

...), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver, Colorado 80202-1129. Hand Delivery: Director, Air Program, Environmental Protection Agency (EPA), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver... Agency (EPA), Region 8, 1595 Wynkoop Street, Denver, Colorado 80202-1129. EPA requests that if at all...

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

A study of solar magnetic fields below the surface, at the surface, and in the solar atmosphere - understanding the cause of major solar activity

NASA Astrophysics Data System (ADS)

Chintzoglou, Georgios

2016-04-01

Magnetic fields govern all aspects of solar activity from the 11-year solar cycle to the most energetic events in the solar system, such as solar flares and Coronal Mass Ejections (CMEs). As seen on the surface of the sun, this activity emanates from localized concentrations of magnetic fields emerging sporadically from the solar interior. These locations are called solar Active Regions (ARs). However, the fundamental processes regarding the origin, emergence and evolution of solar magnetic fields as well as the generation of solar activity are largely unknown or remain controversial. In this dissertation, multiple important issues regarding solar magnetism and activities are addressed, based on advanced observations obtained by AIA and HMI instruments aboard the SDO spacecraft. First, this work investigates the formation of coronal magnetic flux ropes (MFRs), structures associated with major solar activity such as CMEs. In the past, several theories have been proposed to explain the cause of this major activity, which can be categorized in two contrasting groups (a) the MFR is formed in the eruption, and (b) the MFR pre-exists the eruption. This remains a topic of heated debate in modern solar physics. This dissertation provides a complete treatment of the role of MFRs from their genesis all the way to their eruption and even destruction. The study has uncovered the pre-existence of two weakly twisted MFRs, which formed during confined flaring 12 hours before their associated CMEs. Thus, it provides unambiguous evidence for MFRs truly existing before the CME eruptions, resolving the pre-existing MFR controversy. Second, this dissertation addresses the 3-D magnetic structure of complex emerging ARs. In ARs the photospheric fields might show all aspects of complexity, from simple bipolar regions to extremely complex multi-polar surface magnetic distributions. In this thesis, we introduce a novel technique to infer the subphotospheric configuration of emerging magnetic flux tubes while forming ARs on the surface. Using advanced 3D visualization tools and applying this technique on a complex flare and CME productive AR, we found that the magnetic flux tubes involved in forming the complex AR may originate from a single progenitor flux tube in the SCZ. The complexity can be explained as a result of vertical and horizontal bifurcations that occurred on the progenitor flux tube. Third, this dissertation proposes a new scenario on the origin of major solar activity. When more than one flux tubes are in close proximity to each other while they break through the photospheric surface, collision and shearing may occur as they emerge. Once this collisional shearing occurs between nonconjugated sunspots (opposite polarities not belonging to the same bipole), major solar activity is triggered. The collision and the shearing occur due to the natural separation of polarities in emerging bipoles. This is forcing changes in the connectivity close to the photosphere (up to a few local pressure scale heights above the surface) by means of photospheric reconnection and subsequent submergence of small bipoles at the collision interface (polarity inversion line; PIL). In this continuous collision, more poloidal flux is added to the system effectively creating an expanding MFR into the corona, explaining the observation of filament formation above the PIL together with flare activity and CMEs. Our results reject two popular scenarios on the possible cause of solar eruptions (1) eruption occurs due to shearing motion between conjugate polarities, and, (2) bodily emergence of an MFR.

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.

Efficient mining of association rules for the early diagnosis of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Chaves, R.; Górriz, J. M.; Ramírez, J.; Illán, I. A.; Salas-Gonzalez, D.; Gómez-Río, M.

2011-09-01

In this paper, a novel technique based on association rules (ARs) is presented in order to find relations among activated brain areas in single photon emission computed tomography (SPECT) imaging. In this sense, the aim of this work is to discover associations among attributes which characterize the perfusion patterns of normal subjects and to make use of them for the early diagnosis of Alzheimer's disease (AD). Firstly, voxel-as-feature-based activation estimation methods are used to find the tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs serve as input to secondly mine ARs with a minimum support and confidence among activation blocks by using a set of controls. In this context, support and confidence measures are related to the proportion of functional areas which are singularly and mutually activated across the brain. Finally, we perform image classification by comparing the number of ARs verified by each subject under test to a given threshold that depends on the number of previously mined rules. Several classification experiments were carried out in order to evaluate the proposed methods using a SPECT database that consists of 41 controls (NOR) and 56 AD patients labeled by trained physicians. The proposed methods were validated by means of the leave-one-out cross validation strategy, yielding up to 94.87% classification accuracy, thus outperforming recent developed methods for computer aided diagnosis of AD.

Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

PubMed

Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

2004-02-12

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators

PubMed Central

Marhefka, Craig A.; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T.; Miller, Duane D.

2007-01-01

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with Ki values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo. PMID:14761201

Behavioral Analysis of Genetically Modified Mice Indicates Essential Roles of Neurosteroidal Estrogen

PubMed Central

Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro

2011-01-01

Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807

Radioactivities in returned lunar materials.

NASA Technical Reports Server (NTRS)

Fireman, E. L.; D'Amico, J.; Defelice, J.; Spannagel, G.

1972-01-01

The difference between the Ar-37 activities from similar locations in the rocks 12002 and 15555 provides direct measures of the Ar-37 activities produced by the 2 November 1969 flare. Differences between the Ar-37 activities in 14321 and 15555 give Ar-37 activities produced by the 24 January 1971 flare. The intensities of the two flares were determined by making use of measured Ar-37 cross sections in simulated lunar material. The depth dependence of tritium in samples and its temperature-release pattern provides information about the sources of the tritium and about the intensity of solar flares integrated over the past 30 years.

Detailed Ar-Ar Geochronology of Volcanism at Minna Bluff, Antarctica: Two-Phased Growth and Influence on Ross Ice Shelf

NASA Astrophysics Data System (ADS)

Ross, J. I.; McIntosh, W. C.; Wilch, T. I.

2012-12-01

Minna Bluff has been a significant topographic barrier to the flow of the Ross Ice Shelf since the mid-Miocene. Detailed Ar-Ar analyses of kaersutite and sanidine phenocrysts, and groundmass concentrates from volcanic units indicate an overall west to east progression of volcanic activity. Eruptions of basaltic to intermediate lavas, domes, and scoria cones started at ~12 Ma in at what is now the eastern most point of Minna Bluff, "Minna Hook." Activity was centered in this area for ~4 Ma, constructing a pre-Minna Bluff island. Multiple glacial unconformities found at Minna Hook suggest repeated interaction with large warm-based, erosive ice sheets. Activity migrated westward from Minna Bluff Island at 7-8 Ma closing the gap created by the island and the mainland. Significant edifice construction continued until 4-5 Ma with sporadic and parasitic scoria cone eruptions, possibly associated with Mt. Discovery activity, continuing until 2 Ma. The orientations of Minna Bluff's two major axes are strongly controlled by regional tectonic features. Minna Bluff's E-W axis, McIntosh Cliffs, is sub-parallel to the Radial Lineament and the N-S axis, Minna Hook, appears as extension of faulting bounding the Terror Rift. The constructional evolution of the 70km long volcanic complex has an important role in interpreting the climate signals recovered by the ANDRILL Project. Minna Bluff influenced the material delivered to the AND-1B drill site (ANDRILL MIS 2006-2007) in three critical ways: 1) Minna Bluff diverted upstream material, 2) provided a pinning and stabilizing point for the Ross Ice Shelf, possible controlling the calving line prior to the emergence of Ross Island, and 3) was a significant source of fresh volcanic material throughout much of the period recovered by ANDRILL MIS. For example, a kaersutite-bearing clast recovered from 822.78 mbsf in AND-1B yielded an age of 8.53±0.51 Ma, and was likely derived from Minna Bluff. The results from this study can be incorporated into detailed glacier and ice-sheet models of the McMurdo Sound region, a critical area in the Ross Ice Sheet and global climate system.

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

RECURRENT EXPLOSIVE ERUPTIONS AND THE ''SIGMOID-TO-ARCADE'' TRANSFORMATION IN THE SUN DRIVEN BY DYNAMICAL MAGNETIC FLUX EMERGENCE

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

Archontis, V.; Hood, A. W.; Tsinganos, K., E-mail: va11@st-andrews.ac.uk

2014-05-10

We report on three-dimensional MHD simulations of recurrent mini coronal mass ejection (CME)-like eruptions in a small active region (AR), which is formed by the dynamical emergence of a twisted (not kink unstable) flux tube from the solar interior. The eruptions develop as a result of the repeated formation and expulsion of new flux ropes due to continuous emergence and reconnection of sheared field lines along the polarity inversion line of the AR. The acceleration of the eruptions is triggered by tether-cutting reconnection at the current sheet underneath the erupting field. We find that each explosive eruption is followed bymore » reformation of a sigmoidal structure and a subsequent ''sigmoid-to-flare arcade'' transformation in the AR. These results might have implications for recurrent CMEs and eruptive sigmoids/flares observations and theoretical studies.« less

Molecular interactions between fenoterol stereoisomers and derivatives and the β₂-adrenergic receptor binding site studied by docking and molecular dynamics simulations.

PubMed

Plazinska, Anita; Kolinski, Michal; Wainer, Irving W; Jozwiak, Krzysztof

2013-11-01

The β2 adrenergic receptor (β2-AR) has become a model system for studying the ligand recognition process and mechanism of the G protein coupled receptors activation. In the present study stereoisomers of fenoterol and some of its derivatives (N = 94 molecules) were used as molecular probes to identify differences in stereo-recognition interactions between β2-AR and structurally similar agonists. The present study aimed at determining the 3D molecular models of the fenoterol derivative-β2-AR complexes. Molecular models of β2-AR have been developed by using the crystal structure of the human β2-AR T4 lysozyme fusion protein with bound (S)-carazolol (PDB ID: 2RH1) and more recently reported structure of a nanobody-stabilized active state of the β2-AR with the bound full agonist BI-167107 (PDB ID: 3P0G). The docking procedure allowed us to study the similarities and differences in the recognition binding site(s) for tested ligands. The agonist molecules occupied the same binding region, between TM III, TM V, TM VI and TM VII. The residues identified by us during docking procedure (Ser203, Ser207, Asp113, Lys305, Asn312, Tyr308, Asp192) were experimentally indicated in functional and biophysical studies as being very important for the agonist-receptor interactions. Moreover, the additional space, an extension of the orthosteric pocket, was identified and described. Furthermore, the molecular dynamics simulations were used to study the molecular mechanism of interaction between ligands ((R,R')- and (S,S')-fenoterol) and β2-AR. Our research offers new insights into the ligand stereoselective interaction with one of the most important GPCR member. This study may also facilitate the design of improved selective medications, which can be used to treat, prevent and control heart failure symptoms.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors

PubMed Central

Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A.; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I.; McCormick, Peter J.; Maldonado, Rafael; Robledo, Patricia

2015-01-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties. PMID:26158621

Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes.

PubMed

Vardjan, Nina; Kreft, Marko; Zorec, Robert

2014-04-01

The morphology of astrocytes, likely regulated by cAMP, determines the structural association between astrocytes and the synapse, consequently modulating synaptic function. β-Adrenergic receptors (β-AR), which increase cytosolic cAMP concentration ([cAMP]i ), may affect cell morphology. However, the real-time dynamics of β-AR-mediated cAMP signaling in single live astrocytes and its effect on cell morphology have not been studied. We used the fluorescence resonance energy transfer (FRET)-based cAMP biosensor Epac1-camps to study time-dependent changes in [cAMP]i ; morphological changes in primary rat astrocytes were monitored by real-time confocal microscopy. Stimulation of β-AR by adrenaline, noradrenaline, and isoprenaline, a specific agonist of β-AR, rapidly increased [cAMP]i (∼15 s). The FRET signal response, mediated via β-AR, was faster than in the presence of forskolin (twofold) and dibutyryl-cAMP (>35-fold), which directly activate adenylyl cyclase and Epac1-camps, respectively, likely due to slow entry of these agents into the cytosol. Oscillations in [cAMP]i have not been recorded, indicating that cAMP-dependent processes operate in a slow time domain. Most Epac1-camps expressing astrocytes revealed a morphological change upon β-AR activation and attained a stellate morphology within 1 h. The morphological changes exhibited a bell-shaped dependency on [cAMP]i . The 5-10% decrease in cell cross-sectional area and the 30-50% increase in cell perimeter are likely due to withdrawal of the cytoplasm to the perinuclear region and the appearance of protrusions on the surface of astrocytes. Because astrocyte processes ensheath neurons, β-AR/cAMP-mediated morphological changes can modify the geometry of the extracellular space, affecting synaptic, neuronal, and astrocyte functions in health and disease. Copyright © 2014 Wiley Periodicals, Inc.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

PubMed

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Meteorological characteristics and overland precipitation impacts of atmospheric rivers affecting the West coast of North America based on eight years of SSM/I satellite observations

USGS Publications Warehouse

Neiman, P.J.; Ralph, F.M.; Wick, G.A.; Lundquist, J.D.; Dettinger, M.D.

2008-01-01

The pre-cold-frontal low-level jet within oceanic extratropical cyclones represents the lower-tropospheric component of a deeper corridor of concentrated water vapor transport in the cyclone warm sector. These corridors are referred to as atmospheric rivers (ARs) because they are narrow relative to their length scale and are responsible for most of the poleward water vapor transport at midlatitudes. This paper investigates landfalling ARs along adjacent north- and south-coast regions of western North America. Special Sensor Microwave Imager (SSM/ I) satellite observations of long, narrow plumes of enhanced integrated water vapor (IWV) were used to detect ARs just offshore over the eastern Pacific from 1997 to 2005. The north coast experienced 301 AR days, while the south coast had only 115. Most ARs occurred during the warm season in the north and cool season in the south, despite the fact that the cool season is climatologically wettest for both regions. Composite SSM/I IWV analyses showed landfalling wintertime ARs extending northeastward from the tropical eastern Pacific, whereas the summertime composites were zonally oriented and, thus, did not originate from this region of the tropics. Companion SSM/I composites of daily rainfall showed significant orographic enhancement during the landfall of winter (but not summer) ARs. The NCEP-NCAR global reanalysis dataset and regional precipitation networks were used to assess composite synoptic characteristics and overland impacts of landfalling ARs. The ARs possess strong vertically integrated horizontal water vapor fluxes that, on average, impinge on the West Coast in the pre-cold-frontal environment in winter and post-cold-frontal environment in summer. Even though the IWV in the ARs is greater in summer, the vapor flux is stronger in winter due to much stronger flows associated with more intense storms. The landfall of ARs in winter and north-coast summer coincides with anomalous warmth, a trough offshore, and ridging over the Intermountain West, whereas the south-coast summer ARs coincide with relatively cold conditions and a near-coast trough. ARs have a much more profound impact on near-coast precipitation in winter than summer, because the terrain-normal vapor flux is stronger and the air more nearly saturated in winter. During winter, ARs produce roughly twice as much precipitation as all storms. In addition, wintertime ARs with the largest SSM/I IWV are tied to more intense storms with stronger flows and vapor fluxes, and more precipitation. ARs generally increase snow water equivalent (SWE) in autumn/winter and decrease SWE in spring. On average, wintertime SWE exhibits normal gains during north-coast AR storms and above-normal gains during the south-coast AR storms. The north-coast sites are mostly lower in altitude, where warmer-than-normal conditions more frequently yield rain. During those events when heavy rain from a warm AR storm falls on a preexisting snowpack, flooding is more likely to occur. ?? 2008 American Meteorological Society.

TEST OF THE HEMISPHERIC RULE OF MAGNETIC HELICITY IN THE SUN USING THE HELIOSEISMIC AND MAGNETIC IMAGER (HMI) DATA

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

Liu, Y.; Hoeksema, J. T.; Sun, X.

Magnetic twist in solar active regions (ARs) has been found to have a hemispheric preference in sign (hemisphere rule): negative in the northern hemisphere and positive in the southern. The preference reported in previous studies ranges greatly, from ∼ 58% to 82%. In this study, we examine this hemispheric preference using vector magnetic field data taken by Helioseismic and Magnetic Imager and find that 75% ± 7% of 151 ARs studied obey the hemisphere rule, well within the preference range in previous studies. If the sample is divided into two groups—ARs having magnetic twist and writhe of the same sign andmore » having opposite signs—the strength of the hemispheric preference differs substantially: 64% ± 11% for the former group and 87% ± 8% for the latter. This difference becomes even more significant in a sub-sample of 82 ARs having a simple bipole magnetic configuration: 56% ± 16% for the ARs having the same signs of twist and writhe, and 93% with lower and upper confidence bounds of 80% and 98% for the ARs having the opposite signs. The error reported here is a 95% confidence interval. This may suggest that, prior to emergence of magnetic tubes, either the sign of twist does not have a hemispheric preference or the twist is relatively weak.« less

Novel Mechanisms in the Regulation of G Protein-coupled Receptor Trafficking to the Plasma Membrane*

PubMed Central

Tholanikunnel, Baby G.; Joseph, Kusumam; Kandasamy, Karthikeyan; Baldys, Aleksander; Raymond, John R.; Luttrell, Louis M.; McDermott, Paul J.; Fernandes, Daniel J.

