Evolution of seafloor spreading rate based on Ar-40 degassing history

NASA Astrophysics Data System (ADS)

Tajika, Eiichi; Matsui, Takafumi

1993-05-01

A new degassing model of Ar-40 coupled with thermal evolution of the mantle is constructed to constrain the temporal variation of seafloor spreading rate. In this model, we take into account the effects of elemental partition and solubility during melt generation and bubble formation, and changes in both seafloor spreading rate and melt generation depth in the mantle. It is suggested that the seafloor spreading rate would have been almost the same as that of today over the history of the earth in order to explain the present amount of Ar-40 in the atmosphere. This result may also imply the mild degassing history of volatiles from the mantle.

Three-dimensional dominant frequency mapping using autoregressive spectral analysis of atrial electrograms of patients in persistent atrial fibrillation.

PubMed

Salinet, João L; Masca, Nicholas; Stafford, Peter J; Ng, G André; Schlindwein, Fernando S

2016-03-08

Areas with high frequency activity within the atrium are thought to be 'drivers' of the rhythm in patients with atrial fibrillation (AF) and ablation of these areas seems to be an effective therapy in eliminating DF gradient and restoring sinus rhythm. Clinical groups have applied the traditional FFT-based approach to generate the three-dimensional dominant frequency (3D DF) maps during electrophysiology (EP) procedures but literature is restricted on using alternative spectral estimation techniques that can have a better frequency resolution that FFT-based spectral estimation. Autoregressive (AR) model-based spectral estimation techniques, with emphasis on selection of appropriate sampling rate and AR model order, were implemented to generate high-density 3D DF maps of atrial electrograms (AEGs) in persistent atrial fibrillation (persAF). For each patient, 2048 simultaneous AEGs were recorded for 20.478 s-long segments in the left atrium (LA) and exported for analysis, together with their anatomical locations. After the DFs were identified using AR-based spectral estimation, they were colour coded to produce sequential 3D DF maps. These maps were systematically compared with maps found using the Fourier-based approach. 3D DF maps can be obtained using AR-based spectral estimation after AEGs downsampling (DS) and the resulting maps are very similar to those obtained using FFT-based spectral estimation (mean 90.23 %). There were no significant differences between AR techniques (p = 0.62). The processing time for AR-based approach was considerably shorter (from 5.44 to 5.05 s) when lower sampling frequencies and model order values were used. Higher levels of DS presented higher rates of DF agreement (sampling frequency of 37.5 Hz). We have demonstrated the feasibility of using AR spectral estimation methods for producing 3D DF maps and characterised their differences to the maps produced using the FFT technique, offering an alternative approach for 3D DF computation in human persAF studies.

Evaluation of Parameter Uncertainty Reduction in Groundwater Flow Modeling Using Multiple Environmental Tracers

NASA Astrophysics Data System (ADS)

Arnold, B. W.; Gardner, P.

2013-12-01

Calibration of groundwater flow models for the purpose of evaluating flow and aquifer heterogeneity typically uses observations of hydraulic head in wells and appropriate boundary conditions. Environmental tracers have a wide variety of decay rates and input signals in recharge, resulting in a potentially broad source of additional information to constrain flow rates and heterogeneity. A numerical study was conducted to evaluate the reduction in uncertainty during model calibration using observations of various environmental tracers and combinations of tracers. A synthetic data set was constructed by simulating steady groundwater flow and transient tracer transport in a high-resolution, 2-D aquifer with heterogeneous permeability and porosity using the PFLOTRAN software code. Data on pressure and tracer concentration were extracted at well locations and then used as observations for automated calibration of a flow and transport model using the pilot point method and the PEST code. Optimization runs were performed to estimate parameter values of permeability at 30 pilot points in the model domain for cases using 42 observations of: 1) pressure, 2) pressure and CFC11 concentrations, 3) pressure and Ar-39 concentrations, and 4) pressure, CFC11, Ar-39, tritium, and He-3 concentrations. Results show significantly lower uncertainty, as indicated by the 95% linear confidence intervals, in permeability values at the pilot points for cases including observations of environmental tracer concentrations. The average linear uncertainty range for permeability at the pilot points using pressure observations alone is 4.6 orders of magnitude, using pressure and CFC11 concentrations is 1.6 orders of magnitude, using pressure and Ar-39 concentrations is 0.9 order of magnitude, and using pressure, CFC11, Ar-39, tritium, and He-3 concentrations is 1.0 order of magnitude. Data on Ar-39 concentrations result in the greatest parameter uncertainty reduction because its half-life of 269 years is similar to the range of transport times (hundreds to thousands of years) in the heterogeneous synthetic aquifer domain. The slightly higher uncertainty range for the case using all of the environmental tracers simultaneously is probably due to structural errors in the model introduced by the pilot point regularization scheme. It is concluded that maximum information and uncertainty reduction for constraining a groundwater flow model is obtained using an environmental tracer whose half-life is well matched to the range of transport times through the groundwater flow system. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Consistent force field modeling of matrix isolated molecules. V. Minimum energy path potential to the conformer conversion of 1,2-difluoroethane: Ar 364, ab initio calculation of electric multipole moments and electric polarization contribution to the conversion barrier

NASA Astrophysics Data System (ADS)

Gunde, R.; Ha, T.-K.; Günthard, H. H.

1990-08-01

In this paper results of consistent force field modeling (CFF) of the potential function to conversion of the gauche (g) to the trans (t) conformer of 1,2-difluoroethane (DFE) isolated in an argon matrix will be reported. Starting point are locally stable configurations gDFE:Ar 364 (defect GH1) and tDFE:Ar 364 (TH1) obtained in previous work from CFF modeling of a cube shaped Ar 364 fragment containing one DFE molecule in its center. Using the dihedral angle of DFE as an independent parameter the minimum energy path of the conversion process gDFE:Ar 364→tDFE:Ar 364 will be determined by CFF energy minimization. Determination of the minimum energy path is found to require large numbers of energy minimization steps and to lead to a rather complicated motion of the molecule with respect to the crystal fragment. Surprisingly the molecule-matrix interactions lead to a reduction of the g-t barrier by ≈500 cal/mol and to a stabilization of the trans species by ≈500 cal/mol. This finding is a consequence of a delicate interplay of matrix-molecule and matrix-matrix interactions. Calculation of the electric polarization energy (induced dipole-first-order polarization approximation) is based on extended ab initio calculations of dipole and quadrupole moments and a bond polarizability estimate of the first-order polarizability of DFE as a function of the internal rotation angle, on Fourier expansion of multipole components and use of symmetry for reduction of the order of the linear system defining the (self-consistent) induced dipole moments of all Ar atoms. Electric polarization is found to alter the potential function of the conversion process in a profound way: the g-t barrier and the t-g energy difference are increased to ≈3000 cal/mol and to ≈1500 cal/mol respectively (≈2500 and ≈530 cal/mol respectively for free DFE). Further applications of the technique developed in this work to related problems of matrix isolated molecules, e.g., vibrational matrix shifts will be discussed.