2010-01-01

β2-Adrenergic receptors (β2-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated β2-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of neo-synthesized receptors to the cell surface. Since the discovery of the signal peptide, the targeting of the integral membrane proteins to plasma membrane has been thought to be determined by structural features of the amino acid sequence alone. Here we report that localization of translationally silenced β2-AR mRNA to the peripheral cytoplasmic regions is critical for receptor localization to the plasma membrane. β2-AR mRNA is recognized by the nucleocytoplasmic shuttling RNA-binding protein HuR, which silences translational initiation while chaperoning the mRNA-protein complex to the cell periphery. When HuR expression is down-regulated, β2-AR mRNA translation is initiated prematurely in perinuclear polyribosomes, leading to overproduction of receptors but defective trafficking to the plasma membrane. Our results underscore the importance of the spatiotemporal relationship between β2-AR mRNA localization, translation, and trafficking to the plasma membrane, and establish a novel mechanism whereby G protein-coupled receptor (GPCR) responsiveness is regulated by RNA-based signals. PMID:20739277

Alteration of natural (37)Ar activity concentration in the subsurface by gas transport and water infiltration.

PubMed

Guillon, Sophie; Sun, Yunwei; Purtschert, Roland; Raghoo, Lauren; Pili, Eric; Carrigan, Charles R

2016-05-01

High (37)Ar activity concentration in soil gas is proposed as a key evidence for the detection of underground nuclear explosion by the Comprehensive Nuclear Test-Ban Treaty. However, such a detection is challenged by the natural background of (37)Ar in the subsurface, mainly due to Ca activation by cosmic rays. A better understanding and improved capability to predict (37)Ar activity concentration in the subsurface and its spatial and temporal variability is thus required. A numerical model integrating (37)Ar production and transport in the subsurface is developed, including variable soil water content and water infiltration at the surface. A parameterized equation for (37)Ar production in the first 15 m below the surface is studied, taking into account the major production reactions and the moderation effect of soil water content. Using sensitivity analysis and uncertainty quantification, a realistic and comprehensive probability distribution of natural (37)Ar activity concentrations in soil gas is proposed, including the effects of water infiltration. Site location and soil composition are identified as the parameters allowing for a most effective reduction of the possible range of (37)Ar activity concentrations. The influence of soil water content on (37)Ar production is shown to be negligible to first order, while (37)Ar activity concentration in soil gas and its temporal variability appear to be strongly influenced by transient water infiltration events. These results will be used as a basis for practical CTBTO concepts of operation during an OSI. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 coherent relation between the solar wind proton speed and O{sup 7+}/O{sup 6+} ratio and its coronal sources

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

Zhao, L., E-mail: lzh@umich.edu; Landi, E.; Fisk, L. A.

We analyze the two-hour resolution solar wind proton speed (V{sub p}) and charge state ratio of O{sup 7+}/O{sup 6+} measured by ACE (SWICS and SWEPAM) from 1998 to 2011 at 1 AU. By applying a two-step mapping method, we link the solar wind in-situ observations to the corona images captured by SOHO and STEREO, in which we identify the different plasma structures, such as active regions (ARs), coronal holes (CHs) and quiet Sun regions (QS), using a classification scheme based on pixel brightness. Then we determine from which region in the corona the solar wind originates. We examine the in-situmore » properties of the solar wind streams associated with CHs, ARs and QS regions. We find that more than half of CH associated wind is actually slow wind, and O{sup 7+}/O{sup 6+} ratio has a strong coherent correlation with the location of the solar wind coronal sources. Therefore, we conclude that O{sup 7+}/O{sup 6+} ratio can be used as a much more effective discriminator to identify solar wind coronal sources region than V{sub p}.« less

77 FR 36602 - Public Notice for Waiver for Aeronautical Land-Use Assurance at Saline County Regional Airport...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Public Notice for Waiver for Aeronautical Land-Use Assurance at Saline County Regional Airport, Benton, AR AGENCY: Federal Aviation..., Benton, AR 72018, telephone (501) 672-9809, or Mr. [[Page 36603

β3-adrenergic receptor activation induces TGFβ1 expression in cardiomyocytes via the PKG/JNK/c-Jun pathway.

PubMed

Xu, Zhongcheng; Wu, Jimin; Xin, Junzhou; Feng, Yenan; Hu, Guomin; Shen, Jing; Li, Mingzhe; Zhang, Youyi; Xiao, Han; Wang, Li

2018-06-05

In heart failure, the expression of cardiac β 3 -adrenergic receptors (β 3 -ARs) increases. However, the precise role of β 3 -AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of β 3 -AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β 3 -AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β 3 -AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a β 3 -AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGFβ1 expression upon β 3 -AR activation. A protein kinase G (PKG) inhibitor also attenuated β 3 -AR-agonist-induced TGFβ1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the β 3 -AR activation in cardiomyocytes increases the expression of TGFβ1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of β 3 -AR signaling in heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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.

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).

Design and development of multilayer wideband antireflection coating and its annealing study

NASA Astrophysics Data System (ADS)

Jena, S.; Tokas, R. B.; Udupa, D. V.; Thakur, S.; Sahoo, N. K.

2018-04-01

Reflection loss occurs at the glass-air interface, limits performance of many optical devices such as eyeglass, camera lenses, and photovoltaic solar cells. Antireflection (AR) coating on the glass reduces the reflection loss and improves efficiency of such devices. In this paper, wideband AR coating in the visible region has been designed and developed using ZrO2-MgO/SiO2 multilayer. The thicknesses of individual thin layers are numerically optimized to get maximum transmission of the visible light. The optimized four thin layers have been deposited on BK7 glass substrate using electron beam evaporation technique. The measured transmission spectrum of the 4-layer AR coating is compared with that of simulated spectrum. The transmission of the single side AR coating increases by more than 3% as compared to that of bare glass substrate in the wavelength region of 470 nm - 810 nm. The wideband AR coating has been annealed at 200°C for 4 hours in ambient condition. The transmission of the AR coating decreases after the annealing, resulting degradation in its wideband AR characteristics.

Development and Validation of a Computational Model for Androgen Receptor Activity

PubMed Central

2016-01-01

Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity. PMID:27933809

[Effect of epidermal growth factor and testosterone on androgen receptor activation in urethral plate fibroblasts in hypospadias].

PubMed

Lin, Junshan; Xie, Cheng; Chen, Ruiqing; Li, Dumiao

2016-05-01

To investigate androgen receptor (AR) expression and the effect of epidermal growth factor (EGF) and testosterone on AR expression level.
 EGF or different concentrations of testosterone were incubated with the primary urethral plate fibroblasts from patients with hypospadias. The levels of AR expression in the fibroblasts were detected by immunocytochemical assays and graphical analysis.
 There was no significant difference in AR activation under physiological concentrations (3×10(-8) mol/L) of testosterone between the control and the distal hypospadias group (P>0.05). However, there was a significant decrease in AR activation in the proximal hypospadias group compared to that in the control group (P<0.001). Under the concentration of 3×10(-6) mol/L, the effects of testosterone on AR activation were dramatically different in the three groups (control group>distal hypospadias group>proximal hypospadias group, P<0.001). AR activation level in the group of proximal hypospadias was improved most obviously when EGF and physiological concentration of testosterone were employed in the urethral plate fibroblasts from hypospadias patients (P<0.001), and it was improved more in the distal hypospadias group than that in the control group (P=0.02).
 AR expression and activation in the urethral plate fibroblasts from hypospadias patients are abnormal. EGF can be used to improve AR activation in fibroblasts from different types of hypospadias, especially in the proximal type.

Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

PubMed Central

Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

2015-01-01

The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK/ERK signaling cascade that is likely independent of coupling to Gαq. PMID:25606852

Elimination of resistive losses in large-area LEDs by new diffusion-driven devices

NASA Astrophysics Data System (ADS)

Kivisaari, Pyry; Kim, Iurii; Suihkonen, Sami; Oksanen, Jani

2017-02-01

High-power operation of conventional GaN-based light-emitting diodes (LEDs) is severely limited by current crowding, which increases the bias voltage of the LED, concentrates light emission close to the p-type contact edge, and aggravates the efficiency droop. Fabricating LEDs on thick n-GaN substrates alleviates current crowding but requires the use of expensive bulk GaN substrates and fairly large n-contacts, which take away a large part of the active region (AR). In this work, we demonstrate through comparative simulations how the recently introduced diffusion-driven charge transport (DDCT) concept can be used to realize lateral heterojunction (LHJ) structures, which eliminate most of the lateral current crowding. Specifically in this work, we analyze how using a single-side graded AR can both facilitate electron and hole diffusion in DDCT and increase the effective AR thickness. Our simulations show that the increased effective AR thickness allows a substantial reduction in the efficiency droop at large currents, and that unlike conventional 2D LEDs, the LHJ structure shows practically no added efficiency loss or differential resistance due to current crowding. Furthermore, as both electrons and holes enter the AR from the same side without any notable potential barriers in the LHJ structure, the LHJ structure shows an additional wall-plug efficiency gain over the conventional structures under comparison. This injection from the same side is expected to be even more interesting in multiple quantum well structures, where carriers typically need to surpass several potential barriers in conventional LEDs before recombining. In addition to simulations, we also demonstrate selective-area growth of a finger structure suitable for operation as an LHJ device with 2µm distance between n- and p-GaN regions.

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats

PubMed Central

Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

2013-01-01

Abstract Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long‐term depression (LTD) and depotentiation (DP) by low‐frequency stimulation (LFS) and long‐term potentiation (LTP) by high‐frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS‐dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N‐methyl‐d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired‐pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity‐dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively. PMID:24744863

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.

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.

THE COLD SHOULDER: EMISSION MEASURE DISTRIBUTIONS OF ACTIVE REGION CORES

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

Schmelz, J. T.; Pathak, S., E-mail: jschmelz@memphis.edu

2012-09-10

The coronal heating mechanism for active region core loops is difficult to determine because these loops are often not resolved and cannot be studied individually. Rather, we concentrate on the 'inter-moss' areas between loop footpoints. We use observations from the Hinode EUV Imaging Spectrometer and the X-Ray Telescope to calculate the emission measure distributions of eight inter-moss areas in five different active regions. The combined data sets provide both high- and low-temperature constraints and ensure complete coverage in the temperature range appropriate for active regions. For AR 11113, the emission can be modeled with heating events that occur on timescalesmore » less than the cooling time. The loops in the core regions appear to be close to equilibrium and are consistent with steady heating. The other regions studied, however, appear to be dominated by nanoflare heating. Our results are consistent with the idea that active region age is an important parameter in determining whether steady or nanoflare heating is primarily responsible for the core emission, that is, older regions are more likely to be dominated by steady heating, while younger regions show more evidence of nanoflares.« less

CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight.

PubMed

Richard, Jennifer E; López-Ferreras, Lorena; Chanclón, Belén; Eerola, Kim; Micallef, Peter; Skibicka, Karolina P; Wernstedt Asterholm, Ingrid

2017-09-01

Pharmacological β 3 -adrenergic receptor (β 3 AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β 3 AR agonists is mediated solely through activation of β 3 ARs in adipose tissue. However, β 3 ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β 3 ARs. Therefore, this study aimed to elucidate whether CNS β 3 ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β 3 AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β 3 AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β 3 AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β 3 AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β 3 AR activation. Copyright © 2017 the American Physiological Society.

The Nonpeptide Oxytocin Receptor Agonist WAY 267,464: Receptor-Binding Profile, Prosocial Effects and Distribution of c-Fos Expression in Adolescent Rats

PubMed Central

Hicks, C.; Jorgensen, W.; Brown, C.; Fardell, J.; Koehbach, J.; Gruber, C. W.; Kassiou, M.; Hunt, G. E.; McGregor, I. S.

2012-01-01

Previous research suggests that the nonpeptide oxytocin receptor (OTR) agonist WAY 267,464 may only partly mimic the effects of oxytocin in rodents. The present study further explored these differences and related them to OTR and vasopressin 1a receptor (V1aR) pharmacology and regional patterns of c-Fos expression. Binding data for WAY 267,464 and oxytocin were obtained by displacement binding assays on cellular membranes, while functional receptor data were generated by luciferase reporter assays. For behavioural testing, adolescent rats were tested in a social preference paradigm, the elevated plus-maze (EPM) and for locomotor activity changes following WAY 267,464 (10 and 100 mg/kg, i.p.) or oxytocin (0.1 and 1 mg/kg, i.p.). The higher doses were also examined for their effects on regional c-Fos expression. Results showed that WAY 267,464 had higher affinity (Ki) at the V1aR than the OTR (113 versus 978 nm). However, it had no functional response at the V1aR and only a weak functional effect (EC50) at the OTR (881 nm). This suggests WAY 267,464 is an OTR agonist with weak affinity and a possible V1aR antagonist. Oxytocin showed high binding at the OTR (1.0 nm) and V1aR (503 nm), with a functional EC50 of 9.0 and 59.7 nm, respectively, indicating it is a potent OTR agonist and full V1aR agonist. WAY 267,464 (100 mg/kg), but not oxytocin, significantly increased the proportion of time spent with a live rat, over a dummy rat, in the social preference test. Neither compound affected EPM behaviour, whereas the higher doses of WAY 267,464 and oxytocin suppressed locomotor activity. WAY 267,464 and oxytocin produced similar c-Fos expression in the paraventricular hypothalamic nucleus, central amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, suggesting a commonality of action at the OTR with the differential doses employed. However, WAY 267,464 caused greater c-Fos expression in the medial amygdala and the supraoptic nucleus than oxytocin, and lesser effects in the locus coeruleus. Overall, our results confirm the differential effects of WAY 267,464 and oxytocin and suggest that this may reflect contrasting actions of WAY 267,464 and oxytocin at the V1aR. Antagonism of the V1aR by WAY 267,464 could underlie some of the prosocial effects of this drug either through a direct action or through disinhibition of oxytocin circuitry that is subject to vasopressin inhibitory influences. PMID:22420322

Automatic Regionalization Algorithm for Distributed State Estimation in Power Systems

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

Wang, Dexin; Yang, Liuqing; Florita, Anthony

The deregulation of the power system and the incorporation of generation from renewable energy sources recessitates faster state estimation in the smart grid. Distributed state estimation (DSE) has become a promising and scalable solution to this urgent demand. In this paper, we investigate the regionalization algorithms for the power system, a necessary step before distributed state estimation can be performed. To the best of the authors' knowledge, this is the first investigation on automatic regionalization (AR). We propose three spectral clustering based AR algorithms. Simulations show that our proposed algorithms outperform the two investigated manual regionalization cases. With the helpmore » of AR algorithms, we also show how the number of regions impacts the accuracy and convergence speed of the DSE and conclude that the number of regions needs to be chosen carefully to improve the convergence speed of DSEs.« less

Automatic Regionalization Algorithm for Distributed State Estimation in Power Systems: Preprint

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

Wang, Dexin; Yang, Liuqing; Florita, Anthony

The deregulation of the power system and the incorporation of generation from renewable energy sources recessitates faster state estimation in the smart grid. Distributed state estimation (DSE) has become a promising and scalable solution to this urgent demand. In this paper, we investigate the regionalization algorithms for the power system, a necessary step before distributed state estimation can be performed. To the best of the authors' knowledge, this is the first investigation on automatic regionalization (AR). We propose three spectral clustering based AR algorithms. Simulations show that our proposed algorithms outperform the two investigated manual regionalization cases. With the helpmore » of AR algorithms, we also show how the number of regions impacts the accuracy and convergence speed of the DSE and conclude that the number of regions needs to be chosen carefully to improve the convergence speed of DSEs.« less

TIME DEPENDENT NONEQUILIBRIUM IONIZATION OF TRANSITION REGION LINES OBSERVED WITH IRIS

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

Martínez-Sykora, Juan; Pontieu, Bart De; Hansteen, Viggo H.

The properties of nonstatistical equilibrium ionization of silicon and oxygen ions are analyzed in this work. We focus on five solar targets (quiet Sun; coronal hole; plage; quiescent active region, AR; and flaring AR) as observed with the Interface Region Imaging Spectrograph (IRIS). IRIS is best suited for this work owing to the high cadence (up to 0.5 s), high spatial resolution (up to 0.″32), and high signal-to-noise ratios for O iv λ1401 and Si iv λ1402. We find that the observed intensity ratio between lines of three times ionized silicon and oxygen ions depends on their total intensity and that this correlationmore » varies depending on the region observed (quiet Sun, coronal holes, plage, or active regions) and on the specific observational objects present (spicules, dynamic loops, jets, microflares, or umbra). In order to interpret the observations, we compare them with synthetic profiles taken from 2D self-consistent radiative MHD simulations of the solar atmosphere, where the statistical equilibrium or nonequilibrium treatment of silicon and oxygen is applied. These synthetic observations show vaguely similar correlations to those in the observations, i.e., between the intensity ratios and their intensities, but only in the nonequilibrium case do we find that (some of) the observations can be reproduced. We conclude that these lines are formed out of statistical equilibrium. We use our time-dependent nonequilibrium ionization simulations to describe the physical mechanisms behind these observed properties.« less

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

Electric currents and coronal heating in NOAA active region 6952

NASA Technical Reports Server (NTRS)

Metcalf, T. R.; Canfield, R. C.; Hudson, H. S.; Mickey, D. L.; Wulser, J. -P.; Martens, P. C. H.; Tsuneta, S.