The ChArMEx database

NASA Astrophysics Data System (ADS)

Ferré, Hélène; Belmahfoud, Nizar; Boichard, Jean-Luc; Brissebrat, Guillaume; Cloché, Sophie; Descloitres, Jacques; Fleury, Laurence; Focsa, Loredana; Henriot, Nicolas; Mière, Arnaud; Ramage, Karim; Vermeulen, Anne; Boulanger, Damien

2015-04-01

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr/) aims 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 project includes long term monitoring of environmental parameters , intensive field campaigns, use of satellite data and modelling studies. Therefore ChARMEx scientists produce and need to access a wide diversity of data. In this context, the objective of the database task is to organize data management, distribution system and services, such as facilitating the exchange of information and stimulating the collaboration between researchers within the ChArMEx community, and beyond. The database relies on a strong collaboration between ICARE, IPSL and OMP data centers and has been set up in the framework of the Mediterranean Integrated Studies at Regional And Locals Scales (MISTRALS) program data portal. ChArMEx data, either produced or used by the project, are documented and accessible through the database website: http://mistrals.sedoo.fr/ChArMEx. The website offers the usual but user-friendly functionalities: data catalog, user registration procedure, search tool to select and access data... The metadata (data description) are standardized, and comply with international standards (ISO 19115-19139; INSPIRE European Directive; Global Change Master Directory Thesaurus). A Digital Object Identifier (DOI) assignement procedure allows to automatically register the datasets, in order to make them easier to access, cite, reuse and verify. At present, the ChArMEx database contains about 120 datasets, including more than 80 in situ datasets (2012, 2013 and 2014 summer campaigns, background monitoring station of Ersa...), 25 model output sets (dust model intercomparison, MEDCORDEX scenarios...), a high resolution emission inventory over the Mediterranean... Many in situ datasets have been inserted in a relational database, in order to enable more accurate selection and download of different datasets in a shared format. Many dedicated satellite products (SEVIRI, TRIMM, PARASOL...) are processed and will soon be accessible through the database website. In order to meet the operational needs of the airborne and ground based observational teams during the ChArMEx campaigns, a day-to-day chart display website has been developed and operated: http://choc.sedoo.org. It offers a convenient way to browse weather conditions and chemical composition during the campaign periods. Every scientist is invited to visit the ChArMEx websites, to register and to request data. Feel free to contact charmex-database@sedoo.fr for any question.

[The effect of 18β-sodium glycyrrhetinic acid on the nasal mucosa epithelial cilia in rat models of allergic rhinitis].

PubMed

Yang, Jing; Xi, Kehu; Gui, Yan; Wang, Youhu; Zhang, Fuhong; Ma, Chunxia; Hong, Hao; Liu, Xiangyi; Meng, Nannan; Zhang, Xiaobing

2015-12-01

To investigate 18β-sodium glycyrrhetinic acid impact on nasal mucosa epithelial cilia in rat models of allergic rhinitis (AR). AR models were established by ovalbumin-induction. Wister rats were randomly divided into groups as normal group, model group, budesonide (0.2 mg/kg) group and sodium glycyrrhetinic acid (20 mg/kg and 40 mg/kg) group after the success of AR models. At 2 weeks and 4 weeks after treatment, the behavioral changes of rats were observed and recorded, and nasal septum mucosae were collected after 2 week and 4 week intervention, and the morphological changes of nasal mucosae were observed by electron microscope. Model group developed typical AR symptoms, the total score in all animals was > 5. With budesonide and sodium glycyrrhetinic acid treatment, the AR symptoms were relieved, and the total scores were reduced significantly (P < 0.01). Compared with the model group: after 2 weeks' intervention, thick mucous secretions on the top of columnar epithelium cilia in rat nasal mucosa was significantly reduced, and cilia adhesion, lodging, shedding were relieved in budesonide group and sodium glycyrrhetinic acid group, the relieve in budesonide group was slightly better than that in sodium glycyrrhetinic acid group; after 4 week intervention, Cilia adhesion, lodging, shedding were completely vanished, and the cilia were ranged in regular direction in budesonide group and sodium glycyrrhetinic acid group. Cilia in sodium glycyrrhetinic acid (20 mg/kg) group was more orderly, smooth than that in budesonide group and sodium glycyrrhetinic acid group (40 mg/kg), and the condition of cilia in sodium glycyrrhetinic acid group (20 mg/kg) was similar to the normal group. 18β-sodium glycyrrhetinic acid is effective to restrain the pathological changes of nasal mucosa cilia in rat models of AR.

Towards cybernetic surgery: robotic and augmented reality-assisted liver segmentectomy.

PubMed

Pessaux, Patrick; Diana, Michele; Soler, Luc; Piardi, Tullio; Mutter, Didier; Marescaux, Jacques

2015-04-01

Augmented reality (AR) in surgery consists in the fusion of synthetic computer-generated images (3D virtual model) obtained from medical imaging preoperative workup and real-time patient images in order to visualize unapparent anatomical details. The 3D model could be used for a preoperative planning of the procedure. The potential of AR navigation as a tool to improve safety of the surgical dissection is outlined for robotic hepatectomy. Three patients underwent a fully robotic and AR-assisted hepatic segmentectomy. The 3D virtual anatomical model was obtained using a thoracoabdominal CT scan with a customary software (VR-RENDER®, IRCAD). The model was then processed using a VR-RENDER® plug-in application, the Virtual Surgical Planning (VSP®, IRCAD), to delineate surgical resection planes including the elective ligature of vascular structures. Deformations associated with pneumoperitoneum were also simulated. The virtual model was superimposed to the operative field. A computer scientist manually registered virtual and real images using a video mixer (MX 70; Panasonic, Secaucus, NJ) in real time. Two totally robotic AR segmentectomy V and one segmentectomy VI were performed. AR allowed for the precise and safe recognition of all major vascular structures during the procedure. Total time required to obtain AR was 8 min (range 6-10 min). Each registration (alignment of the vascular anatomy) required a few seconds. Hepatic pedicle clamping was never performed. At the end of the procedure, the remnant liver was correctly vascularized. Resection margins were negative in all cases. The postoperative period was uneventful without perioperative transfusion. AR is a valuable navigation tool which may enhance the ability to achieve safe surgical resection during robotic hepatectomy.

Prediction of Muscle Performance During Dynamic Repetitive Exercise

NASA Technical Reports Server (NTRS)

Byerly, D. L.; Byerly, K. A.; Sognier, M. A.; Squires, W. G.

2002-01-01

A method for predicting human muscle performance was developed. Eight test subjects performed a repetitive dynamic exercise to failure using a Lordex spinal machine. Electromyography (EMG) data was collected from the erector spinae. Evaluation of the EMG data using a 5th order Autoregressive (AR) model and statistical regression analysis revealed that an AR parameter, the mean average magnitude of AR poles, can predict performance to failure as early as the second repetition of the exercise. Potential applications to the space program include evaluating on-orbit countermeasure effectiveness, maximizing post-flight recovery, and future real-time monitoring capability during Extravehicular Activity.