1994-01-01

We examine the spatial and temporal relationship between coronal structures observed with the soft X-ray telescope (SXT) on board the Yohkoh spacecraft and the vertical electric current density derived from photospheric vector magnetograms obtained using the Stokes Polarimeter at the Mees Solar Observatory. We focus on a single active region: AR 6952 which we observed on 7 days during 1991 December. For 11 independent maps of the vertical electric current density co-aligned with non-flaring X-ray images, we search for a morphological relationship between sites of high vertical current density in the photosphere and enhanced X-ray emission in the overlying corona. We find no compelling spatial or temporal correlation between the sites of vertical current and the bright X-ray structures in this active region.

Screening and Characterization of Polygalacturonase as Potential Enzyme for Keprok Garut Orange (Citrus nobilis var. chrysocarpa) Juice Clarification

NASA Astrophysics Data System (ADS)

Widowati, E.; Utami, R.; Kalistyatika, K.

2017-11-01

Use of thermostable enzyme from bacilli for industrial application is significant. This research aimed to isolate thermophilic pectinolytic bacteria from orange peel and vegetable waste which produced thermostable polygalacturonase, to investigate the polygalacturonase ability in clarifying keprok Garut orange juice, and to characterize polygalacturonase based on pH optimum, temperature optimum, enzyme stability, enzyme kinetics KM, and Vmax. Obtained, 14 isolates that further selected to 4 best isolates based on highest polygalacturonase activity and keprok Garut orange juice clarification ability. Four selected enzyme isolates were AR 2, AR 4, KK 4, and KK 5 had ability to increase juice transmittance, decrease juice viscosity and also reduce total soluble solid. Furthermore 4 selected isolates were partially purified by ammonium sulphate precipitation and dialysis method. Four partially purified enzymes were known that enzyme character of AR 2 optimum at pH 6; AR 4 optimum at pH 5.5; KK 4 optimum at pH 6; and KK 5 optimum at pH 4.5. Four enzymes were optimum at temperature 60°C thus stable at temperature 50-60°C, this characteristic indicate that enzymes were thermostable. AR 2 showed active activity stable at pH 4-7; AR 4 showed active activity stable at pH 6-7; KK 4 showed active activity stable at pH 4-6; however KK 5 stable at pH 4-5. Enzyme AR 2 and KK 4 was getting inactive at pH 11, thus AR 4 and KK 5 inactive at pH 12. KM value of AR 2, AR 4, KK 4, and KK 5 was 0.0959; 0.0974; 0.0966; and 0.178 mg/ml respectively. Vmax of AR 2, AR 4, KK 4, and KK 5 was 0.0203; 0.0202; 0.0185; and 0.0229 U/ml respectively. Enzyme AR 2 was the most compatible enzyme to be applied in keprok Garut orange juice clarification for it had the lowest KM value.

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

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

Magnetohydrodynamic Modeling of Solar Coronal Dynamics with an Initial Non-force-free Magnetic Field

NASA Astrophysics Data System (ADS)

Prasad, A.; Bhattacharyya, R.; Kumar, Sanjay

2017-05-01

The magnetic fields in the solar corona are generally neither force-free nor axisymmetric and have complex dynamics that are difficult to characterize. Here we simulate the topological evolution of solar coronal magnetic field lines (MFLs) using a magnetohydrodynamic model. The simulation is initialized with a non-axisymmetric non-force-free magnetic field that best correlates with the observed vector magnetograms of solar active regions (ARs). To focus on these ideas, simulations are performed for the flaring AR 11283 noted for its complexity and well-documented dynamics. The simulated dynamics develops as the initial Lorentz force pushes the plasma and facilitates successive magnetic reconnections at the two X-type null lines present in the initial field. Importantly, the simulation allows for the spontaneous development of mass flow, unique among contemporary works, that preferentially reconnects field lines at one of the X-type null lines. Consequently, a flux rope consisting of low-lying twisted MFLs, which approximately traces the major polarity inversion line, undergoes an asymmetric monotonic rise. The rise is attributed to a reduction in the magnetic tension force at the region overlying the rope, resulting from the reconnection. A monotonic rise of the rope is in conformity with the standard scenario of flares. Importantly, the simulated dynamics leads to bifurcations of the flux rope, which, being akin to the observed filament bifurcation in AR 11283, establishes the appropriateness of the initial field in describing ARs.

Magnetohydrodynamic Modeling of Solar Coronal Dynamics with an Initial Non-force-free Magnetic Field

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

Prasad, A.; Bhattacharyya, R.; Kumar, Sanjay

The magnetic fields in the solar corona are generally neither force-free nor axisymmetric and have complex dynamics that are difficult to characterize. Here we simulate the topological evolution of solar coronal magnetic field lines (MFLs) using a magnetohydrodynamic model. The simulation is initialized with a non-axisymmetric non-force-free magnetic field that best correlates with the observed vector magnetograms of solar active regions (ARs). To focus on these ideas, simulations are performed for the flaring AR 11283 noted for its complexity and well-documented dynamics. The simulated dynamics develops as the initial Lorentz force pushes the plasma and facilitates successive magnetic reconnections atmore » the two X-type null lines present in the initial field. Importantly, the simulation allows for the spontaneous development of mass flow, unique among contemporary works, that preferentially reconnects field lines at one of the X-type null lines. Consequently, a flux rope consisting of low-lying twisted MFLs, which approximately traces the major polarity inversion line, undergoes an asymmetric monotonic rise. The rise is attributed to a reduction in the magnetic tension force at the region overlying the rope, resulting from the reconnection. A monotonic rise of the rope is in conformity with the standard scenario of flares. Importantly, the simulated dynamics leads to bifurcations of the flux rope, which, being akin to the observed filament bifurcation in AR 11283, establishes the appropriateness of the initial field in describing ARs.« less

Synthesis, Antibacterial Evaluation and QSAR of α-Substituted-N4-Acetamides of Ciprofloxacin and Norfloxacin

PubMed Central

Qandil, Amjad M.; Al-Zoubi, Lorca O.; Al-Bakri, Amal G.; Amawi, Haneen A.; Al-Balas, Qosay A.; Alkatheri, Abdulmalik M.; Albekairy, Abdulkareem M.

2014-01-01

Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 μM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity. PMID:27025747

Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52.

PubMed

Joshi, Jugal Bharat; Patel, Divya; Morton, Derrick J; Sharma, Pankaj; Zou, Jin; Hewa Bostanthirige, Dhanushka; Gorantla, Yamini; Nagappan, Peri; Komaragiri, Shravan Kumar; Sivils, Jeffrey C; Xie, Huan; Palaniappan, Ravi; Wang, Guangdi; Cox, Marc B; Chaudhary, Jaideep

2017-04-01

Castration-resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen-depleted environment of the prostate. In recent years, targeting multiple chaperones and co-chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant-negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice. In this study, we investigated the underlying mechanism through which loss of ID4 potentiates AR signaling. Proteomic analysis between prostate cancer cell line LNCaP (L+ns) and LNCaP lacking ID4 (L(-)ID4) revealed elevated levels of Hsp27 and FKBP52, suggesting a role for these AR-associated co-chaperones in promoting constitutively active AR signaling in L(-)ID4 cells. Interestingly, protein interaction studies demonstrated a direct interaction between ID4 and the 52-kDa FK506-binding protein (FKBP52) in vitro, but not with AR. An increase in FKBP52-dependent AR transcriptional activity was observed in L(-)ID4 cells. Moreover, pharmacological inhibition of FKBP52-AR signaling, by treatment with MJC13, attenuated the tumor growth, weight, and volume in L(-)ID4 xenografts. Together, our results demonstrate that ID4 selectively regulates AR activity through direct interaction with FKBP52, and its loss, promotes CRPC through FKBP52-mediated AR signaling. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells.

PubMed

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein.

HMI Data Driven Magnetohydrodynamic Model Predicted Active Region Photospheric Heating Rates: Their Scale Invariant, Flare Like Power Law Distributions, and Their Possible Association With Flares

NASA Technical Reports Server (NTRS)

Goodman, Michael L.; Kwan, Chiman; Ayhan, Bulent; Shang, Eric L.

2017-01-01

There are many flare forecasting models. For an excellent review and comparison of some of them see Barnes et al. (2016). All these models are successful to some degree, but there is a need for better models. We claim the most successful models explicitly or implicitly base their forecasts on various estimates of components of the photospheric current density J, based on observations of the photospheric magnetic field B. However, none of the models we are aware of compute the complete J. We seek to develop a better model based on computing the complete photospheric J. Initial results from this model are presented in this talk. We present a data driven, near photospheric, 3 D, non-force free magnetohydrodynamic (MHD) model that computes time series of the total J, and associated resistive heating rate in each pixel at the photosphere in the neutral line regions (NLRs) of 14 active regions (ARs). The model is driven by time series of B measured by the Helioseismic & Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. Spurious Doppler periods due to SDO orbital motion are filtered out of the time series of B in every AR pixel. Errors in B due to these periods can be significant.

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

Heterologous desensitization of cardiac β-adrenergic signal via hormone-induced βAR/arrestin/PDE4 complexes

PubMed Central

Shi, Qian; Li, Minghui; Mika, Delphine; Fu, Qin; Kim, Sungjin; Phan, Jason; Shen, Ao; Vandecasteele, Gregoire; Xiang, Yang K.

2017-01-01

Aims Cardiac β-adrenergic receptor (βAR) signalling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Methods and results Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists. Activation of Gs-coupled dopamine receptor, adenosine receptor, relaxin receptor and prostaglandin E2 receptor, and Gq-coupled α1 adrenergic receptor and angiotensin II type 1 receptor promotes phosphorylation of β1AR and β2AR at putative protein kinase A (PKA) phosphorylation sites; but activation of Gi-coupled α2 adrenergic receptor and activation of protease-activated receptor does not. The GPCR agonists that promote β2AR phosphorylation effectively inhibit βAR agonist isoproterenol-induced PKA phosphorylation of phospholamban and contractile function in ventricular cardiomyocytes. Heterologous GPCR stimuli have minimal to small effect on isoproterenol-induced β2AR activation and G-protein coupling for cyclic adenosine monophosphate (cAMP) production. However, these GPCR stimuli significantly promote phosphorylation of phosphodiesterase 4D (PDE4D), and recruit PDE4D to the phosphorylated β2AR in a β-arrestin 2 dependent manner without promoting β2AR endocytosis. The increased binding between β2AR and PDE4D effectively hydrolyzes cAMP signal generated by subsequent stimulation with isoproterenol. Mutation of PKA phosphorylation sites in β2AR, inhibition of PDE4, or genetic ablation of PDE4D or β-arrestin 2 abolishes this heterologous inhibitory effect. Ablation of β-arrestin 2 or PDE4D gene also rescues β-adrenergic stimuli-induced myocyte contractile function. Conclusions These data reveal essential roles of β-arrestin 2 and PDE4D in a common mechanism for heterologous desensitization of cardiac βARs under hormonal stimulation, which is associated with impaired cardiac function during the development of pathophysiological conditions. PMID:28339772

Heterologous desensitization of cardiac β-adrenergic signal via hormone-induced βAR/arrestin/PDE4 complexes.

PubMed

Shi, Qian; Li, Minghui; Mika, Delphine; Fu, Qin; Kim, Sungjin; Phan, Jason; Shen, Ao; Vandecasteele, Gregoire; Xiang, Yang K

2017-05-01

Cardiac β-adrenergic receptor (βAR) signalling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists. Activation of Gs-coupled dopamine receptor, adenosine receptor, relaxin receptor and prostaglandin E2 receptor, and Gq-coupled α1 adrenergic receptor and angiotensin II type 1 receptor promotes phosphorylation of β1AR and β2AR at putative protein kinase A (PKA) phosphorylation sites; but activation of Gi-coupled α2 adrenergic receptor and activation of protease-activated receptor does not. The GPCR agonists that promote β2AR phosphorylation effectively inhibit βAR agonist isoproterenol-induced PKA phosphorylation of phospholamban and contractile function in ventricular cardiomyocytes. Heterologous GPCR stimuli have minimal to small effect on isoproterenol-induced β2AR activation and G-protein coupling for cyclic adenosine monophosphate (cAMP) production. However, these GPCR stimuli significantly promote phosphorylation of phosphodiesterase 4D (PDE4D), and recruit PDE4D to the phosphorylated β2AR in a β-arrestin 2 dependent manner without promoting β2AR endocytosis. The increased binding between β2AR and PDE4D effectively hydrolyzes cAMP signal generated by subsequent stimulation with isoproterenol. Mutation of PKA phosphorylation sites in β2AR, inhibition of PDE4, or genetic ablation of PDE4D or β-arrestin 2 abolishes this heterologous inhibitory effect. Ablation of β-arrestin 2 or PDE4D gene also rescues β-adrenergic stimuli-induced myocyte contractile function. These data reveal essential roles of β-arrestin 2 and PDE4D in a common mechanism for heterologous desensitization of cardiac βARs under hormonal stimulation, which is associated with impaired cardiac function during the development of pathophysiological conditions. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men.

PubMed

Manuck, Stephen B; Marsland, Anna L; Flory, Janine D; Gorka, Adam; Ferrell, Robert E; Hariri, Ahmad R

2010-01-01

In studies employing functional magnetic resonance imaging (fMRI), reactivity of the amygdala to threat-related sensory cues (viz., facial displays of negative emotion) has been found to correlate positively with interindividual variability in testosterone levels of women and young men and to increase on acute administration of exogenous testosterone. Many of the biological actions of testosterone are mediated by intracellular androgen receptors (ARs), which exert transcriptional control of androgen-dependent genes and are expressed in various regions of the brain, including the amygdala. Transactivation potential of the AR decreases (yielding relative androgen insensitivity) with expansion a polyglutamine stretch in the N-terminal domain of the AR protein, as encoded by a trinucleotide (CAG) repeat polymorphism in exon 1 of the X-chromosome AR gene. Here we examined whether amygdala reactivity to threat-related facial expressions (fear, anger) differs as a function of AR CAG length variation and endogenous (salivary) testosterone in a mid-life sample of 41 healthy men (mean age=45.6 years, range: 34-54 years; CAG repeats, range: 19-29). Testosterone correlated inversely with participant age (r=-0.39, p=0.012) and positively with number of CAG repeats (r=0.45, p=0.003). In partial correlations adjusted for testosterone level, reactivity in the ventral amygdala was lowest among men with largest number of CAG repeats. This inverse association was seen in both the right (r(p)=-0.34, p<0.05) and left (r(p)=-0.32, p<0.05) hemisphere. Activation of dorsal amygdala, correlated positively with individual differences in salivary testosterone, also in right (r=0.40, p<0.02) and left (r=0.32, p<0.05) hemisphere, but was not affected by number of CAG repeats. Hence, androgenic influences on threat-related reactivity in the ventral amygdala may be moderated partially by CAG length variation in the AR gene. Because individual differences in salivary testosterone also predicted dorsal amygdala reactivity and did so independently of CAG repeats, it is suggested that androgenic influences within this anatomically distinct region may be mediated, in part, by non-genomic or AR-independent mechanisms.

History of cotton fiber bioscience research at USDA-ARS Southern Regional Research Center

USDA-ARS?s Scientific Manuscript database

Improving fiber quality has been an important breeding goal for cotton breeders. Better understanding of fiber development helps cotton scientists to devise a strategy for crop improvement either through marker-assisted selection or via manipulation of fiber genes. USDA-ARS Southern Regional Researc...

76 FR 43336 - Agency Information Collection Activities: Form AR-11, Extension of an Existing Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... Collection Activities: Form AR-11, Extension of an Existing Information Collection; Comment Request ACTION: 30-Day Notice of Information Collection under Review: Form AR- 11, Alien's Change of Address Card... collection: Form AR-11. U.S. Citizenship and Immigration Services. (4) Affected public who will be asked or...

Modeling study of radiation characteristics with different impurity species seeding in EAST

NASA Astrophysics Data System (ADS)

Liu, X. J.; Deng, G. Z.; Wang, L.; Liu, S. C.; Zhang, L.; Li, G. Q.; Gao, X.

2017-12-01

A critical issue for EAST and future tokamak machines such as ITER and China Fusion Engineering Testing Reactor is the handling of excessive heat load on the divertor target plates. As an effective means of actively reducing and controlling the power fluxes to the target plates, localized impurity (N, Ne, and Ar) gas puffing from the lower dome is investigated by using SOLPS5.0 for an L-mode discharge on EAST with double null configuration. The radiative efficiency and distribution of different impurities are compared. The effect of N, Ne, and Ar seeding on target power load, the power entering into scrape-off layer (SOL), Psep, and their concentration in SOL along the poloidal length and edge effective ion charge number (Zeff) which are closely related to core plasma performance are presented. The simulation results indicate that N, Ne, and Ar seeding can effectively reduce the peak heat load and electron temperature at divertor targets similarly. N seeding can reach the highest radiative loss fraction and both N and Ar strongly radiate power in the divertor region, while the radiative power inside the separatrix for Ar seeding is also significant. Ne radiates power mainly around the separatrix and X-point. Ne and Ar impurities' puffing results in a faster decrease of Psep than N seeding case; the reduction of Psep can eventually degrade the core performance of fusion plasma. Additionally, seeding with Ne has a totally larger concentration at the outer midplane and edge Zeff than those in N and Ar seeding cases; it suggests that N and Ar impurities are more acceptable than Ne in terms of fuel dilution for this discharge.

FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer

PubMed Central

2014-01-01

Background Increasing evidence suggests that forkhead box A1 (FOXA1) is frequently dysregulated in many types of human cancers. However, the exact function and mechanism of FOXA1 in human endometrial cancer (EC) remains unclear. Methods FOXA1 expression, androgen receptor (AR) expression, and the relationships of these two markers with clinicopathological factors were determined by immunohistochemistry analysis. FOXA1 and AR were up-regulated by transient transfection with plasmids, and were down-regulated by transfection with siRNA or short hairpin RNA (shRNA). The effects of FOXA1 depletion and FOXA1 overexpression on AR-mediated transcription as well as Notch pathway and their impact on EC cell proliferation were examined by qRT-PCR, western blotting, co-immunoprecipitation, ChIP-PCR, MTT, colony-formation, and xenograft tumor–formation assays. Results We found that the expression of FOXA1 and AR in ECs was significantly higher than that in a typical hyperplasia and normal tissues. FOXA1 expression was significantly correlated with AR expression in clinical tissues. High FOXA1 levels positively correlated with pathological grade and depth of myometrial invasion in EC. High AR levels also positively correlated with pathological grade in EC. Moreover, the expression of XBP1, MYC, ZBTB16, and UHRF1, which are downstream targets of AR, was promoted by FOXA1 up-regulation or inhibited by FOXA1 down-regulation. Co-immunoprecipitation showed that FOXA1 interacted with AR in EC cells. ChIP-PCR assays showed that FOXA1 and AR could directly bind to the promoter and enhancer regions upstream of MYC. Mechanistic investigation revealed that over-expression of Notch1 and Hes1 proteins by FOXA1 could be reversed by AR depletion. In addition, we showed that down-regulation of AR attenuated FOXA1-up-regulated cell proliferation. However, AR didn’t influence the promotion effect of FOXA1 on cell migration and invasion. In vivo xenograft model, FOXA1 knockdown reduced the rate of tumor growth. Conclusions These results suggest that FOXA1 promotes cell proliferation by AR and activates Notch pathway. It indicated that FOXA1 and AR may serve as potential gene therapy in EC. PMID:24512546

Translation, Cross-Cultural Adaptation, and Validation of the Activity Rating Scale for Disorders of the Knee

PubMed Central

Flosadottir, Vala; Roos, Ewa M.; Ageberg, Eva

2017-01-01

Background: The Activity Rating Scale (ARS) for disorders of the knee evaluates the level of activity by the frequency of participation in 4 separate activities with high demands on knee function, with a score ranging from 0 (none) to 16 (pivoting activities 4 times/wk). Purpose: To translate and cross-culturally adapt the ARS into Swedish and to assess measurement properties of the Swedish version of the ARS. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The COSMIN guidelines were followed. Participants (N = 100 [55 women]; mean age, 27 years) who were undergoing rehabilitation for a knee injury completed the ARS twice for test-retest reliability. The Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale (TAS), and modernized Saltin-Grimby Physical Activity Level Scale (SGPALS) were administered at baseline to validate the ARS. Construct validity and responsiveness of the ARS were evaluated by testing predefined hypotheses regarding correlations between the ARS, KOOS, TAS, and SGPALS. The Cronbach alpha, intraclass correlation coefficients, absolute reliability, standard error of measurement, smallest detectable change, and Spearman rank-order correlation coefficients were calculated. Results: The ARS showed good internal consistency (α ≈ 0.96), good test-retest reliability (intraclass correlation coefficient >0.9), and no systematic bias between measurements. The standard error of measurement was less than 2 points, and the smallest detectable change was less than 1 point at the group level and less than 5 points at the individual level. More than 75% of the hypotheses were confirmed, indicating good construct validity and good responsiveness of the ARS. Conclusion: The Swedish version of the ARS is valid, reliable, and responsive for evaluating the level of activity based on the frequency of participation in high-demand knee sports activities in young adults with a knee injury. PMID:28979920

Winter precipitation characteristics in western US related to atmospheric river landfalls: observations and model evaluations

NASA Astrophysics Data System (ADS)

Kim, J.; Guan, B.; Waliser, D. E.; Ferraro, R. D.; Case, J. L.; Iguchi, T.; Kemp, E.; Putman, W.; Wang, W.; Wu, D.; Tian, B.

2018-01-01

Winter precipitation (PR) characteristics in western United States (WUS) related to atmospheric river (AR) landfalls are examined using the observation-based PRISM data. The observed AR-related precipitation characteristics are in turn used to evaluate model precipitation data from the NASA MERRA2 reanalysis and from seven dynamical downscaling simulations driven by the MERRA2. Multiple metrics including mean bias, Taylor diagram, and two skill scores are used to measure model performance for three climatological sub-regions in WUS, Pacific Northwest (PNW), Pacific Southwest (PSW) and Great Basin (GB). All model data well represent the winter-mean PR with spatial pattern correlations of 0.8 or higher with PRISM for the three sub-regions. Higher spatial resolutions and/or the use of spectral nudging generally yield higher skill scores in simulating the geographical distribution of PR for the entire winter. The PRISM data shows that the AR-related fraction of winter PR and associated daily PR PDFs in each region vary strongly for landfall locations; AR landfalls in the northern WUS coast (NC) affect mostly PNW while those in the southern WUS coast (SC) affect both PSW and GB. NC (SC) landfalls increase the frequency of heavy PR in PNW (PSW and GB) but reduce it in PSW (PNW). All model data reasonably represent these observed variations in the AR-related winter PR fractions and the daily PR PDFs according to AR landfall locations. However, unlike for the entire winter period, no systematic effects of resolution and/or spectral nudging are identified in these AR-related PR characteristics. Dynamical downscaling in this study generally yield positive added values to the MERRA2 PR in the AR-related PR fraction for most sub-regions and landfall locations, most noticeably for PSW by NU-WRF. The downscaling also generate positive added value in p95 for PNW, but negative values for PSW and GB due to overestimation of heavy precipitation events.

Raf kinase inhibitor protein: lessons of a better way for β‐adrenergic receptor activation in the heart

PubMed Central

Rosner, Marsha Rich; Brand, Theresa; Schmitt, Joachim P

2017-01-01

Abstract Stimulation of β‐adrenergic receptors (βARs) provides the most efficient physiological mechanism to enhance contraction and relaxation of the heart. Activation of βARs allows rapid enhancement of myocardial function in order to fuel the muscles for running and fighting in a fight‐or‐flight response. Likewise, βARs become activated during cardiovascular disease in an attempt to counteract the restrictions of cardiac output. However, long‐term stimulation of βARs increases the likelihood of cardiac arrhythmias, adverse ventricular remodelling, decline of cardiac performance and premature death, thereby limiting the use of βAR agonists in the treatment of heart failure. Recently the endogenous Raf kinase inhibitor protein (RKIP) was found to activate βAR signalling of the heart without adverse effects. This review will summarize the current knowledge on RKIP‐driven compared to receptor‐mediated signalling in cardiomyocytes. Emphasis is given to the differential effects of RKIP on β1‐ and β2‐ARs and their downstream targets, the regulation of myocyte calcium cycling and myofilament activity. PMID:28444807

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

Mebarki, F.; Forest, M.G.; Josso, N.

The androgen insensivity syndrome (AIS) is a recessive X-linked disorder resulting from a deficient function of the androgen receptor (AR). The human AR gene has 3 functional domains: N-terminal encoded by exon 1, DNA-binding domain encoded by exons 2 and 3, and androgen-binding domain encoded by exons 4 to 8. In order to characterize the molecular defects of the AR gene in AIS, the entire coding regions and the intronic bording sequences of the AR gene were amplified by PCR before automatic direct sequencing in 45 patients. Twenty seven different point mutations were found in 32 unrelated AIS patients: 18more » with a complete form (CAIS), 14 with a partial form (PAIS); 18 of these mutations are novel mutations, not published to date. Only 3 mutations were repeatedly found: R804H in 3 families; M780I in 3 families and R774C in 2 families. For 26 patients out of the 32 found to have a mutation, maternal DNA was collected and sequenced: 6 de novo mutations were detected (i.e. 23% of the cases). Finally, no mutation was detected in 13 patients (29%): 7 with CAIS and 6 familial severe PAIS. The latter all presented with perineal hypospadias, micropenis, 4 out of 6 being raised as girl. Diagnosis of AIS in these 13 families in whom no mutation was detected is supported by the following criteria: clinical data, familial history (2 or 3 index cases in the same family), familial segregation of the polymorphic CAG repeat of the AR gene. Mutations in intronic regions or the promoter of the AR gene could not explain all cases of AIS without mutations in the AR coding regions, because AR binding (performed in 9 out of 13) was normal in 6, suggesting the synthesis of an AR protein. This situation led us to speculate that another X-linked factor associated with the AR could be implicated in some cases of AIS.« less

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

Hall, Jeter C.; Aalseth, Craig E.; Bonicalzi, Ricco

Age dating groundwater and seawater using 39Ar/Ar ratios is an important tool to understand water mass flow rates and mean residence time. For modern or contemporary argon, the 39Ar activity is 1.8 mBq per liter of argon. Radiation measurements at these activity levels require ultra low-background detectors. Low-background proportional counters have been developed at Pacific Northwest National Laboratory. These detectors use traditional mixtures of argon and methane as counting gas, and the residual 39Ar from commercial argon has become a predominant source of background activity in these detectors. We demonstrated sensitivity to 39Ar by using geological or ancient argon frommore » gas wells in place of commercial argon. The low level counting performance of these proportional counters is then demonstrated for sensitivities to 39Ar/Ar ratios sufficient to date water masses as old as 1000 years.« less

Tephra layers of blind Spring Valley and related upper pliocene and pleistocene tephra layers, California, Nevada, and Utah: isotopic ages, correlation, and magnetostratigraphy

USGS Publications Warehouse

Sarna-Wojcicki, Andrei M.; Reheis, Marith C.; Pringle, Malcolm S.; Fleck, Robert J.; Burbank, Doug; Meyer, Charles E.; Slate, Janet L.; Wan, Elmira; Budahn, James R.; Troxel, Bennie; Walker, James P.

2005-01-01

Numerical ages have been determined for a stratigraphic sequence of silicic tephra layers exposed at the Cowan Pumice Mine in Blind Spring Valley, near Benton Hot Springs, east-central California, as well as at Chalk Cliffs, north of Bishop, Calif. The tephra layers at these sites were deposited after eruptions from nearby sources, most of them from near Glass Mountain, and some from unknown sources. The ages were determined primarily by the laser-fusion 40Ar/39Ar method, mostly on sanidine feldspar; two were determined by conventional K-Ar analysis on obsidian clasts. These tephra layers, all underlying the Bishop ash bed and listed in order of concordant age and stratigraphic position, are: Tephra Unit Method Material Age Bishop Tuff (air-fall pumice) Ar/Ar sanidine 0.759?0.002 Ma* Upper tuffs of Glass Mountain Ar/Ar sanidine 0.87?0.02 Ma Upper tuffs of Glass Mountain Ar/Ar sanidine 1.13?0.19 Ma Lower tuffs of Glass Mountain K-Ar obsidian 1.86?0.09 Ma (avg of 2 dates) Ar/Ar sanidine 1.92?0.02 Ma (avg of 2 dates) Tuffs of Blind Spring Valley Ar/Ar sanidine 2.135?0.02 to sanidine 2.219?0.006 Ma (10 dates) Tuffs of Benton Hot Springs Ar/Ar plagioclase 2.81?0.02 Ma *Date published previously The above tephra layers were also petrographically examined and the volcanic glass shards of the layers were chemically analyzed using the electron microprobe and, for some samples, instrumental neutron activation analysis and X-ray fluorescence. The same types of chemical and petrographic analyses were conducted on stratigraphic sequences of tephra layers of suspected upper Pliocene and Pleistocene age in several past and present depositional basins within the region outside of Blind Spring Valley. Chemical characterization, combined with additional dates and with magnetostratigraphy of thick sections at two of the distal sites, allow correlation of the tephra layers at the Cowan Pumice Mine with layers present at the distal sites and provide age constraints for other intercalated tephra layers and sediments for which age data were previously lacking. The identification at several sections of the widespread Huckleberry Ridge ash bed, derived from the Yellowstone eruptive source area in Wyoming, as well as a new 40Ar/39Ar age on this ash bed from a proximal locality, provide additional age constraints to several of the distal sections. The dated or temporally bracketed distal units, in order of concordant age and stratigraphic position, are: Tephra Unit Method Material Age Tephra layers of Glass Mountain (undiff.) P-mag.*; correlation N/A 1.78 , 1.96, 1.96, 2.22, 2.57, <2.89 Ma Tephra layers of Benton Hot Springs Ar/Ar; correlation plagioclase 2.89?0.03 Ma *Magnetostratigraphic polarity determination At the Cowan Pumice Mine, only a partial section of the eruptive record is preserved, but the best materials for laser-fusion 40Ar/39Ar and other isotopic dating methods were obtained. In the more distal Willow Wash and Confidence Hills sections, both persistent depositional basins for most of late Pliocene time, more complete sections of upper Pliocene tephra layers were preserved. In the region of Glass Mountain, the tephra layers that make up each of the mapped and dated pyroclastic units are multiple and complex, but a progressive simplification of the stratigraphy away from the source area was observed for more distal sites in southern and southwestern California and in Utah. This progressive

Simulating the Coronal Evolution of AR 11437 Using SDO/HMI Magnetograms

NASA Astrophysics Data System (ADS)

Yardley, Stephanie L.; Mackay, Duncan H.; Green, Lucie M.

2018-01-01

The coronal magnetic field evolution of AR 11437 is simulated by applying the magnetofrictional relaxation technique of Mackay et al. A sequence of photospheric line-of-sight magnetograms produced by the Solar Dynamics Observatory (SDO)/Helioseismic Magnetic Imager (HMI) is used to drive the simulation and continuously evolve the coronal magnetic field of the active region through a series of nonlinear force-free equilibria. The simulation is started during the first stages of the active region emergence so that its full evolution from emergence to decay can be simulated. A comparison of the simulation results with SDO/Atmospheric Imaging Assembly (AIA) observations show that many aspects of the active region’s observed coronal evolution are reproduced. In particular, it shows the presence of a flux rope, which forms at the same location as sheared coronal loops in the observations. The observations show that eruptions occurred on 2012 March 17 at 05:09 UT and 10:45 UT and on 2012 March 20 at 14:31 UT. The simulation reproduces the first and third eruption, with the simulated flux rope erupting roughly 1 and 10 hr before the observed ejections, respectively. A parameter study is conducted where the boundary and initial conditions are varied along with the physical effects of Ohmic diffusion, hyperdiffusion, and an additional injection of helicity. When comparing the simulations, the evolution of the magnetic field, free magnetic energy, relative helicity and flux rope eruption timings do not change significantly. This indicates that the key element in reproducing the coronal evolution of AR 11437 is the use of line-of-sight magnetograms to drive the evolution of the coronal magnetic field.

The transcriptional programme of the androgen receptor (AR) in prostate cancer.

PubMed

Lamb, Alastair D; Massie, Charlie E; Neal, David E

2014-03-01

The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors. © 2013 The Authors. BJU International © 2013 BJU International.