An accurate nonlinear stochastic model for MEMS-based inertial sensor error with wavelet networks

NASA Astrophysics Data System (ADS)

El-Diasty, Mohammed; El-Rabbany, Ahmed; Pagiatakis, Spiros

2007-12-01

The integration of Global Positioning System (GPS) with Inertial Navigation System (INS) has been widely used in many applications for positioning and orientation purposes. Traditionally, random walk (RW), Gauss-Markov (GM), and autoregressive (AR) processes have been used to develop the stochastic model in classical Kalman filters. The main disadvantage of classical Kalman filter is the potentially unstable linearization of the nonlinear dynamic system. Consequently, a nonlinear stochastic model is not optimal in derivative-based filters due to the expected linearization error. With a derivativeless-based filter such as the unscented Kalman filter or the divided difference filter, the filtering process of a complicated highly nonlinear dynamic system is possible without linearization error. This paper develops a novel nonlinear stochastic model for inertial sensor error using a wavelet network (WN). A wavelet network is a highly nonlinear model, which has recently been introduced as a powerful tool for modelling and prediction. Static and kinematic data sets are collected using a MEMS-based IMU (DQI-100) to develop the stochastic model in the static mode and then implement it in the kinematic mode. The derivativeless-based filtering method using GM, AR, and the proposed WN-based processes are used to validate the new model. It is shown that the first-order WN-based nonlinear stochastic model gives superior positioning results to the first-order GM and AR models with an overall improvement of 30% when 30 and 60 seconds GPS outages are introduced.

QAARM: quasi-anharmonic autoregressive model reveals molecular recognition pathways in ubiquitin

PubMed Central

Savol, Andrej J.; Burger, Virginia M.; Agarwal, Pratul K.; Ramanathan, Arvind; Chennubhotla, Chakra S.

2011-01-01

Motivation: Molecular dynamics (MD) simulations have dramatically improved the atomistic understanding of protein motions, energetics and function. These growing datasets have necessitated a corresponding emphasis on trajectory analysis methods for characterizing simulation data, particularly since functional protein motions and transitions are often rare and/or intricate events. Observing that such events give rise to long-tailed spatial distributions, we recently developed a higher-order statistics based dimensionality reduction method, called quasi-anharmonic analysis (QAA), for identifying biophysically-relevant reaction coordinates and substates within MD simulations. Further characterization of conformation space should consider the temporal dynamics specific to each identified substate. Results: Our model uses hierarchical clustering to learn energetically coherent substates and dynamic modes of motion from a 0.5 μs ubiqutin simulation. Autoregressive (AR) modeling within and between states enables a compact and generative description of the conformational landscape as it relates to functional transitions between binding poses. Lacking a predictive component, QAA is extended here within a general AR model appreciative of the trajectory's temporal dependencies and the specific, local dynamics accessible to a protein within identified energy wells. These metastable states and their transition rates are extracted within a QAA-derived subspace using hierarchical Markov clustering to provide parameter sets for the second-order AR model. We show the learned model can be extrapolated to synthesize trajectories of arbitrary length. Contact: ramanathana@ornl.gov; chakracs@pitt.edu PMID:21685101

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.

Laboratory calibration of density-dependent lines in the extreme ultraviolet spectral region

NASA Astrophysics Data System (ADS)

Lepson, J. K.; Beiersdorfer, P.; Gu, M. F.; Desai, P.; Bitter, M.; Roquemore, L.; Reinke, M. L.

2012-05-01

We have been making spectral measurements in the extreme ultraviolet (EUV) from different laboratory sources in order to investigate the electron density dependence of various astrophysically important emission lines and to test the atomic models underlying the diagnostic line ratios. The measurement are being performed at the Livermore EBIT-I electron beam ion trap, the National Spherical Torus Experiment (NSTX) at Princeton, and the Alcator C-Mod tokamak at the Massachusetts Institute of Technology, which together span an electron density of four orders of magnitude and which allow us to test the various models at high and low density limits. Here we present measurements of Fe XXII and Ar XIV, which include new data from an ultra high resolution (λ/Δλ >4000) spectrometer at the EBIT-I facility. We found good agreement between the measurements and modeling calculations for Fe XXII, but poorer agreement for Ar XIV.

Augmented reality system

NASA Astrophysics Data System (ADS)

Lin, Chien-Liang; Su, Yu-Zheng; Hung, Min-Wei; Huang, Kuo-Cheng

2010-08-01

In recent years, Augmented Reality (AR)[1][2][3] is very popular in universities and research organizations. The AR technology has been widely used in Virtual Reality (VR) fields, such as sophisticated weapons, flight vehicle development, data model visualization, virtual training, entertainment and arts. AR has characteristics to enhance the display output as a real environment with specific user interactive functions or specific object recognitions. It can be use in medical treatment, anatomy training, precision instrument casting, warplane guidance, engineering and distance robot control. AR has a lot of vantages than VR. This system developed combines sensors, software and imaging algorithms to make users feel real, actual and existing. Imaging algorithms include gray level method, image binarization method, and white balance method in order to make accurate image recognition and overcome the effects of light.

76 FR 20783 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... rates and descriptive information about Auction Rate Securities (``ARS'') and Variable Rate Demand... interest rate setting mechanisms for ARS and liquidity facilities for VDROs, information about orders submitted for an ARS auction, and additional information about VRDOs.\\5\\ To provide subscribers with access...

Evolution of short range order in Ar: Liquid to glass and solid transitions-A computational study

NASA Astrophysics Data System (ADS)

Shor, Stanislav; Yahel, Eyal; Makov, Guy

2018-04-01

The evolution of the short range order (SRO) as a function of temperature in a Lennard-Jones model liquid with Ar parameters was determined and juxtaposed with thermodynamic and kinetic properties obtained as the liquid was cooled (heated) and transformed between crystalline solid or glassy states and an undercooled liquid. The Lennard-Jones system was studied by non-equilibrium molecular dynamics simulations of large supercells (approximately 20000 atoms) rapidly cooled or heated at selected quenching rates and at constant pressure. The liquid to solid transition was identified by discontinuities in the atomic volume and molar enthalpy; the glass transition temperature range was identified from the temperature dependence of the self-diffusion. The SRO was studied within the quasi-crystalline model (QCM) framework and compared with the Steinhardt bond order parameters. Within the QCM it was found that the SRO evolves from a bcc-like order in the liquid through a bct-like short range order (c/a=1.2) in the supercooled liquid which persists into the glass and finally to a fcc-like ordering in the crystalline solid. The variation of the SRO that results from the QCM compares well with that obtained with Steinhardt's bond order parameters. The hypothesis of icosahedral order in liquids and glasses is not supported by our results.

A reevaluation of the proposed spin-down of the white dwarf pulsar in AR Scorpii.

NASA Astrophysics Data System (ADS)

Potter, Stephen B.; Buckley, David A. H.

2018-05-01

We present high-speed optical photometric observations, spanning ˜2 years, of the recently-discovered white dwarf pulsar AR Scorpii. The amplitudes of the orbital, spin and beat modulations appear to be remarkably stable and repeatable over the time span of our observations. It has been suggested that the polarized and non-polarized emission from AR Scorpii is powered by the spin-down of the white dwarf. However, we find that our new data is inconsistent with the published spin-down ephemeris. Whilst our data is consistent with a constant spin period further observations over an extended time-base are required in order to ascertain the true spin-evolution of the white dwarf. This may have implications for the various models put forward to explain the energetics and evolution of AR Scorpii.