Replacement of arginine 773 by cysteine or histidine in the human androgen receptor causes complete androgen insensitivity with different receptor phenotypes

PubMed Central

Prior, Lynn; Bordet, Sylvie; Trifiro, Mark A.; Mhatre, Anand; Kaufman, Morris; Pinsky, Leonard; Wrogeman, Klaus; Belsham, Denise D.; Pereira, Fred; Greenberg, Cheryl; Trapman, Jan; Brinkman, Albert O.; Chang, Chawnshang; Liao, Shutsung

1992-01-01

We have discovered two different point mutations in a single codon of the X-linked androgen-receptor (AR) gene in two pairs of unrelated families who have complete androgen insensitivity (resistance) associated with different AR phenotypes in their genital skin fibroblasts. One mutation is a C-to-T transition at a CpG sequence near the 5' terminus of exon 6; it changes the sense of codon 773 from arginine to cysteine, ablates specific androgen-binding activity at 37°C, and eliminates a unique KpnI site at the intron-exon boundary. The other mutation is a G-to-A transition that changes amino acid 773 to histidine and eliminates an SphI site. This mutant AR has a normal androgen-binding capacity at 37°C but has a reduced affinity for androgens and is thermolabile in their presence. Transient transfection of COS cells with cDNA expression vectors yielded little androgen-binding activity at 37°C from Arg773Cys and abundant activity with abnormal properties from Arg773His, thereby proving the pathogenicity of both sequence alterations. This conclusion coincides with the following facts about evolutionary preservation of the position homologous to Arg773 in the AR: it is occupied by Arg or lysine in the progesterone, glucocorticoid, and mineralocorticoid receptors, and it is within a 14-amino-acid region of their steroid-binding domains that share ∼85% amino acid identity. ImagesFigure 7Figure 2Figure 3Figure 5Figure 6Figure 8 PMID:1609793

Smoking-associated lung cancer prevention by blockade of the beta-adrenergic receptor-mediated insulin-like growth factor receptor activation.

PubMed

Min, Hye-Young; Boo, Hye-Jin; Lee, Ho Jin; Jang, Hyun-Ji; Yun, Hye Jeong; Hwang, Su Jung; Smith, John Kendal; Lee, Hyo-Jong; Lee, Ho-Young

2016-10-25

Activation of receptor tyrosine kinases (RTKs) is associated with carcinogenesis, but its contribution to smoking-associated lung carcinogenesis is poorly understood. Here we show that a tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced insulin-like growth factor 1 receptor (IGF-1R) activation via β-adrenergic receptor (β-AR) is crucial for smoking-associated lung carcinogenesis. Treatment with NNK stimulated the IGF-1R signaling pathway in a time- and dose-dependent manner, which was suppressed by pharmacological or genomic blockade of β-AR and the downstream signaling including a Gβγ subunit of β-AR and phospholipase C (PLC). Consistently, β-AR agonists led to increased IGF-1R phosphorylation. The increase in IGF2 transcription via β-AR, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-kappa B (NF-κB) was associated with NNK-induced IGF-1R activation. Finally, treatment with β-AR antagonists suppressed the acquisition of transformed phenotypes in lung epithelial cells and lung tumor formation in mice. These results suggest that blocking β-AR-mediated IGF-1R activation can be an effective strategy for lung cancer prevention in smokers.

Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

PubMed Central

Kim, Seung-Jin; Choi, Hojung; Park, Sung-Soo; Chang, Chawnshang; Kim, Eungseok

2011-01-01

Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, is highly expressed in prostate cancer although the SCD protein has been known to be rapidly turned over by proteolytic cleavage. The present data demonstrate that SCD can promote proliferation of androgen receptor (AR)-positive LNCaP prostate cancer cells and enhance dihydrotestosterone (DHT)-induced AR transcriptional activity, resulting in increased expression of prostatespecific antigen (PSA) and kallikrein-related peptidase 2 (KLK2). Interestingly, among the previously reported SCDderived peptides produced by proteolytic cleavage of SCD, a peptide spanning amino acids 130-162 of SCD (SCDCoRNR) contained the CoRNR box motif (LFLII) and enhanced AR transcriptional activity. In contrast, a mutant SCD-CoRNR in which Leu136 was replaced by Ala had no effect on AR transcriptional activity. Moreover, SCDCoRNR directly interacted with AR and inhibited RIP140 suppression of AR transactivation. Knockdown of the SCD gene by SCD microRNA suppressed AR transactivation with decreased cell proliferation, suggesting that SCD may regulate the proliferation of LNCaP cells via modulation of AR transcriptional activity. Moreover, ectopic expression of SCD in LNCaP cells facilitated LNCaP tumor formation and growth in nude mice. Together, the data indicate that SCD plays a key role in the regulation of AR transcriptional activity in prostate cancer cells. PMID:21331774

Carboniferous Granitoid Magmatism of Northern Taimyr: Results of Isotopic-Geochemical Study and Geodynamic Interpretation

NASA Astrophysics Data System (ADS)

Kurapov, M. Yu.; Ershova, V. B.; Makariev, A. A.; Makarieva, E. V.; Khudoley, A. K.; Luchitskaya, M. V.; Prokopiev, A. V.

2018-03-01

Data on the petrography, geochemistry, and isotopic geochronology of granites from the northern part of the Taimyr Peninsula are considered. The Early-Middle Carboniferous age of these rocks has been established (U-Pb, SIMS). Judging by the results of 40Ar/39Ar dating, the rocks underwent metamorphism in the Middle Permian. In geochemical and isotopic composition, the granitic rocks have much in common with evolved I-type granites. This makes it possible to specify a suprasubduction marginal continental formation setting. The existence of an active Carboniferous margin along the southern edge of the Kara Block (in presentday coordinates) corroborates the close relationship of the studied region with the continent of Baltia.

Identification of the atmospheric river drivers key on local flood generating mechanism and its sensitivity under the climate change

NASA Astrophysics Data System (ADS)

Lorente-Plazas, Raquel; Mauger, Guillaume; Salathé, Eric; Mitchell, Todd P.

2017-04-01

Flooding is one of the natural hazard that causes the significant economic, ecosystem and human losses every year. Large percentage of floodings in the western of the US caused by heavy precipitation events are associated to atmospheric rivers (ARs). With the warmer climate is expected an increase of saturated water pressure which could increase the intensity and frequency of the ARs. In this work we attend to address two questions: 1) what are the large-scale drivers that promotes differences in ARs promoting heavy precipitation at different locations and 2) how climate change will influence on ARs and extreme precipitation. The methods applied in our analysis consist on a dynamical downscaling using the Weather Research and Forecasting (WRF) model. The target region is the western coastline U.S. on a domain with 12-km grid spacing. Regional climate simulations (RCM) encompass a historical period (1970-2010) and future projections (2020-2060) using NNRP and ECHAM as initial and boundary conditions. Clustering methods are applied to the RCM to identify regions with similar precipitation variability. At each region, the extreme events of precipitation according to 99 percentile are identified and associated to integrated vapor transport (ITV). Results show how heaviest precipitation in each region is associated to different AR patterns. When an AR impacts coastline, the direction and intensity of the IVT determine the areas affected by heavy precipitation. Coastal mountains play a key role intensifying the precipitation in the coastline and avoiding the inland penetration of the IVT. The shape of the atmospheric rivers is related to differences in 500 hPa geopotential between the mean and the extreme precipitation. Areas with heaviest precipitation are located in the interface of Z500 differences.

Wage and Salary Stabilization in a National Security Emergency

DTIC Science & Technology

1984-10-01

Arkansas Houston, Texas Eldorado, AR Bryan, TX Fayetteville, AR Lufkin, TX 2-8 Wage and Salary 2 - 9 . Region VI cont. Fort Smith, AR Waco, TX Jonesboro , AR ...applied to: financial and monetary systems: wages, salaries, and benefits; prices; rents; and rationing of essential goods. These measures are ...in terms of a number of conditions. They are : CONDITION I: Peacetime CONDITION II: National emergency (Threat of war) CONDITION ILIA: Mobilization

A compilation of K-Ar-ages for southern California

USGS Publications Warehouse

Miller, Fred K.; Morton, Douglas M.; Morton, Janet L.; Miller, David M.

2014-01-01

The purpose of this report is to make available a large body of conventional K-Ar ages for granitic, volcanic, and metamorphic rocks collected in southern California. Although one interpretive map is included, the report consists primarily of a systematic listing, without discussion or interpretation, of published and unpublished ages that may be of value in future regional and other geologic studies. From 1973 to 1979, 468 rock samples from southern California were collected for conventional K-Ar dating under a regional geologic mapping project of Southern California (predecessor of the Southern California Areal Mapping Project). Most samples were collected and dated between 1974 and 1977. For 61 samples (13 percent of those collected), either they were discarded for varying reasons, or the original collection data were lost. For the remaining samples, 518 conventional K-Ar ages are reported here; coexisting mineral pairs were dated from many samples. Of these K-Ar ages, 225 are previously unpublished, and identified as such in table 1. All K-Ar ages are by conventional K-Ar analysis; no 40Ar/39Ar dating was done. Subsequent to the rock samples collected in the 1970s and reported here, 33 samples were collected and 38 conventional K-Ar ages determined under projects directed at (1) characterization of the Mesozoic and Cenozoic igneous rocks in and on both sides of the Transverse Ranges and (2) clarifying the Mesozoic and Cenozoic tectonics of the eastern Mojave Desert. Although previously published (Beckerman et al., 1982), another eight samples and 11 conventional K-Ar ages are included here, because they augment those completed under the previous two projects.

Use of an audience response system (ARS) in a dual-campus classroom environment.

PubMed

Medina, Melissa S; Medina, Patrick J; Wanzer, Donald S; Wilson, Jane E; Er, Nelson; Britton, Mark L

2008-04-15

To implement an audience response system in a dual-campus classroom that aggregated data during graded (attendance and quizzes) and non-graded classroom activities (formative quizzes, case discussions, examination reviews, and team activities) and explore its strengths, weaknesses, and impact on active learning. After extensive research, an appropriate audience response system was selected and implemented in a dual-classroom setting for a third-year required PharmD course. Students were assigned a clicker and training and policies regarding clicker use were reviewed. Activities involving clicker use were carefully planned to simultaneously engage students in both classrooms in real time. Focus groups were conducted with students to gather outcomes data. Students and faculty members felt that the immediate feedback the automated response system (ARS) provided was most beneficial during non-graded activities. Student anxiety increased with use of ARS during graded activities due to fears regarding technology failure, user error, and academic integrity. ARS is a viable tool for increasing active learning in a doctor of pharmacy (PharmD) program, especially when used for non-graded class activities. Faculty members should proceed cautiously with using ARS for graded classroom activities and develop detailed and documented policies for ARS use.

Role of Complement on Broken Surfaces After Trauma.

PubMed

Huber-Lang, Markus; Ignatius, Anita; Brenner, Rolf E

2015-01-01

Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.

Accessories make the outfit: Accessory Chromosomes and other dispensable DNA regions in plant-pathogenic Fungi.

PubMed

Bertazzoni, Stefania; Williams, Angela; Jones, Darcy A B; Syme, Robert A; Tan, Kar-Chun; Hane, James Kyawzwar

2018-04-17

Fungal pathogen genomes can often be divided into core and accessory regions. Accessory regions may be comprised of either accessory regions (ARs) within core chromosomes (CCs), or wholly-dispensable (accessory) chromosomes (ACs). Fungal ACs and ARs typically accumulate mutations and structural rearrangements more rapidly over time than CCs, and many harbour genes relevant to host-pathogen interactions. These regions are of particular interest in plant pathology and include host-specific virulence factors and secondary metabolite synthesis gene clusters. This review outlines known ACs and ARs in fungal genomes, methods used for their detection, their common properties that differentiate them from the core genome, and what is currently known of their various roles in pathogenicity. Reports on the evolutionary processes generating and shaping AC/AR compartments are discussed, including repeat induced point mutation (RIP) and breakage-fusion-bridge (BFB) cycles. Previously ACs have been studied extensively within key genera including Fusarium, Zymoseptoria and Alternaria, but are growing in their frequency of observation and perceived importance across a wider range of fungal species. Recent advances in sequencing technologies permit affordable genome assembly and re-sequencing of populations that will facilitate further discovery and routine screening of ACs.

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

Alizarin Red S-Confined Layer-By-Layer Films as Redox-Active Coatings on Electrodes for the Voltammetric Determination of L-Dopa

PubMed Central

Takahashi, Shigehiro; Suzuki, Iwao; Sugawara, Tatsuro; Seno, Masaru; Minaki, Daichi; Anzai, Jun-Ichi

2017-01-01

The preparation of redox-active coatings is a key step in fabricating electrochemical biosensors. To this goal, a variety of coating materials have been used in combination with redox-active compounds. In this study, alizarin red S (ARS) was confined in layer-by-layer (LbL) films composed of poly(ethyleneimine) (PEI) and carboxymethylcellulose (CMC) to study the redox properties. A gold (Au) disc electrode coated with PEI/CMC LbL film was immersed in an ARS solution to uptake ARS into the film. ARS was successfully confined in the LbL film through electrostatic interactions. The cyclic voltammogram (CV) of ARS-confined PEI/CMC film-coated electrodes thus prepared exhibited redox waves in the potential range from −0.5 to −0.7 V originating from 9,10-anthraquinone moiety in ARS, demonstrating that ARS preserves its redox activity in the LbL film. An additional oxidation peak appeared around −0.4 V in the CV recorded in the solution containing phenylboronic acid (PBA), due to the formation of a boronate ester of ARS (ARS-PBA) in the film. The oxidation peak current at −0.4 V decreased upon addition of 3,4-dihydroxyphenylalanine (L-dopa) to the solution. Thus, the results suggest a potential use of the ARS-confined PEI/CMC films for constructing voltammetric sensors for L-dopa. PMID:28772942

Androgen Receptor Antagonism By Divalent Ethisterone Conjugates In Castrate-Resistant Prostate Cancer Cells

PubMed Central

Levine, Paul M.; Lee, Eugine; Greenfield, Alex; Bonneau, Richard; Logan, Susan K.; Garabedian, Michael J.; Kirshenbaum, Kent

2013-01-01

Sustained treatment of prostate cancer with Androgen Receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, new therapeutic regimens that target and modulate AR activity could prove beneficial. We previously introduced a versatile chemical platform to generate competitive and non-competitive multivalent peptoid oligomer conjugates that modulate AR activity. In particular, we identified a linear and a cyclic divalent ethisterone conjugate that exhibit potent anti-proliferative properties in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we characterize the mechanism of action of these compounds utilizing confocal microscopy, time-resolved fluorescence resonance energy transfer, chromatin immunoprecipitation, flow cytometry, and microarray analysis. The linear conjugate competitively blocks AR action by inhibiting DNA binding. In addition, the linear conjugate does not promote AR nuclear localization or co-activator binding. In contrast, the cyclic conjugate promotes AR nuclear localization and induces cell-cycle arrest, despite its inability to compete against endogenous ligand for binding to AR in vitro. Genome-wide expression analysis reveals that gene transcripts are differentially affected by treatment with the linear or cyclic conjugate. Although the divalent ethisterone conjugates share extensive chemical similarities, we illustrate that they can antagonize the AR via distinct mechanisms of action, establishing new therapeutic strategies for potential applications in AR pharmacology. PMID:22871957

Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents.

PubMed

Lu, Junxuan; Kim, Sung-Hoon; Jiang, Cheng; Lee, HyoJeong; Guo, Junming

2007-09-01

Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for PCa and has serious toxic sideeffects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of PCa. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakai (Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5alpha-dihydrotestesterone to AR and increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the "pure" anti-androgen bicalutamide and is more potent than bicalutamide in inducing PCa apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomer decursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-androgen/ AR agents from complex herbal mixtures.

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified aromatic-turmerone (AR).

PubMed

Yonggang, Tan; Yiming, Meng; Heying, Zhang; Cheng, Sun; Qiushi, Wang; Xianghong, Yang; Wei, Zheng; Huawei, Zhou; Shan, Fengping

2012-10-01

The aim of this work is to evaluate the effects of purified aromatic-turmerone (ar-turmerione, AR) on murine dendritic cells (DCs). These impacts of AR on DCs from bone marrow derived DCs(BMDCs) were assessed with use of conventional scanning electron microscopy (SEM), fluorescence activated cell sorting (FACS), transmission electron microscopy (TEM), cytochemistry assay, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We found that AR induced phenotypic maturation as evidenced by increased expression of CD86, CD40, CD83, CD80 and major histocompatibility complex II (MHC II). The functional tests showed the activity of acidic phosphatase (ACP) inside the DCs were downregulated after treatment with AR (which occurs when phagocytosis of DCs were decreased). Finally, we proved that AR increased the production of IL-12 and tumor necrosis factor α (TNF-α). These data suggested that AR could promote phenotypic and functional maturation of DCs and this adjuvant-like activity may have potential therapeutic value. It is therefore concluded that AR could exert positive modulation on murine DCs.