Electron-impact ionization of Ne (2 p ) and Ar (3 p ) at intermediate energies: Role of the postcollision interaction

NASA Astrophysics Data System (ADS)

Hu, Xiaoqing; Gao, Cong-Zhang; Chen, Zhanbin; Wang, Jianguo; Wu, Yong; Wang, Yang

2017-11-01

We present the absolute triple differential cross section (TDCS) for single ionization of Ne (2 p ) at an impact energy of 599.6 eV and Ar (3 p ) at 195 eV. The role of the postcollision interaction (PCI) is studied using a high-order distorted-wave Born approximation model with a continuum distorted-waves expansion. Both the second- and third-order effects are considered in the present calculations, and the third-order distorted wave Born approximation model is reported in the (e ,2 e ) reaction. The calculated results show satisfactory agreement with experimental data. The magnitude of the absolute TDCS is enhanced by a factor 2-3 when the strength factor γ of the PCI amplitude is summarized just from 0 to 2. This proves that the PCI plays an important role in the absolute TDCS of the (e ,2 e ) reaction in the intermediate-energy region.

Ab initio based study of the ArO- photoelectron spectra: Selectivity of spin-orbit transitions

NASA Astrophysics Data System (ADS)

Buchachenko, A. A.; Jakowski, Jacek; Chałasiński, Grzegorz; Szczȩśniak, M. M.; Cybulski, S. M.

2000-04-01

A combined ab initio atoms-in-molecule approach was implemented to model the photoelectron spectra of the ArO- anion. The lowest adiabatic states of Σ and Π symmetry of ArO and ArO- were investigated using the fourth-order Møller-Plessett perturbation theory including bond functions. The total energies were dissected into electrostatic, exchange, induction, and dispersion components. The complex of Ar with atomic oxygen is only weakly bound, primarily by dispersion interaction. The Π state possesses a deeper minimum (Re=3.4Å,De=380μEh) than the Σ state (Re=3.8Å,De=220μEh). In contrast, the anion complex is fairly strongly bound, primarily by ion-induced dipole induction forces, and the Σ state possesses a deeper minimum at shorter interatomic distances (Re=3.02Å,De=3600μEh) than the Π state (Re=3.35Å,De=2400μEh). The Σ-Π splittings in both systems are mainly due to differences in the exchange repulsion terms. Atoms-in-molecule models were used to account for the spin-orbit interaction, and to generate adiabatic relativistic potentials and wave functions. Collisional properties, diffusion, and mobility coefficients of O and O- in Ar, and absolute total Ar+O scattering cross sections, were calculated and found to agree well with the available experimental data. The photoelectron spectra were simulated within vibronic model, and were found in excellent agreement with the experimental measurements. The bimodal electron kinetic energy distribution was shown to stem from the strong selectivity of spin-orbit transitions, which split into two dense groups, depending on the initial electronic state of the anion. The latter feature cannot be described without explicit consideration of electronic intensity factor.

South Polar Ar Enhancement as a Tracer for Southern Winter Horizontal Meridional Mixing

NASA Technical Reports Server (NTRS)

Sprague, A. L.; Boynton, W. V.; Kim, K.; Reedy, R.; Kerry, K.; Janes, D.

2004-01-01

Measurements made by the Gamma Ray Spectrometer (GRS) on Mars Odyssey during 2002 and 2003 show an obvious increase in the gamma flux of 1294 keV gamma rays resulting from the decay of (41)Ar. (41)Ar is made by the capture of thermal neutrons by atmospheric (40)Ar. The increase measured above the southern polar region has permitted calculation of the increase in mixing ratio of Ar from L(sub s) 8 to 100 between latitudes 75 S and 90 S. The peak in Ar enhancement occurs about 200 Earth days after CO2 freeze-out has begun, indicating that up to this time equatorward meridional mixing is rapid enough to move enhanced Ar from the polar regions northward. Although the CO2 frost depth continues to increase from L(sub s) 110 deg to 190 deg, the Ar enhancement steadily decreases to its baseline value reached at about L(sub s) 200 deg. Our data permit an estimate of the horizontal eddy mixing coefficient useful for constraining equatorward meridional mixing during southern winter and a characteristic mixing time for the polar southern winter atmosphere. Also, using the drop in excess Ar measured by the GRS from L(sub s) 110 deg to 200 deg, we estimate an eddy coefficient appropriate for meridional mixing of the entire Ar excess back to the baseline value. The horizontal eddy mixing coefficients are derived using Ar as a tracer much as the vertical eddy mixing coefficient for the Earth's troposphere is derived using CH4 as a minor constituent tracer. The estimation of meridional mixing for high latitudes at Mars is important for constraining parameters used in atmospheric modeling and predicting seasonal and daily behavior. The calculations are order of magnitude estimates that should improve as the data set becomes more robust and improves our models.

Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling.

PubMed

Tilli, Tatiana Martins; Ferreira, Luciana Bueno; Gimba, Etel Rodrigues Pereira

2015-04-01

Androgen receptor (AR) signaling is a key pathway modulating prostate cancer (PCa) progression. Several steps in this pathway have been investigated in order to propose novel treatment strategies for advanced PCa. Total osteopontin (OPN) has been described as a biomarker for PCa, in addition to its role in activating the progression of this tumor. Based on the known effects of the OPNc splice variant on PCa progression, the present study investigated whether this isoform can also modulate AR signaling. In order to test this, an in vitro model was used in which LNCaP cells were cultured in the presence of conditioned medium (CM) secreted by PCa cells overexpressing OPNc (OPNc-CM). The activation of AR signaling was evaluated by measuring the expression levels of AR-responsive genes (ARGs) using quantitative polymerase chain reaction and specific oligonucleotides. The data demonstrated that all nine tested ARGs ( Fgf8 , TMPRSS2 , Greb1 , Cdk2 , Ndrg1 , Cdk1 , Pmepa1 , Psa and Ar ) are significantly upregulated in response to OPNc-CM compared with LNCaP cells cultured in CM secreted by control cells transfected with empty expression vector. The specific involvement of OPNc was demonstrated by depleting OPNc from OPNc-CM using an anti-OPNc neutralizing antibody. In addition, by using a phosphoinositide 3-kinase (PI3K)-specific inhibitor and AR antagonists, such as flutamide and bicalutamide, it was also observed that upregulation of ARGs in response to OPNc-CM involves PI3K signaling and depends on the AR. In conclusion, these data indicated that OPNc is able to activate AR signaling through the PI3K pathway and the AR. These data further corroborate our previous data, revealing the OPNc splice variant to be a key molecule that is able to modulate key signaling pathways involved in PCa progression.

Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling

PubMed Central

TILLI, TATIANA MARTINS; FERREIRA, LUCIANA BUENO; GIMBA, ETEL RODRIGUES PEREIRA

2015-01-01

Androgen receptor (AR) signaling is a key pathway modulating prostate cancer (PCa) progression. Several steps in this pathway have been investigated in order to propose novel treatment strategies for advanced PCa. Total osteopontin (OPN) has been described as a biomarker for PCa, in addition to its role in activating the progression of this tumor. Based on the known effects of the OPNc splice variant on PCa progression, the present study investigated whether this isoform can also modulate AR signaling. In order to test this, an in vitro model was used in which LNCaP cells were cultured in the presence of conditioned medium (CM) secreted by PCa cells overexpressing OPNc (OPNc-CM). The activation of AR signaling was evaluated by measuring the expression levels of AR-responsive genes (ARGs) using quantitative polymerase chain reaction and specific oligonucleotides. The data demonstrated that all nine tested ARGs (Fgf8, TMPRSS2, Greb1, Cdk2, Ndrg1, Cdk1, Pmepa1, Psa and Ar) are significantly upregulated in response to OPNc-CM compared with LNCaP cells cultured in CM secreted by control cells transfected with empty expression vector. The specific involvement of OPNc was demonstrated by depleting OPNc from OPNc-CM using an anti-OPNc neutralizing antibody. In addition, by using a phosphoinositide 3-kinase (PI3K)-specific inhibitor and AR antagonists, such as flutamide and bicalutamide, it was also observed that upregulation of ARGs in response to OPNc-CM involves PI3K signaling and depends on the AR. In conclusion, these data indicated that OPNc is able to activate AR signaling through the PI3K pathway and the AR. These data further corroborate our previous data, revealing the OPNc splice variant to be a key molecule that is able to modulate key signaling pathways involved in PCa progression. PMID:25789054

Potential predictability and forecast skill in ensemble climate forecast: the skill-persistence rule

NASA Astrophysics Data System (ADS)

Jin, Y.; Rong, X.; Liu, Z.

2017-12-01

This study investigates the factors that impact the forecast skill for the real world (actual skill) and perfect model (perfect skill) in ensemble climate model forecast with a series of fully coupled general circulation model forecast experiments. It is found that the actual skill of sea surface temperature (SST) in seasonal forecast is substantially higher than the perfect skill on a large part of the tropical oceans, especially the tropical Indian Ocean and the central-eastern Pacific Ocean. The higher actual skill is found to be related to the higher observational SST persistence, suggesting a skill-persistence rule: a higher SST persistence in the real world than in the model could overwhelm the model bias to produce a higher forecast skill for the real world than for the perfect model. The relation between forecast skill and persistence is further examined using a first-order autoregressive model (AR1) analytically for theoretical solutions and numerically for analogue experiments. The AR1 model study shows that the skill-persistence rule is strictly valid in the case of infinite ensemble size, but can be distorted by the sampling error and non-AR1 processes.

A quantitative analysis of attitudes and behaviours concerning sustainable parasite control practices from Scottish sheep farmers.

PubMed

Jack, Corin; Hotchkiss, Emily; Sargison, Neil D; Toma, Luiza; Milne, Catherine; Bartley, David J

2017-04-01

Nematode control in sheep, by strategic use of anthelmintics, is threatened by the emergence of roundworms populations that are resistant to one or more of the currently available drugs. In response to growing concerns of Anthelmintic Resistance (AR) development in UK sheep flocks, the Sustainable Control of Parasites in Sheep (SCOPS) initiative was set up in 2003 in order to promote practical guidelines for producers and advisors. To facilitate the uptake of 'best practice' approaches to nematode management, a comprehensive understanding of the various factors influencing sheep farmers' adoption of the SCOPS principles is required. A telephone survey of 400 Scottish sheep farmers was conducted to elicit attitudes regarding roundworm control, AR and 'best practice' recommendations. A quantitative statistical analysis approach using structural equation modelling was chosen to test the relationships between both observed and latent variables relating to general roundworm control beliefs. A model framework was developed to test the influence of socio-psychological factors on the uptake of sustainable (SCOPS) and known unsustainable (AR selective) roundworm control practices. The analysis identified eleven factors with significant influences on the adoption of SCOPS recommended practices and AR selective practices. Two models established a good fit with the observed data with each model explaining 54% and 47% of the variance in SCOPS and AR selective behaviours, respectively. The key influences toward the adoption of best practice parasite management, as well as demonstrating negative influences on employing AR selective practices were farmer's base line understanding about roundworm control and confirmation about lack of anthelmintic efficacy in a flock. The findings suggest that improving farmers' acceptance and uptake of diagnostic testing and improving underlying knowledge and awareness about nematode control may influence adoption of best practice behaviour. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting.

PubMed

Eloma, Amanda S; Tucciarone, Jason M; Hayes, Edmund M; Bronson, Brian D

2018-01-01

The Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) is an assessment tool used to quantify alcohol withdrawal syndrome (AWS) severity and inform benzodiazepine treatment for alcohol withdrawal. To evaluate the prescribing patterns and appropriate use of the CIWA-Ar protocol in a general hospital setting, as determined by the presence or absence of documented AWS risk factors, patients' ability to communicate, and provider awareness of the CIWA-Ar order. This retrospective chart review included 118 encounters of hospitalized patients placed on a CIWA-Ar protocol during one year. The following data were collected for each encounter: patient demographics, admitting diagnosis, ability to communicate, and admission blood alcohol level; and medical specialty of the clinician ordering CIWA-Ar, documentation of the presence or absence of established AWS risk factors, specific parameters of the protocol ordered, service admitted to, provider documentation of awareness of the active protocol within 48 h of initial order, total benzodiazepine dose equivalents administered and associated adverse events. 57% of patients who started on a CIWA-Ar protocol had either zero or one documented risk factor for AWS (19% and 38% respectively). 20% had no documentation of recent alcohol use. 14% were unable to communicate. 19% of medical records lacked documentation of provider awareness of the ordered protocol. Benzodiazepine associated adverse events were documented in 15% of encounters. The judicious use of CIWA-Ar protocols in general hospitals requires mechanisms to ensure assessment of validated alcohol withdrawal risk factors, exclusion of patients who cannot communicate, and continuity of care during transitions.

Response surface methodological approach for the decolorization of simulated dye effluent using Aspergillus fumigatus fresenius.

PubMed

Sharma, Praveen; Singh, Lakhvinder; Dilbaghi, Neeraj

2009-01-30

The aim of our research was to study, effect of temperature, pH and initial dye concentration on decolorization of diazo dye Acid Red 151 (AR 151) from simulated dye solution using a fungal isolate Aspergillus fumigatus fresenius have been investigated. The central composite design matrix and response surface methodology (RSM) have been applied to design the experiments to evaluate the interactive effects of three most important operating variables: temperature (25-35 degrees C), pH (4.0-7.0), and initial dye concentration (100-200 mg/L) on the biodegradation of AR 151. The total 20 experiments were conducted in the present study towards the construction of a quadratic model. Very high regression coefficient between the variables and the response (R(2)=0.9934) indicated excellent evaluation of experimental data by second-order polynomial regression model. The RSM indicated that initial dye concentration of 150 mg/L, pH 5.5 and a temperature of 30 degrees C were optimal for maximum % decolorization of AR 151 in simulated dye solution, and 84.8% decolorization of AR 151 was observed at optimum growth conditions.