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified Aromatic-Turmerone (AR)

PubMed Central

Yonggang, Tan; Yiming, Meng; Heying, Zhang; Cheng, Sun; Qiushi, Wang; Xianghong, Yang; Wei, Zheng; Huawei, Zhou; Shan, Fengping

2012-01-01

The aim of this work is to evaluate the effects of purified aromatic-turmerone(ar-turmerione, AR) on murine dendritic cells (DCs). These impacts of AR on DCs from bone marrow derived DCs(BMDCs) were assessed with use of conventional scanning electron microscopy (SEM), fluorescence activated cell sorting (FACS), transmission electron microscopy (TEM), cytochemistry assay, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We found that AR induced phenotypic maturation as evidenced by increased expression of CD86, CD40, CD83, CD80 and major histocompatibility complex II (MHC II). The functional tests showed the activity of acidic phosphatase (ACP) inside the DCs were downregulated after treatment with AR (which occurs when phagocytosis of DCs were decreased). Finally, we proved that AR increased the production of IL-12 and tumor necrosis factor α (TNF-α). These data suggested that AR could promote phenotypic and functional maturation of DCs and this adjuvant-like activity may have potential therapeutic value. It is therefore concluded that AR could exert positive modulation on murine DCs. PMID:23095866

The Hsp90 Inhibitor, 17-AAG, Prevents the Ligand-Independent Nuclear Localization of Androgen Receptor in Refractory Prostate Cancer Cells

PubMed Central

Saporita, Anthony J.; Ai, Junkui; Wang, Zhou

2010-01-01

BACKGROUND Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgen-refractory prostate cancer cells. METHODS AND RESULTS We demonstrate increased nuclear localization of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells compared to parental androgen-sensitive human prostate cancer LNCaP cells. Analysis of AR mutants impaired in ligand-binding indicates that the nuclear localization of AR in C4-2 cells is truly androgen-independent. The hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA expression and disrupts the ligand-independent nuclear localization of AR at doses much lower than required to inhibit androgen-induced nuclear import. CONCLUSIONS Hsp90 is a key regulator of ligand-independent nuclear localization and activation of AR in androgen-refractory prostate cancer cells. PMID:17221841

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

PubMed

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-08

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure

PubMed Central

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-01

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways. PMID:25567365

Selective inactivation of adenosine A2A receptors in striatal neurons enhances working memory and reversal learning

PubMed Central

Wei, Catherine J.; Singer, Philipp; Coelho, Joana; Boison, Detlev; Feldon, Joram; Yee, Benjamin K.; Chen, Jiang-Fan

2011-01-01

The adenosine A2A receptor (A2AR) is highly enriched in the striatum where it is uniquely positioned to integrate dopaminergic, glutamatergic, and other signals to modulate cognition. Although previous studies support the hypothesis that A2AR inactivation can be pro-cognitive, analyses of A2AR's effects on cognitive functions have been restricted to a small subset of cognitive domains. Furthermore, the relative contribution of A2ARs in distinct brain regions remains largely unknown. Here, we studied the regulation of multiple memory processes by brain region-specific populations of A2ARs. Specifically, we evaluated the cognitive impacts of conditional A2AR deletion restricted to either the entire forebrain (i.e., cerebral cortex, hippocampus, and striatum, fb-A2AR KO) or to striatum alone (st-A2AR KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A2AR-dependent signaling in either the entire forebrain or striatum alone is associated with two specific phenotypes indicative of cognitive flexibility—enhanced working memory and enhanced reversal learning. These selective pro-cognitive phenotypes seemed largely attributed to inactivation of striatal A2ARs as they were captured by A2AR deletion restricted to striatal neurons. Neither spatial reference memory acquisition nor spatial recognition memory were grossly affected, and no evidence for compensatory changes in striatal or cortical D1, D2, or A1 receptor expression was found. This study provides the first direct demonstration that targeting striatal A2ARs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions. PMID:21693634

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

PubMed

Wang, X-Y; Ma, T-T; Wang, X-Y; Zhuang, Y; Wang, X-D; Ning, H-Y; Shi, H-Y; Yu, R-L; Yan, D; Huang, H-D; Bai, Y-F; Shan, G-L; Zhang, B; Song, Q-K; Zhang, Y-F; Zhang, T-J; Jia, D-Z; Liu, X-L; Kang, Z-X; Yan, W-J; Yang, B-T; Bao, X-Z; Sun, S-H; Zhang, F-F; Yu, W-H; Bai, C-L; Wei, T; Yang, T; Ma, T-Q; Wu, X-B; Liu, J-G; Du, H; Zhang, L; Yan, Y; Wang, D-Y

2018-06-01

The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions. © 2018 The Authors. Allergy Published by John Wiley and Sons Ltd.

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

Occurrence and potential causes of androgenic activities in source and drinking water in China.

PubMed

Hu, Xinxin; Shi, Wei; Wei, Si; Zhang, Xiaowei; Feng, Jianfang; Hu, Guanjiu; Chen, Sulan; Giesy, John P; Yu, Hongxia

2013-09-17

The increased incidences of disorders of male reproductive tract as well as testicular and prostate cancers have been attributed to androgenic pollutants in the environment. Drinking water is one pathway of exposure through which humans can be exposed. In this study, both potencies of androgen receptor (AR) agonists and antagonists were determined in organic extracts of raw source water as well as finished water from waterworks, tap water, boiled water, and poured boiled water in eastern China. Ten of 13 samples of source water exhibited detectable AR antagonistic potencies with AR antagonist equivalents (Ant-AR-EQs) ranging from <15.3 (detection limit) to 140 μg flutamide/L. However, no AR agonistic activity was detected in any source water. All finished water from waterworks, tap water, boiled water, and poured boiled water exhibited neither AR agonistic nor antagonistic activity. Although potential risks are posed by source water, water treatment processes effectively removed AR antagonists. Boiling and pouring of water further removed these pollutants. Phthalate esters (PAEs) including diisobutyl phthalate (DIBP) and dibutyl phthalate (DBP) were identified as major contributors to AR antagonistic potencies in source waters. Metabolites of PAEs exhibited no AR antagonistic activity and did not increase potencies of PAEs when they coexist.

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

Understanding the conformation transition in the activation pathway of β2 adrenergic receptor via a targeted molecular dynamics simulation.

PubMed

Xiao, Xiuchan; Zeng, Xiaojun; Yuan, Yuan; Gao, Nan; Guo, Yanzhi; Pu, Xuemei; Li, Menglong

2015-01-28

G protein coupled receptors (GPCRs) play a crucial role in regulating signal recognition and transduction through their activation. The conformation transition in the activation pathway is of particular importance for their function. However, it has been poorly elucidated due to experimental difficulties in determining the conformations and the time limitation of conventional molecular dynamics (CMD) simulation. Thus, in this work, we employed a targeted molecular dynamic (TMD) simulation to study the activation process from an inactive structure to a fully active one for β2 adrenergic receptor (β2AR). As a reference, 110 ns CMD simulations on wild β2AR and its D130N mutant were also carried out. TMD results show that there is at least an intermediate conformation cluster in the activation process, evidenced by the principal component analysis and the structural and dynamic differences of some important motifs. It is noteworthy that the activation of the ligand binding site lags the G-protein binding site, displaying uncoupled correlation. Comparisons between the CMD and TMD results show that the D130N mutation significantly speeds up ICL2 and key ionic lock to enter into the intermediate state, which to some extent facilitates the activation involved in the NPxxY, DRY region and the separation between TM3 and TM6. However, the contribution from the D130N mutation to the activation of the ligand binding site could not be observed within the scale of 110 ns time. These observations could provide novel insights into previous studies for better understanding of the activation mechanism for β2AR.

Thermostabilization of the β1-adrenergic receptor correlates with increased entropy of the inactive state.

PubMed

Niesen, Michiel J M; Bhattacharya, Supriyo; Grisshammer, Reinhard; Tate, Christopher G; Vaidehi, Nagarajan

2013-06-20

The dynamic nature of GPCRs is a major hurdle in their purification and crystallization. Thermostabilization can facilitate GPCR structure determination, as has been shown by the structure of the thermostabilized β1-adrenergic receptor (β1AR) mutant, m23-β1AR, which has been thermostabilized in the inactive state. However, it is unclear from the structure how the six thermostabilizing mutations in m23-β1AR affect receptor dynamics. We have used molecular dynamics simulations in explicit solvent to compare the conformational ensembles for both wild type β1AR (wt-β1AR) and m23-β1AR. Thermostabilization results in an increase in the number of accessible microscopic conformational states within the inactive state ensemble, effectively increasing the side chain entropy of the inactive state at room temperature, while suppressing large-scale main chain conformational changes that lead to activation. We identified several diverse mechanisms of thermostabilization upon mutation. These include decrease of long-range correlated movement between residues in the G-protein coupling site to the extracellular region (Y227A(5.58), F338M(7.48)), formation of new hydrogen bonds (R68S), and reduction of local stress (Y227(5.58), F327(7.37), and F338(7.48)). This study provides insights into microscopic mechanisms underlying thermostability that leads to an understanding of the effect of these mutations on the structure of the receptor.

The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

PubMed

Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

2018-03-01

In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

PubMed

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

A HELIOSEISMIC SURVEY OF NEAR-SURFACE FLOWS AROUND ACTIVE REGIONS AND THEIR ASSOCIATION WITH FLARES

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

Braun, D. C., E-mail: dbraun@cora.nwra.com

We use helioseismic holography to study the association of shallow flows with solar flare activity in about 250 large sunspot groups observed between 2010 and 2014 with the Helioseismic and Magnetic Imager on the Solar Dynamics Observatory. Four basic flow parameters: horizontal speed, horizontal component of divergence, vertical component of vorticity, and a vertical kinetic helicity proxy, are mapped for each active region (AR) during its passage across the solar disk. Flow indices are derived representing the mean and standard deviation of these parameters over magnetic masks and compared with contemporary measures of flare X-ray flux. A correlation exists formore » several of the flow indices, especially those based on the speed and the standard deviation of all flow parameters. However, their correlation with X-ray flux is similar to that observed with the mean unsigned magnetic flux density over the same masks. The temporal variation of the flow indices are studied, and a superposed epoch analysis with respect to the occurrence to 70 M and X-class flares is made. While flows evolve with the passage of the ARs across the disk, no discernible precursors or other temporal changes specifically associated with flares are detected.« less

c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.

PubMed

Barfeld, Stefan J; Urbanucci, Alfonso; Itkonen, Harri M; Fazli, Ladan; Hicks, Jessica L; Thiede, Bernd; Rennie, Paul S; Yegnasubramanian, Srinivasan; DeMarzo, Angelo M; Mills, Ian G

2017-04-01

Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa. Its impact on AR activity, however, remains elusive. In this study, we assessed the impact of c-Myc overexpression on AR activity and transcriptional output in a PCa cell line model and validated the antagonistic effect of c-MYC on AR-targets in patient samples. We found that c-Myc overexpression partially reprogrammed AR chromatin occupancy and was associated with altered histone marks distribution, most notably H3K4me1 and H3K27me3. We found c-Myc and the AR co-occupy a substantial number of binding sites and these exhibited enhancer-like characteristics. Interestingly, c-Myc overexpression antagonised clinically relevant AR target genes. Therefore, as an example, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 (alias PSA, prostate specific antigen), and Glycine N-Methyltransferase (GNMT), in patient samples. Our findings provide unbiased evidence that MYC overexpression deregulates the AR transcriptional program, which is thought to be a driving force in PCa. Crown Copyright © 2017. Published by Elsevier B.V. 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.

Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated ARser81

PubMed Central

Mehraein-Ghomi, Farideh; Church, Dawn R.; Schreiber, Cynthia L.; Weichmann, Ashley M.; Basu, Hirak S.; Wilding, George

2015-01-01

Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21WAF/CIP1, which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21WAF/CIP1, since p21WAF/CIP1 is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth. PMID:26622945

Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP.

PubMed

Sarkar, Sukumar; Brautigan, David L; Larner, James M

2017-08-01

Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. Aurora A kinase is activated by 2-ME in the S-phase as well as during mitosis, and phosphorylates CHIP at S273. Prostate cancer cells expressing an S273A mutant of CHIP have attenuated AR degradation upon 2-ME treatment compared with cells expressing wild-type CHIP, supporting the idea that CHIP phosphorylation by Aurora A activates its E3 ligase activity for the AR. These results reveal a novel 2-ME→Aurora A→CHIP→AR pathway that promotes AR degradation via the proteasome that may offer novel therapeutic opportunities for prostate cancer. Mol Cancer Res; 15(8); 1063-72. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

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

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

Investigation of relationships between parameters of solar nano-flares and solar activity

NASA Astrophysics Data System (ADS)

Safari, Hossein; Javaherian, Mohsen; Kaki, Bardia

2016-07-01

Solar flares are one of the important coronal events which are originated in solar magnetic activity. They release lots of energy during the interstellar medium, right after the trigger. Flare prediction can play main role in avoiding eventual damages on the Earth. Here, to interpret solar large-scale events (e.g., flares), we investigate relationships between small-scale events (nano-flares) and large-scale events (e.g., flares). In our method, by using simulations of nano-flares based on Monte Carlo method, the intensity time series of nano-flares are simulated. Then, the solar full disk images taken at 171 angstrom recorded by SDO/AIA are employed. Some parts of the solar disk (quiet Sun (QS), coronal holes (CHs), and active regions (ARs)) are cropped and the time series of these regions are extracted. To compare the simulated intensity time series of nano-flares with the intensity time series of real data extracted from different parts of the Sun, the artificial neural networks is employed. Therefore, we are able to extract physical parameters of nano-flares like both kick and decay rate lifetime, and the power of their power-law distributions. The procedure of variations in the power value of power-law distributions within QS, CH is similar to AR. Thus, by observing the small part of the Sun, we can follow the procedure of solar activity.

The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

DTIC Science & Technology

2012-10-01

support with our hypothesis, expressions of AR co-repressors (48-50), HDAC1, HDAC3 or SirT1 inhibit the ligand-induced AR activation at different...signaling and androgen-dependent growth. We hypothesis that DACH1/Six1/Eya pathway is an endogenous regulator of AR trans- activation and contributes to...mechanism. Inhibitory function of Eya1 on AR transactivation required a phosphates activity and could be enhanced by ectopic expression of co-repressors

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.

ASYMMETRY OF HELICITY INJECTION FLUX IN EMERGING ACTIVE REGIONS

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

Tian Lirong; Alexander, David

Observational and modeling results indicate that typically the leading magnetic field of bipolar active regions (ARs) is often spatially more compact, while more dispersed and fragmented in following polarity. In this paper, we address the origin of this morphological asymmetry, which is not well understood. Although it may be assumed that, in an emerging {omega}-shaped flux tube, those portions of the flux tube in which the magnetic field has a higher twist may maintain its coherence more readily, this has not been tested observationally. To assess this possibility, it is important to characterize the nature of the fragmentation and asymmetrymore » in solar ARs and this provides the motivation for this paper. We separately calculate the distribution of the helicity flux injected in the leading and following polarities of 15 emerging bipolar ARs, using the Michelson Doppler Image 96 minute line-of-sight magnetograms and a local correlation tracking technique. We find from this statistical study that the leading (compact) polarity injects several times more helicity flux than the following (fragmented) one (typically 3-10 times). This result suggests that the leading polarity of the {omega}-shaped flux tube possesses a much larger amount of twist than the following field prior to emergence. We argue that the helicity asymmetry between the leading and following magnetic field for the ARs studied here results in the observed magnetic field asymmetry of the two polarities due to an imbalance in the magnetic tension of the emerging flux tube. We suggest that the observed imbalance in the helicity distribution results from a difference in the speed of emergence between the leading and following legs of an inclined {omega}-shaped flux tube. In addition, there is also the effect of magnetic flux imbalance between the two polarities with the fragmented following polarity displaying spatial fluctuation in both the magnitude and sign of helicity measured.« less

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2014 CFR

2014-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2013 CFR

2013-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2012 CFR

2012-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements.

PubMed

Takai, Hideki; Nakayama, Youhei; Kim, Dong-Soon; Arai, Masato; Araki, Shouta; Mezawa, Masaru; Nakajima, Yu; Kato, Naoko; Masunaga, Hiroshi; Ogata, Yorimasa

2007-09-01

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. Androgens are steroid hormones that are essential for skeletal development. The androgen receptor (AR) is a transcription factor and a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. To determine the molecular mechanism involved in the stimulation of bone formation, we have analyzed the effects of androgens and AR effects on BSP gene transcription. AR protein levels were increased after AR overexpression in ROS17/2.8 cells. BSP mRNA levels were increased by AR overexpression. However, the endogenous and overexpressed BSP mRNA levels were not changed by DHT (10(-8) M, 24 h). Whereas luciferase (LUC) activities in all constructs, including a short construct (nts -116 to +60), were increased by AR overexpression, the basal and LUC activities enhanced by AR overexpression were not induced by DHT (10(-8)M, 24 h). The effect of AR overexpression was abrogated by 2 bp mutations in either the cAMP response element (CRE) or activator protein 1 (AP1)/glucocorticoid response element (GRE). Gel shift analyses showed that AR overexpression increased binding to the CRE and AP1/GRE elements. Notably, the CRE-protein complexes were supershifted by phospho-CREB antibody, and CREB, c-Fos, c-Jun, and AR antibodies disrupted the complexes formation. The AP1/GRE-protein complexes were supershifted by c-Fos antibody and c-Jun, and AR antibodies disrupted the complexes formation. These studies demonstrate that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene.