Computing and Applying Atomic Regulons to Understand Gene Expression and Regulation

PubMed Central

Faria, José P.; Davis, James J.; Edirisinghe, Janaka N.; Taylor, Ronald C.; Weisenhorn, Pamela; Olson, Robert D.; Stevens, Rick L.; Rocha, Miguel; Rocha, Isabel; Best, Aaron A.; DeJongh, Matthew; Tintle, Nathan L.; Parrello, Bruce; Overbeek, Ross; Henry, Christopher S.

2016-01-01

Understanding gene function and regulation is essential for the interpretation, prediction, and ultimate design of cell responses to changes in the environment. An important step toward meeting the challenge of understanding gene function and regulation is the identification of sets of genes that are always co-expressed. These gene sets, Atomic Regulons (ARs), represent fundamental units of function within a cell and could be used to associate genes of unknown function with cellular processes and to enable rational genetic engineering of cellular systems. Here, we describe an approach for inferring ARs that leverages large-scale expression data sets, gene context, and functional relationships among genes. We computed ARs for Escherichia coli based on 907 gene expression experiments and compared our results with gene clusters produced by two prevalent data-driven methods: Hierarchical clustering and k-means clustering. We compared ARs and purely data-driven gene clusters to the curated set of regulatory interactions for E. coli found in RegulonDB, showing that ARs are more consistent with gold standard regulons than are data-driven gene clusters. We further examined the consistency of ARs and data-driven gene clusters in the context of gene interactions predicted by Context Likelihood of Relatedness (CLR) analysis, finding that the ARs show better agreement with CLR predicted interactions. We determined the impact of increasing amounts of expression data on AR construction and find that while more data improve ARs, it is not necessary to use the full set of gene expression experiments available for E. coli to produce high quality ARs. In order to explore the conservation of co-regulated gene sets across different organisms, we computed ARs for Shewanella oneidensis, Pseudomonas aeruginosa, Thermus thermophilus, and Staphylococcus aureus, each of which represents increasing degrees of phylogenetic distance from E. coli. Comparison of the organism-specific ARs showed that the consistency of AR gene membership correlates with phylogenetic distance, but there is clear variability in the regulatory networks of closely related organisms. As large scale expression data sets become increasingly common for model and non-model organisms, comparative analyses of atomic regulons will provide valuable insights into fundamental regulatory modules used across the bacterial domain. PMID:27933038

Can we model observed soil carbon changes from a dense inventory? A case study over England and Wales using three versions of the ORCHIDEE ecosystem model (AR5, AR5-PRIM and O-CN)

NASA Astrophysics Data System (ADS)

Guenet, B.; Moyano, F. E.; Vuichard, N.; Kirk, G. J. D.; Bellamy, P. H.; Zaehle, S.; Ciais, P.

2013-12-01

A widespread decrease of the topsoil carbon content was observed over England and Wales during the period 1978-2003 in the National Soil Inventory (NSI), amounting to a carbon loss of 4.44 Tg yr-1 over 141 550 km2. Subsequent modelling studies have shown that changes in temperature and precipitation could only account for a small part of the observed decrease, and therefore that changes in land use and management and resulting changes in heterotrophic respiration or net primary productivity were the main causes. So far, all the models used to reproduce the NSI data have not accounted for plant-soil interactions and have only been soil carbon models with carbon inputs forced by data. Here, we use three different versions of a process-based coupled soil-vegetation model called ORCHIDEE (Organizing Carbon and Hydrology in Dynamic Ecosystems), in order to separate the effect of trends in soil carbon input from soil carbon mineralization induced by climate trends over 1978-2003. The first version of the model (ORCHIDEE-AR5), used for IPCC-AR5 CMIP5 Earth System simulations, is based on three soil carbon pools defined with first-order decomposition kinetics, as in the CENTURY model. The second version (ORCHIDEE-AR5-PRIM) built for this study includes a relationship between litter carbon and decomposition rates, to reproduce a priming effect on decomposition. The last version (O-CN) takes into account N-related processes. Soil carbon decomposition in O-CN is based on CENTURY, but adds N limitations on litter decomposition. We performed regional gridded simulations with these three versions of the ORCHIDEE model over England and Wales. None of the three model versions was able to reproduce the observed NSI soil carbon trend. This suggests either that climate change is not the main driver for observed soil carbon losses or that the ORCHIDEE model even with priming or N effects on decomposition lacks the basic mechanisms to explain soil carbon change in response to climate, which would raise a caution flag about the ability of this type of model to project soil carbon changes in response to future warming. A third possible explanation could be that the NSI measurements made on the topsoil are not representative of the total soil carbon losses integrated over the entire soil depth, and thus cannot be compared with the model output.

Can we model observed soil carbon changes from a dense inventory? A case study over england and wales using three version of orchidee ecosystem model (AR5, AR5-PRIM and O-CN)

NASA Astrophysics Data System (ADS)

Guenet, B.; Moyano, F. E.; Vuichard, N.; Kirk, G. J. D.; Bellamy, P. H.; Zaehle, S.; Ciais, P.

2013-07-01

A widespread decrease of the top soil carbon content was observed over England and Wales during the period 1978-2003 in the National Soil Inventory (NSI), amounting to a carbon loss of 4.44 Tg yr-1 over 141 550 km2. Subsequent modelling studies have shown that changes in temperature and precipitation could only account for a small part of the observed decrease, and therefore that changes in land use and management and resulting changes in soil respiration or primary production were the main causes. So far, all the models used to reproduce the NSI data did not account for plant-soil interactions and were only soil carbon models with carbon inputs forced by data. Here, we use three different versions of a process-based coupled soil-vegetation model called ORCHIDEE, in order to separate the effect of trends in soil carbon input, and soil carbon mineralisation induced by climate trends over 1978-2003. The first version of the model (ORCHIDEE-AR5) used for IPCC-AR5 CMIP5 Earth System simulations, is based on three soil carbon pools defined with first order decomposition kinetics, as in the CENTURY model. The second version (ORCHIDEE-AR5-PRIM) built for this study includes a relationship between litter carbon and decomposition rates, to reproduce a priming effect on decomposition. The last version (O-CN) takes into account N-related processes. Soil carbon decomposition in O-CN is based on CENTURY, but adds N limitations on litter decomposition. We performed regional gridded simulations with these three versions of the ORCHIDEE model over England and Wales. None of the three model versions was able to reproduce the observed NSI soil carbon trend. This suggests that either climate change is not the main driver for observed soil carbon losses, or that the ORCHIDEE model even with priming or N-effects on decomposition lacks the basic mechanisms to explain soil carbon change in response to climate, which would raise a caution flag about the ability of this type of model to project soil carbon changes in response to future warming. A third possible explanation could be that the NSI measurements made on the topsoil are not representative of the total soil carbon losses integrated over the entire soil depth, and thus cannot be compared with the model output.

The ChArMEx database

NASA Astrophysics Data System (ADS)

Ferré, Helene; Belmahfoud, Nizar; Boichard, Jean-Luc; Brissebrat, Guillaume; Descloitres, Jacques; Fleury, Laurence; Focsa, Loredana; Henriot, Nicolas; Mastrorillo, Laurence; Mière, Arnaud; Vermeulen, Anne

2014-05-01

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr/) aims 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 project includes long term monitoring of environmental parameters, intensive field campaigns, use of satellite data and modelling studies. Therefore ChARMEx scientists produce and need to access a wide diversity of data. In this context, the objective of the database task is to organize data management, distribution system and services, such as facilitating the exchange of information and stimulating the collaboration between researchers within the ChArMEx community, and beyond. The database relies on a strong collaboration between OMP and ICARE data centres and has been set up in the framework of the Mediterranean Integrated Studies at Regional And Locals Scales (MISTRALS) program data portal. All the data produced by or of interest for the ChArMEx community will be documented in the data catalogue and accessible through the database website: http://mistrals.sedoo.fr/ChArMEx. At present, the ChArMEx database contains about 75 datasets, including 50 in situ datasets (2012 and 2013 campaigns, Ersa background monitoring station), 25 model outputs (dust model intercomparison, MEDCORDEX scenarios), and a high resolution emission inventory over the Mediterranean. Many in situ datasets have been inserted in a relational database, in order to enable more accurate data selection and download of different datasets in a shared format. The database website offers different tools: - A registration procedure which enables any scientist to accept the data policy and apply for a user database account. - A data catalogue that complies with metadata international standards (ISO 19115-19139; INSPIRE European Directive; Global Change Master Directory Thesaurus). - Metadata forms to document observations or products that will be provided to the database. - A search tool to browse the catalogue using thematic, geographic and/or temporal criteria. - A shopping-cart web interface to order in situ data files. - A web interface to select and access to homogenized datasets. Interoperability between the two data centres is being set up using the OPEnDAP protocol. The data portal will soon propose a user-friendly access to satellite products managed by the ICARE data centre (SEVIRI, TRIMM, PARASOL...). In order to meet the operational needs of the airborne and ground based observational teams during the ChArMEx 2012 and 2013 campaigns, a day-to-day chart and report display website has been developed too: http://choc.sedoo.org. It offers a convenient way to browse weather conditions and chemical composition during the campaign periods.

Atmospheric rivers causing high accumulation storms in East Antarctica: regional climate model evaluation

NASA Astrophysics Data System (ADS)

Lazzara, M. A.; Tsukernik, M.; Gorodetskaya, I.

2016-12-01

Recent studies confirmed that atmospheric rivers (ARs) reach the continent of Antarctica and thus influence the Antarctic accumulation patterns and the ice sheet mass balance (Gorodetskaya et al. 2014, GRL). Similar to mid-latitude ARs, Antarctic ARs are associated with a blocking pattern downstream of a cyclone, which allows channeling of moisture toward the continent. However, due to the extremely cold atmosphere, Antarctic ARs possess some unique features. First, the existence of an AR in high latitudes is always associated with warm advection. Second, in order for an AR to penetrate the continent, it needs to overcome strong low-level outflow winds - katabatic winds - coming from the interior of the continent. Thirdly, sea ice surrounding the Antarctic ice sheet introduces an additional "cold barrier" decreasing the tropospheric moisture holding capacity and promoting precipitation before reaching the ice sheet. We believe these factors contribute to the scarcity of AR events influencing the ice sheet surface mass balance. Nevertheless, their presence is clearly seen in the long-term record. In particular, anomalous accumulation in 2009 and 2011 in Dronning Maud Land in East Antarctica has been linked to atmospheric rivers. We performed a detailed investigation of several AR storm events from 2009 and 2011 using the Weather Research and Forecasting (WRF) model simulations. These simulations depicted the synoptic scale development of storms that led to an anomalous precipitation pattern in the East Antarctic. We investigated the role of the upper level vs. lower level forcing in the formation of the contributing storms. The moisture and temperature anomalies of each case are evaluated in the context of synoptic and large-scale atmospheric forcing. We also performed sensitivity studies to determine the role of sea ice in the development of these systems.

A Tale of Two Earths: Reconciling the Lunar and Terrestrial Hadean Records

NASA Astrophysics Data System (ADS)

Boehnke, Patrick

Studying early Earth history is complicated by the fact that the rock record doesn't extend past 4 Ga and our only record for the Hadean (>4 Ga) comes to us from detrital zircons from the Jack Hills in Western Australia. The Hadean zircon record extends back to almost 4.4 Ga and has revealed that the early Earth may have had liquid water, a felsic crust, plate boundary interactions, and possibly a biosphere. On the other hand, analyses of lunar and meteoritic samples are used to argue for a hellish Hadean Earth where frequent, large impactors repeatedly destroyed the crust. Indeed, these two models stand in direct contradiction. The focus of this thesis is to examine the evidence for these two models and ultimately propose a reconciliation based on a new interpretation of the chronology of the lunar samples used to constrain the impact history into the early Earth-Moon system. In order to improve the understanding of zircon crystallization in igneous settings, we undertook experimental studies of zircon saturation which were analyzed using a novel ion imaging approach by a secondary ion mass spectrometer. This study confirmed the original model for zircon saturation, that it is a function of only temperature, melt composition, and Zr content. Indeed, the primary implication for the early Earth from this work is that zircons are much more likely to crystallize in a felsic rather than mafic magma and therefore simply the existence of Hadean zircons suggests a high likelihood for felsic Hadean magmatism. The majority of the thesis focuses on the interpretation of 40 Ar/39Ar ages of lunar and meteorite samples, specifically with regards to impact histories derived from compilations of such ages. The primary complication with lunar and meteorite 40Ar/ 39Ar ages is that the vast majority show evidence for later disturbances due to diffusive loss of 40Ar. To try and extract meaningful thermal histories from these samples, we undertook investigations of samples from Apollo 16 and the Jilin chondrite. We then used an extension of the multi-domain diffusion model that can model samples containing multiple activation energies (i.e., whole rock samples with multiple K bearing minerals) to propose that the 40Ar/39Ar system can be used to recover shock heating temperatures and durations. Having shown the effects of diffusive 40Ar loss on the accuracy of 40Ar/39Ar dating, we then explored the question as to whether or not compilations of disturbed 40Ar/ 39Ar ages simply misestimate the timing of bombardment episodes or are fundamentally inaccurate. For this we created a simple numerical model that simulates a chosen impact history on a surface and then creates a histogram of 40Ar/39Ar plateau ages. Our results show that rather than simply misestimate timing, compilations of 40Ar/ 39Ar ages can lead to inferences of illusory bombardment episodes. Finally, we examine the 40Ar/39Ar ages of suite of geochemically related Apollo 16 rocks to examine the effects of mixing and brecciation on the accuracy of inferred ages. By analyzing multiple rocks from each soil sample, we show that three out of six samples are not compatible with a single thermal history. That is to say, despite their close proximity during sampling and geochemical similarities, analyzed rocks in the soil sample have unique chronologies. Based on these findings, we developed a simple numerical model which shows that internal isochrons of mixed samples can yield erroneous ages while retaining a statistically acceptable mean squared weighted deviation (MSWD).