StAR Enhances Transcription of Genes Encoding the Mitochondrial Proteases Involved in Its Own Degradation

PubMed Central

Bahat, Assaf; Perlberg, Shira; Melamed-Book, Naomi; Lauria, Ines; Langer, Thomas

2014-01-01

Steroidogenic acute regulatory protein (StAR) is essential for steroid hormone synthesis in the adrenal cortex and the gonads. StAR activity facilitates the supply of cholesterol substrate into the inner mitochondrial membranes where conversion of the sterol to a steroid is catalyzed. Mitochondrial import terminates the cholesterol mobilization activity of StAR and leads to mounting accumulation of StAR in the mitochondrial matrix. Our studies suggest that to prevent mitochondrial impairment, StAR proteolysis is executed by at least 2 mitochondrial proteases, ie, the matrix LON protease and the inner membrane complexes of the metalloproteases AFG3L2 and AFG3L2:SPG7/paraplegin. Gonadotropin administration to prepubertal rats stimulated ovarian follicular development associated with increased expression of the mitochondrial protein quality control system. In addition, enrichment of LON and AFG3L2 is evident in StAR-expressing ovarian cells examined by confocal microscopy. Furthermore, reporter studies of the protease promoters examined in the heterologous cell model suggest that StAR expression stimulates up to a 3.5-fold increase in the protease gene transcription. Such effects are StAR-specific, are independent of StAR activity, and failed to occur upon expression of StAR mutants that do not enter the matrix. Taken together, the results of this study suggest the presence of a novel regulatory loop, whereby acute accumulation of an apparent nuisance protein in the matrix provokes a mitochondria to nucleus signaling that, in turn, activates selected transcription of genes encoding the enrichment of mitochondrial proteases relevant for enhanced clearance of StAR. PMID:24422629

Evidence of suppressed heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Winebarger, Amy R.; Panesar, Navdeep K.; Moore, Ronald

2015-04-01

Observations of active region (AR) coronae in different EUV wavelengths reveal the presence of various loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect opposite-polarity plage or a sunspot to a opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94 A, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.From this result, we further hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbrae. Many transient, outstandingly bright, loops in the AIA 94 A movie of the AR do have this expected rooting pattern.

Two DNA-binding factors recognize specific sequences at silencers, upstream activating sequences, autonomously replicating sequences, and telomeres in Saccharomyces cerevisiae

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

Buchman, A.R.; Kimmerly, W.J.; Rine, J.

1988-01-01

Two DNA-binding factors from Saccharomyces cerevisiae have been characterized, GRFI (general regulatory factor I) and ABFI (ARS-binding factor I), that recognize specific sequences within diverse genetic elements. GRFI bound to sequences at the negative regulatory elements (silencers) of the silent mating type loci HML E and HMR E and to the upstream activating sequence (UAS) required for transcription of the MAT ..cap alpha.. genes. A putative conserved UAS located at genes involved in translation (RPG box) was also recognized by GRFI. In addition, GRFI bound with high affinity to sequences within the (C/sub 1-3/A)-repeat region at yeast telomeres. Binding sitesmore » for GRFI with the highest affinity appeared to be of the form 5'-(A/G)(A/C)ACCCAN NCA(T/C)(T/C)-3', where N is any nucleotide. ABFI-binding sites were located next to autonomously replicating sequences (ARSs) at controlling elements of the silent mating type loci HMR E, HMR I, and HML I and were associated with ARS1, ARS2, and the 2..mu..m plasmid ARS. Two tandem ABFI binding sites were found between the HIS3 and DED1 genes, several kilobase pairs from any ARS, indicating that ABFI-binding sites are not restricted to ARSs. The sequences recognized by AFBI showed partial dyad-symmetry and appeared to be variations of the consensus 5'-TATCATTNNNNACGA-3'. GRFI and ABFI were both abundant DNA-binding factors and did not appear to be encoded by the SIR genes, whose product are required for repression of the silent mating type loci. Together, these results indicate that both GRFI and ABFI play multiple roles within the cell.« less

The relationship between the change of magnetic energy and eruption behavior in NOAA AR 11429

NASA Astrophysics Data System (ADS)

Wang, R.; Liu, Y. D.

2013-12-01

We study the evolution of magnetic energy in an active region (AR) NOAA 11429, which produced a series of X/M class flares and fast coronal mass ejections (CMEs) in March 2012. In particular, this AR spawned double X-class flares (X5.4/X1.3) within a time internal of only 1 hr on March 7, which are associated with wide and fast CMEs with speeds of ~2000 km/s. A nonlinear force-free field extrapolation method is adopted to reconstruct the coronal magnetic field. We apply this method to a time series of 176 high-cadence vector magnetograms of the AR acquired by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory (HMI/SDO), which span a time interval of 1.5 days. We investigate the budgets of the free magnetic energy and relative magnetic helicity. We find that there exist some relations between the changes of magnetic energy and flare magnitudes. Compared with previous studies, our results indicate that the magnetic energy decrease occurs before the flare and CME launch time. We will also combine images from the Atmospheric Imaging Assembly (AIA) to further explore the detailed process of the eruptions.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells

PubMed Central

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

Background: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. Objective: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Materials and Methods: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. Results: TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Conclusion: Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. SUMMARY Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein PMID:28216900

Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection.

PubMed

Hu, Rong; Chen, Juan; Lujan, Brendan; Lei, Ruixue; Zhang, Mi; Wang, Zefen; Liao, Mingxia; Li, Zhiqiang; Wan, Yu; Liu, Fang; Feng, Hua; Wan, Qi

2016-10-03

Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The effect of glycine on Akt activation is sensitive to the antagonist of glycine-GluN1 binding site. As a functional consequence, glycine protects against excitotoxicity-induced neuronal death through the non-ionotropic activity of GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus, this study reveals an unexpected role of glycine in eliciting a non-ionotropic activity of GluN2ARs to confer neuroprotection via Akt activation.

Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection

PubMed Central

Hu, Rong; Chen, Juan; Lujan, Brendan; Lei, Ruixue; Zhang, Mi; Wang, Zefen; Liao, Mingxia; Li, Zhiqiang; Wan, Yu; Liu, Fang; Feng, Hua; Wan, Qi

2016-01-01

Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The effect of glycine on Akt activation is sensitive to the antagonist of glycine-GluN1 binding site. As a functional consequence, glycine protects against excitotoxicity-induced neuronal death through the non-ionotropic activity of GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus, this study reveals an unexpected role of glycine in eliciting a non-ionotropic activity of GluN2ARs to confer neuroprotection via Akt activation. PMID:27694970

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.

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

Foraging destinations and marine habitat use of short-tailed albatrosses: A multi-scale approach using first-passage time analysis

USGS Publications Warehouse

Suryan, R.M.; Sato, F.; Balogh, G.R.; David, Hyrenbach K.; Sievert, P.R.; Ozaki, K.

2006-01-01

We used satellite telemetry, remotely sensed data (bathymetry, chlorophyll a (chl a), sea-surface temperature (SST), wind speed) and first-passage time (FPT) analysis to determine the distribution, movement patterns, and habitat associations of short-tailed albatrosses (Phoebastria albatrus) during the non-breeding season, 2002 and 2003. Satellite transmitters were deployed on birds immediately prior to their departure from a breeding colony at Torishima, Japan (n = 11), or at-sea in the Aleutian Islands (n = 3). Tracking durations ranged from 51 to 138 days for a total of 6709 locations after filtering (131 - 808 per bird). FPT (time required to transit a circle of given radius) revealed the location and spatial scale of area-restricted search (ARS) patterns along flight paths. On average, ARS occurred within 70 km radii. Consequently, the fit of the habitat use models increased at spatial scales beyond a 40 km FPT radius (R2 = 0.31) and stabilized for scales of 70 km and larger (R2=0.40- 0.51). At all scales, wind speed, depth or depth gradient, and chl a or chl a gradient had a significant effect on FPT (i.e., residence time). FPT increased within regions of higher gradients of depth and chl a. In contrast, FPT decreased within regions of greater depth and wind speed, with a significant interaction of wind speed and depth at some scales. Sea-surface temperature or its interactions were only significant at large spatial scales (???160 km FPT radius). Albatrosses engaged in ARS activities primarily over the shelf break and slope, including Kuroshio and Oyashio regions off the western subarctic gyre. Occasionally, birds transited the northern boundary of the Kuroshio Extension while in-route to the Aleutian Islands and Bering Sea, but overall spent little time in the western gyre. In the Aleutian Islands, ARS occurred within straits, particularly along the central and western part of the archipelago. In the Bering Sea, ARS occurred along the northern continental shelf break, the Kamchatka Current region, and east of the Commander Islands. Non-breeding short-tailed albatross concentrate foraging in oceanic areas characterized by gradients in topography and water column productivity. This study provides an understanding of the foraging ecology for a highly migratory, imperiled seabird, and confirms the importance of shelf break and slope regions as hot spots for a variety of top marine predators in the North Pacific.

76 FR 27622 - Approval and Promulgation of State Implementation Plan Revisions; Infrastructure Requirements for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-12

...), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver, Colorado 80202-1129. Hand Delivery: Director, Air Program, Environmental Protection Agency (EPA), Region 8, Mail Code 8P-AR, 1595 Wynkoop Street, Denver..., Denver, Colorado 80202-1129. EPA requests that if at all possible, you contact the individual listed in...

The Ar-NO van der Waals complex studied by resonant multiphoton ionization spectroscopy involving photoion and photoelectron measurements

NASA Astrophysics Data System (ADS)

Sato, Kenji; Achiba, Yohji; Kimura, Katsumi

1984-07-01

Using a 5% mixture of NO in Ar in a supersonic free jet, in the present work we have carried out measurements of the total ion current in the 380-385 nm laser wavelength region. We have also measured photoelectron kinetic energy spectra at individual ion current peaks. In the ion-current spectrum we have observed a new vibrational progression which consists of four peaks in the wavelength region longer than the peak of the two-photon transition of the free NO molecule NO(X, v″=0) →2hν NO(C,v'=0). It has been concluded that the new ion-current peaks are attributed to bound-to-bound transitions of the Ar-NO van der Waals complex from its ground state to the two-photon resonant state expressed by Ar-NO*(C 2Π, v'=0), in which the NO component is in the 3p Rydberg state. The whole resonant ionization process studied may be expressed by Ar-NO(X, v″=0) →2hνAr-NO*(C, v'=0) →hν Ar-NO+(X, v+=0). Each ion-current peak separation is about 50 cm-1, which may correspond to the frequency of the Ar-NO intermolecular stretching vibration, showing a strong anharmonicity. The dissociation energy (D0) of the Ar-NO*(C 2Π) state has been found to be 0.055±0.001 eV. From the photoelectron spectra, we also conclude that the adiabatic ionization energy of Ar-NO is Ia =9.148±0.005 eV and the dissociation energy of the Ar-NO+(X 1Σ) ion is D0=0.129±0.005 eV.

Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning.

PubMed

Wei, Catherine J; Singer, Philipp; Coelho, Joana; Boison, Detlev; Feldon, Joram; Yee, Benjamin K; Chen, Jiang-Fan

2011-01-01

The adenosine A(2A) receptor (A(2A)R) is highly enriched in the striatum where it is uniquely positioned to integrate dopaminergic, glutamatergic, and other signals to modulate cognition. Although previous studies support the hypothesis that A(2A)R inactivation can be pro-cognitive, analyses of A(2A)R's effects on cognitive functions have been restricted to a small subset of cognitive domains. Furthermore, the relative contribution of A(2A)Rs in distinct brain regions remains largely unknown. Here, we studied the regulation of multiple memory processes by brain region-specific populations of A(2A)Rs. Specifically, we evaluated the cognitive impacts of conditional A(2A)R deletion restricted to either the entire forebrain (i.e., cerebral cortex, hippocampus, and striatum, fb-A(2A)R KO) or to striatum alone (st-A(2A)R KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A(2A)R-dependent signaling in either the entire forebrain or striatum alone is associated with two specific phenotypes indicative of cognitive flexibility-enhanced working memory and enhanced reversal learning. These selective pro-cognitive phenotypes seemed largely attributed to inactivation of striatal A(2A)Rs as they were captured by A(2A)R deletion restricted to striatal neurons. Neither spatial reference memory acquisition nor spatial recognition memory were grossly affected, and no evidence for compensatory changes in striatal or cortical D(1), D(2), or A(1) receptor expression was found. This study provides the first direct demonstration that targeting striatal A(2A)Rs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions.

Use of an Audience Response System (ARS) in a Dual-Campus Classroom Environment

PubMed Central

Medina, Patrick J; Wanzer, Donald S; Wilson, Jane E; Er, Nelson; Britton, Mark L

2008-01-01

Objectives To implement an audience response system in a dual-campus classroom that aggregated data during graded (attendance and quizzes) and non-graded classroom activities (formative quizzes, case discussions, examination reviews, and team activities) and explore its strengths, weaknesses, and impact on active learning. Design After extensive research, an appropriate audience response system was selected and implemented in a dual-classroom setting for a third-year required PharmD course. Students were assigned a clicker and training and policies regarding clicker use were reviewed. Activities involving clicker use were carefully planned to simultaneously engage students in both classrooms in real time. Focus groups were conducted with students to gather outcomes data. Assessment Students and faculty members felt that the immediate feedback the automated response system (ARS) provided was most beneficial during non-graded activities. Student anxiety increased with use of ARS during graded activities due to fears regarding technology failure, user error, and academic integrity. Summary ARS is a viable tool for increasing active learning in a doctor of pharmacy (PharmD) program, especially when used for non-graded class activities. Faculty members should proceed cautiously with using ARS for graded classroom activities and develop detailed and documented policies for ARS use. PMID:18483604

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 ESTIMATE OF THE DETECTABILITY OF RISING FLUX TUBES

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

Birch, A. C.; Braun, D. C.; Fan, Y., E-mail: aaronb@cora.nwra.co

The physics of the formation of magnetic active regions (ARs) is one of the most important problems in solar physics. One main class of theories suggests that ARs are the result of magnetic flux that rises from the tachocline. Time-distance helioseismology, which is based on measurements of wave propagation, promises to allow the study of the subsurface behavior of this magnetic flux. Here, we use a model for a buoyant magnetic flux concentration together with the ray approximation to show that the dominant effect on the wave propagation is expected to be from the roughly 100 m s{sup -1} retrogrademore » flow associated with the rising flux. Using a B-spline-based method for carrying out inversions of wave travel times for flows in spherical geometry, we show that at 3 days before emergence the detection of this retrograde flow at a depth of 30 Mm should be possible with a signal-to-noise level of about 8 with a sample of 150 emerging ARs.« less

Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cells.

PubMed

Kizu, Ryoichi; Okamura, Kazumasa; Toriba, Akira; Mizokami, Atsushi; Burnstein, Kerry L; Klinge, Carolyn M; Hayakawa, Kazuichi

2003-12-01

We collected diesel exhaust particles (DEPs) emitted from three diesel-engine vehicles--a car, a bus, and a truck--in daily use, and prepared DEP extracts (DEPEs), designated as EC, EB, or ET, respectively. The androgenic and antiandrogenic effects of the DEPE samples were examined by a luciferase reporter assay in human prostate carcinoma PC3/AR cells transiently transfected with a prostate specific antigen gene promoter-driven luciferase expression vector pGLPSA5.8. PC3/AR is a subline of human prostate carcinoma PC3 transformed to stably express wild-type human androgen receptor (AR). While DEPE samples did not exhibit any androgenic effect, they exerted antiandrogenic effect, inhibiting dihydrotestosterone (10 pM) -induced luciferase activity by 24 to 52% at an extract concentration of 10 microg/ml. The antiandrogenic effect was greater in the following order: ET > EB > EC. Co-treatment of PC3/AR cells with SKF-525A, a nonselective inhibitor of cytochrome P450 (CYP) enzymes, enhanced the antiandrogenic effect, indicating that the antiandrogenic effect is caused by intact species of DEPE constituents. The antiandrogenic effect of DEPE samples was reversed by alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist. The antiandrogenic activity of a DEPE sample correlated with its AhR agonist activity assayed in PC3/AR cells transiently transfected with CYP1A1 gene promoter-driven luciferase expression vector pLUC1A1. Equimolar mixtures of ten polycyclic aromatic hydrocarbons (PAHs) having four or more rings, structures found in the DEPEs, showed significant antiandrogenic effects and AhR agonist activity at concentrations equivalent to those found in DEPE samples. Further, DEPE samples elicited only antiandrogenic effects in recombinant yeast cells, which express beta-galactosidase in response to androgen. A competitive AR binding assay showed that AR-binding constituents exist in DEPE samples, indicating that greater part of AR-binding constituents in DEPEs are AR antagonists. All these findings show that DEPE samples exhibit significant antiandrogenic effect in cell-based transcription assay and that this effect is due in part to the constituents with AhR agonist activity including PAHs and to the constituents with AR antagonist activity.

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.

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...

Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis.

PubMed

Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun

2014-08-14

The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

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

Comparative transcriptional analysis provides new insights into the molecular basis of adventitious rooting recalcitrance in Eucalyptus.

PubMed

de Almeida, Márcia Rodrigues; de Bastiani, Daniela; Gaeta, Marcos Letaif; de Araújo Mariath, Jorge Ernesto; de Costa, Fernanda; Retallick, Jeffrey; Nolan, Lana; Tai, Helen H; Strömvik, Martina V; Fett-Neto, Arthur Germano

2015-10-01

Adventitious rooting (AR) is essential in clonal propagation. Eucalyptus globulus is relevant for the cellulose industry due to its low lignin content. However, several useful clones are recalcitrant to AR, often requiring exogenous auxin, adding cost to clonal garden operations. In contrast, E. grandis is an easy-to-root species widely used in clonal forestry. Aiming at contributing to the elucidation of recalcitrance causes in E. globulus, we conducted a comparative analysis with these two species differing in rooting competence, combining gene expression and anatomical techniques. Recalcitrance in E. globulus is reversed by exposure to exogenous indole-3-acetic acid (IAA), which promotes important gene expression modifications in both species. The endogenous content of IAA was significantly higher in E. grandis than in E. globulus. The cambium zone was identified as an active area during AR, concentrating the first cell divisions. Immunolocalization assay showed auxin accumulation in cambium cells, further indicating the importance of this region for rooting. We then performed a cambium zone-specific gene expression analysis during AR using laser microdissection. The results indicated that the auxin-related genes TOPLESS and IAA12/BODENLOS and the cytokinin-related gene ARR1may act as negative regulators of AR, possibly contributing to the hard-to-root phenotype of E. globulus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of Mental Workload in Online Shopping: Are Augmented and Virtual Reality Consistent?

PubMed

Zhao, Xiaojun; Shi, Changxiu; You, Xuqun; Zong, Chenming

2017-01-01

A market research company (Nielsen) reported that consumers in the Asia-Pacific region have become the most active group in online shopping. Focusing on augmented reality (AR), which is one of three major techniques used to change the method of shopping in the future, this study used a mixed design to discuss the influences of the method of online shopping, user gender, cognitive style, product value, and sensory channel on mental workload in virtual reality (VR) and AR situations. The results showed that males' mental workloads were significantly higher than females'. For males, high-value products' mental workload was significantly higher than that of low-value products. In the VR situation, the visual mental workload of field-independent and field-dependent consumers showed a significant difference, but the difference was reduced under audio-visual conditions. In the AR situation, the visual mental workload of field-independent and field-dependent consumers showed a significant difference, but the difference increased under audio-visual conditions. This study provided a psychological study of online shopping with AR and VR technology with applications in the future. Based on the perspective of embodied cognition, AR online shopping may be potential focus of research and market application. For the future design of online shopping platforms and the updating of user experience, this study provides a reference.

Analysis of Mental Workload in Online Shopping: Are Augmented and Virtual Reality Consistent?

PubMed Central

Zhao, Xiaojun; Shi, Changxiu; You, Xuqun; Zong, Chenming

2017-01-01

A market research company (Nielsen) reported that consumers in the Asia-Pacific region have become the most active group in online shopping. Focusing on augmented reality (AR), which is one of three major techniques used to change the method of shopping in the future, this study used a mixed design to discuss the influences of the method of online shopping, user gender, cognitive style, product value, and sensory channel on mental workload in virtual reality (VR) and AR situations. The results showed that males’ mental workloads were significantly higher than females’. For males, high-value products’ mental workload was significantly higher than that of low-value products. In the VR situation, the visual mental workload of field-independent and field-dependent consumers showed a significant difference, but the difference was reduced under audio–visual conditions. In the AR situation, the visual mental workload of field-independent and field-dependent consumers showed a significant difference, but the difference increased under audio–visual conditions. This study provided a psychological study of online shopping with AR and VR technology with applications in the future. Based on the perspective of embodied cognition, AR online shopping may be potential focus of research and market application. For the future design of online shopping platforms and the updating of user experience, this study provides a reference. PMID:28184207

Respiratory diseases and the impact of cough in Taiwan

PubMed Central

Lin, Horng-Chyuan; Cho, Sang-Heon; Ghoshal, Aloke Gopal; Muttalif, Abdul Razak Bin Abdul; Thanaviratananich, Sanguansak; Bagga, Shalini; Faruqi, Rab; Sajjan, Shiva; Cahill, Camilla L; Hamrosi, Kim K; Wang, De Yun

2016-01-01

Abstract Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of Respiratory Diseases (APBORD) study was a cross-sectional, observational study which examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across Asia-Pacific using 1 standard protocol. Here we report symptoms, healthcare resource use (HCRU), work impairment, and associated cost in Taiwan. Consecutive participants aged ≥ 18 years presenting to a physician with symptoms meeting the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Participants and their treating physician completed surveys detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Costs including direct medical costs and indirect costs associated with lost work productivity were calculated. The study enrolled 1001 patients. AR was the most frequent primary diagnosis (31.2%). A quarter of patients presented with a combination of respiratory diseases, with AR and asthma being the most frequent combination (14.1%). Cough or coughing up phlegm was the primary reason for the medical visit for patients with asthma and COPD, whereas nasal symptoms (watery runny nose, blocked nose, and congestion) were the primary reasons for AR and rhinosinusitis. Specialists were the most frequently used healthcare resource by patients with AR (26.1%), asthma (26.4%), COPD (26.6%), and rhinosinusitis (47.3%). The mean annual cost per patient with a respiratory disease was US$4511 (SD 5395). The cost was almost double for employed patients (US$8047, SD 6175), with the majority attributable to lost productivity. Respiratory diseases have a significant impact on disease burden in Taiwan. Treatment strategies that prevent lost work productivity could greatly reduce the economic burden of these diseases. PMID:27399064

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy.

PubMed

Liu, Vincent Wing Sun; Yau, Wing Lung; Tam, Chun Wai; Yao, Kwok-Ming; Shiu, Stephen Yuen Wing

2017-05-31

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin ( IL ) -6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy

PubMed Central

Liu, Vincent Wing Sun; Yau, Wing Lung; Tam, Chun Wai; Yao, Kwok-Ming; Shiu, Stephen Yuen Wing

2017-01-01

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT1 receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion. PMID:28561752

Direct Regulation of Androgen Receptor Activity by Potent CYP17 Inhibitors in Prostate Cancer Cells*

PubMed Central

Soifer, Harris S.; Souleimanian, Naira; Wu, Sijian; Voskresenskiy, Anatoliy M.; Kisaayak Collak, Filiz; Cinar, Bekir; Stein, Cy A.

2012-01-01

TOK-001 and abiraterone are potent 17-heteroarylsteroid (17-HAS) inhibitors of Cyp17, one of the rate-limiting enzymes in the biosynthesis of testosterone from cholesterol in prostate cancer cells. Nevertheless, the molecular mechanism underlying the prevention of prostate cell growth by 17-HASs still remains elusive. Here, we assess the effects of 17-HASs on androgen receptor (AR) activity in LNCaP and LAPC-4 cells. We demonstrate that both TOK-001 and abiraterone reduced AR protein and mRNA expression, and antagonized AR-dependent promoter activation induced by androgen. TOK-001, but not abiraterone, is an effective apparent competitor of the radioligand [3H]R1881 for binding to the wild type and various mutant AR (W741C, W741L) proteins. In agreement with these data, TOK-001 is a consistently superior inhibitor than abiraterone of R1881-induced transcriptional activity of both wild type and mutant AR. However, neither agent was able to trans-activate the AR in the absence of R1881. Our data demonstrate that phospho-4EBP1 levels are significantly reduced by TOK-001 and to a lesser extent by abiraterone alcohol, and suggest a mechanism by which cap-dependent translation is suppressed by blocking assembly of the eIF4F and eIF4G complex to the mRNA 5′ cap. Thus, the effects of these 17-HASs on AR signaling are complex, ranging from a decrease in testosterone production through the inhibition of Cyp17 as previously described, to directly reducing both AR protein expression and R1881-induced AR trans-activation. PMID:22174412

A novel class of pyranocoumarin anti-androgen receptor signaling compounds.

PubMed

Guo, Junming; Jiang, Cheng; Wang, Zhe; Lee, Hyo-Jeong; Hu, Hongbo; Malewicz, Barbara; Lee, Hyo-Jung; Lee, Jae-Ho; Baek, Nam-In; Jeong, Jin-Hyun; Kim, Dae-Keun; Kang, Kyung-Sun; Kim, Sung-Hoon; Lu, Junxuan

2007-03-01

Androgen and the androgen receptor (AR)-mediated signaling are crucial for prostate cancer development. Novel agents that can inhibit AR signaling in ligand-dependent and ligand-independent manners are desirable for the chemoprevention of prostate carcinogenesis and for the treatment of advanced prostate cancer. We have shown recently that the pyranocoumarin compound decursin from the herb Angelica gigas possesses potent anti-AR activities distinct from the anti-androgen bicalutamide. Here, we compared the anti-AR activities and the cell cycle arrest and apoptotic effects of decursin and two natural analogues in the androgen-dependent LNCaP human prostate cancer cell culture model to identify structure-activity relationships and mechanisms. Decursin and its isomer decursinol angelate decreased prostate-specific antigen expression with IC(50) of approximately 1 mumol/L. Both inhibited the androgen-stimulated AR nuclear translocation and transactivation, decreased AR protein abundance through proteasomal degradation, and induced G(0/1) arrest and morphologic differentiation. They also induced caspase-mediated apoptosis and reactive oxygen species at higher concentrations. Furthermore, they lacked the agonist activity of bicalutamide in the absence of androgen and were more potent than bicalutamide for suppressing androgen-stimulated cell growth. Decursinol, which does not contain a side chain, lacked the reactive oxygen species induction and apoptotic activities and exerted paradoxically an inhibitory and a stimulatory effect on AR signaling and cell growth. In conclusion, decursin and decursinol angelate are members of a novel class of nonsteroidal compounds that exert a long-lasting inhibition of both ligand-dependent and ligand-independent AR signaling. The side chain is critical for sustaining the anti-AR activities and the growth arrest and apoptotic effects.

7 CFR 504.5 - Address.

Code of Federal Regulations, 2010 CFR

2010-01-01

... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815 N...

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.

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.

CHROMOSPHERIC MASS MOTIONS AND INTRINSIC SUNSPOT ROTATIONS FOR NOAA ACTIVE REGIONS 10484, 10486, AND 10488 USING ISOON DATA

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

Hardersen, Paul S.; Balasubramaniam, K. S.; Shkolyar, Svetlana, E-mail: Hardersen@space.edu

2013-08-10

This work utilizes Improved Solar Observing Optical Network continuum (630.2 nm) and H{alpha} (656.2 nm) data to: (1) detect and measure intrinsic sunspot rotations occurring in the photosphere and chromosphere, (2) identify and measure chromospheric filament mass motions, and (3) assess any large-scale photospheric and chromospheric mass couplings. Significant results from 2003 October 27-29, using the techniques of Brown et al., indicate significant counter-rotation between the two large sunspots in NOAA AR 10486 on October 29, as well as discrete filament mass motions in NOAA AR 10484 on October 27 that appear to be associated with at least one C-classmore » solar flare.« less

Efficacy of Lysine-Specific Demethylase 1 Inhibition in PCa

DTIC Science & Technology

2016-08-01

specific demethylase 1 (LSD1) forms a complex with CoREST and has been well-characterized as an epigenetic regulator that mediates transcriptional...castration-resistant prostate cancer (CRPC), where AR activity persists and its function may be altered by epigenetic mechanisms. Specifically, we...hypothesized that LSD1 activity in PCa may allow tumor cells to epigenetically reprogram the AR cistrome by closing AR binding sites through which AR

Larvicidal and Biting Deterrent Activity of Essential Oils of Curcuma longa, Ar-turmerone, and Curcuminoids Against Aedes aegypti and Anopheles quadrimaculatus (Culicidae: Diptera).

PubMed

Ali, Abbas; Wang, Yan-Hong; Khan, Ikhlas A

2015-09-01

Essential oils and extract of Curcuma longa, ar-turmerone, and curcuminoids were evaluated for their larvicidal and deterrent activity against mosquitoes. Ar-turmerone and curcuminoids constituted 36.9, 24.9 and 50.6% of rhizome oil, leaf oil, and rhizome extract, respectively. Ar-turmerone was the major compound of the rhizome oil (36.9%) and leaf oil (24.9%). The ethanolic extract had 15.4% ar-turmerone with 6.6% bisdesmethoxycurcumin, 6.1% desmethoxycurcumin, and 22.6% curcumin. In in vitro studies, essential oils of the leaf (biting deterrence index [BDI] = 0.98), rhizome (BDI = 0.98), and rhizome ethanolic extract (BDI = 0.96) at 10 µg/cm(2) showed biting deterrent activity similar to DEET at 25 nmol/cm(2) against Aedes aegypti L. Among the pure compounds, ar-turmerone (BDI = 1.15) showed the biting deterrent activity higher than DEET at 25 nmol/cm(2) whereas the activity of other compounds was lower than DEET. In Anopheles quadrimaculatus Say, only ar-turmerone showed deterrent activity similar to DEET. In dose-response bioassay, ar-turmerone showed significantly higher biting deterrence than DEET at all the dosages. Ar-turmerone, at 15 nmol/cm(2), showed activity similar to DEET at 25 nmol/cm(2) and activity at 5 nmol/cm(2) was similar to DEET at 20 and 15 nmol/cm(2). Leaf essential oil with LC(50) values of 1.8 and 8.9 ppm against larvae of An. quadrimaculatus and Ae. aegypti, respectively, showed highest toxicity followed by rhizome oil and ethanolic extract. Among the pure compounds, ar-turmerone with LC(50) values of 2.8 and 2.5 ppm against larvae of An. quadrimaculatus and Ae. aegypti, respectively, was most toxic followed by bisdesmethoxycurcumin, curcumin, and desmethoxycurcumin. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

N deposition affects allelopathic potential of Amaranthus retroflexus with different distribution regions.

PubMed

Wang, Congyan; Liu, Jun; Zhou, Jiawei

2017-01-01

This study aims to determine the allelopathic potential of Amaranthus retroflexus (Ar) with different climatic zones on seed germination and growth of A. tricolor (At) treated with a gradient N addition. Ar leaf extracts only displayed significantly allelopathic potential on the underground growth of Ar but not the aboveground growth of At. The allelopathic potential of Ar leaf extracts on root length of At were enhanced under N addition and there may be a N-concentration-dependent relationship. The effects of the extracts of Ar leaves that collected from Zhenjiang on seed germination and growth of At may be higher than that collected from Jinan especially on root length of At under medium N addition. This reason may be the contained higher concentration of secondary metabolites for the leaves of plants that growths in high latitudes compare with that growth in low latitudes. This phenomenon may also partly be attributed to the fact that Ar originated in America and/or south-eastern Asia which have higher similarity climate conditions as Zhenjiang rather than Jinan. The allelopathic potential of Ar on seed germination and growth of acceptor species may play an important role in its successful invasion especially in the distribution region with low latitudes.

Atmospheric river influence on the intensification of extreme hydrologic events over the Western United States under climate change scenarios

NASA Astrophysics Data System (ADS)

Pagán, Brianna; Ashfaq, Moetasim; Nayak, Munir; Rastogi, Deeksha; Margulis, Steven; Pal, Jeremy

2017-04-01

The Western United States shares limited snowmelt driven water supplies amongst millions of people, a multi-billion dollar agriculture industry and fragile ecosystems. The climatology of the region is highly variable, characterized by the frequent occurrences of both flood and drought conditions that cause increasingly challenging water management issues. Although variable year to year, up to half of California's total precipitation can be linked to atmospheric rivers (ARs). Most notably, ARs have been connected to nearly every major historic flood in the region, establishing its critical role to water supply. Numerous prior studies have considered potential climate change impacts over the Western United States and have generally concluded that warmer temperatures will reduce snowpack and shift runoff timing, causing reductions to water supply. Here we examine the role of ARs as one mechanism for explaining projected increases in flood and drought frequency and intensity under climate change scenarios, vital information for water resource managers. A hierarchical modeling framework to downscale 11 coupled global climate models from CMIP5 is used to form an ensemble of high-resolution dynamically downscaled regional climate model (via RegCM4) simulations at 18-km and hydrological (via VIC) simulations at a 4-km resolution for baseline (1965-2005) and future (2010-2050) periods under RCP 8.5. Each ensemble member's ability to capture observational AR climatology over the baseline period is evaluated. Baseline to future period changes to AR size, duration, seasonal timing, trajectory, magnitude and frequency are presented. These changes to the characterizations of ARs in the region are used to determine if any links exist to changes in snowpack volume, runoff timing, and the occurrence of daily and annual cumulative extreme precipitation and runoff events. Shifts in extreme AR frequency and magnitude are expected to increase flood risks, which without adequate multi-year reservoir storage solutions could further strain water supply resources.