XRD-based 40Ar/39Ar age correction for fine-grained illite, with application to folded carbonates in the Monterrey Salient (northern Mexico)

NASA Astrophysics Data System (ADS)

Fitz-Díaz, Elisa; Hall, Chris M.; van der Pluijm, Ben A.

2016-05-01

Due to their minute size, 40Ar/39Ar analysis of illite faces significant analytical challenges, including mineral characterization and, especially, effects of grain size and crystallography on 39Ar recoil. Quantifying the effects of 39Ar recoil requires the use of sample vacuum encapsulation during irradiation, which permits the measurement of the fraction of recoiled 39Ar as well as the 39Ar and 40Ar∗ retained within illite crystals that are released during step heating. Total-Gas Ages (TGA) are calculated by using both recoiled and retained argon, which is functionally equivalent to K-Ar ages, while Retention Ages (RA) only involve retained Ar in the crystal. Natural applications have shown that TGA fits stratigraphic constraints of geological processes when the average illite crystallite thickness (ICT) is smaller than 10 nm, and that RA matches these constraints for ICTs larger than 50 nm. We propose a new age correction method that takes into account the average ICT and corresponding recoiled 39Ar for a sample, with X-ray Corrected Ages (XCA) lying between Total-Gas and Retention Ages depending on ICT. This correction is particularly useful in samples containing authigenic illite formed in the anchizone, with typical ICT values between 10 and 50 nm. In three samples containing authigenic illite from Cretaceous carbonates in the Monterrey Salient in northern Mexico, there is a range in TGAs among the different size-fractions of 46-49, 36-43 and 40-52 Ma, while RAs range from 54-64, 47-52 and 53-54 Ma, respectively. XCA calculations produce tighter age ranges for these samples of 52.5-56, 45.5-48.5 and 49-52.5 Ma, respectively. In an apparent age vs ICT or %2M 1illite plot, authigenic illite grains show a slope that is in general slightly positive for TGA, slightly negative for RA, but close to zero for XCA, with thinner crystallites showing more dispersion than thicker ones. In order to test if dispersion is due to a different formation history or the result of retention capability, degassing spectra were modeled for site XCA averages and overall XCA average. Modeling shows that local site age average best match the measured spectra, instead of a global average age, indicating that illite growth reflects local deformation, and is not the result of regional metamorphism. Modeling also shows that Ar-degassing spectra are very sensitive to grain size, such that age interpretation based on Ar-plateaus is meaningless for most fine-grained clays.

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

Making Sense of Teacher Participants' Graphic Organizers in a Second Order Action Research: Reflection of the Voice of an Action Researcher

ERIC Educational Resources Information Center

Hwa, Chuah Kim

2012-01-01

Being a facilitator of AR (action research) to a group of secondary school teachers in Kuching, Sarawak provided me the opportunity to engage in a second order inquiry using AR on the two years' AR learning workshops concerned. The teacher participants were asked to illustrate, using suitable GOs (graphic organizers), their understanding of what…

archAR: an archaeological augmented reality experience

NASA Astrophysics Data System (ADS)

Wiley, Bridgette; Schulze, Jürgen P.

2015-03-01

We present an application for Android phones or tablets called "archAR" that uses augmented reality as an alternative, portable way of viewing archaeological information from UCSD's Levantine Archaeology Laboratory. archAR provides a unique experience of flying through an archaeological dig site in the Levantine area and exploring the artifacts uncovered there. Using a Google Nexus tablet and Qualcomm's Vuforia API, we use an image target as a map and overlay a three-dimensional model of the dig site onto it, augmenting reality such that we are able to interact with the plotted artifacts. The user can physically move the Android device around the image target and see the dig site model from any perspective. The user can also move the device closer to the model in order to "zoom" into the view of a particular section of the model and its associated artifacts. This is especially useful, as the dig site model and the collection of artifacts are very detailed. The artifacts are plotted as points, colored by type. The user can touch the virtual points to trigger a popup information window that contains details of the artifact, such as photographs, material descriptions, and more.

Vibrational and rotational energy transfers involving the CH B 2Σ- v=1 vibrational level in collisions with Ar, CO, and N2O

NASA Astrophysics Data System (ADS)

Huang, Hong-Yi; Tsai, Ming-Tsang; Lin, King-Chuen

2006-04-01

With photolysis-probe technique, we have studied vibrational and rotational energy transfers of CH involving the B Σ-2 (v =1, 0⩽N⩽6, F) state by collisions with Ar, CO, and N2O. For the vibrational energy transfer (VET) measurements, the time-resolved fluorescence of the B-X(0,0) band is monitored following the (1,0) band excitation. For the rotational energy transfer (RET) measurements, the laser-induced fluorescence of the initially populated state is dispersed using a step-scan Fourier transform spectrometer. The time-resolved spectra obtained in the nanosecond regime may yield the RET information under a single pressure of the collider. The rate constants of intramolecular energy transfers are evaluated with simulation of kinetic models. The VET lies in the range of 4×10-12to4×10-11cm3molecule-1s-1, with efficiency following the order of Ar

High-expression β(1) adrenergic receptor/cell membrane chromatography method based on a target receptor to screen active ingredients from traditional Chinese medicines.

PubMed

Yue, Yuan; Xue, Hui; Wang, Xin; Yang, Qian; Song, Yanhong; Li, Xiaoni

2014-02-01

β-Adrenergic receptors are important targets for drug discovery. We have developed a new β1 -adrenergic receptor cell membrane chromatography (β1 AR-CMC) with offline ultra-performance LC (UPLC) and MS method for screening active ingredients from traditional Chinese medicines. In this study, Chinese hamster ovary-S cells with high β1 AR expression levels were established and used to prepare a cell membrane stationary phase in a β1 AR-CMC model. The retention fractions were separated and identified by the UPLC-MS system. The screening results found that isoimperatorin from Rhizoma et Radix Notopterygii was the targeted component that could act on β1 AR in similar manner of metoprolol as a control drug. In addition, the biological effects of active component were also investigated in order to search for a new type of β1 AR antagonist. It will be a useful method for drug discovery as a leading compound resource. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Predicting long-term catchment nutrient export: the use of nonlinear time series models

NASA Astrophysics Data System (ADS)

Valent, Peter; Howden, Nicholas J. K.; Szolgay, Jan; Komornikova, Magda

2010-05-01

After the Second World War the nitrate concentrations in European water bodies changed significantly as the result of increased nitrogen fertilizer use and changes in land use. However, in the last decades, as a consequence of the implementation of nitrate-reducing measures in Europe, the nitrate concentrations in water bodies slowly decrease. This causes that the mean and variance of the observed time series also changes with time (nonstationarity and heteroscedascity). In order to detect changes and properly describe the behaviour of such time series by time series analysis, linear models (such as autoregressive (AR), moving average (MA) and autoregressive moving average models (ARMA)), are no more suitable. Time series with sudden changes in statistical characteristics can cause various problems in the calibration of traditional water quality models and thus give biased predictions. Proper statistical analysis of these non-stationary and heteroscedastic time series with the aim of detecting and subsequently explaining the variations in their statistical characteristics requires the use of nonlinear time series models. This information can be then used to improve the model building and calibration of conceptual water quality model or to select right calibration periods in order to produce reliable predictions. The objective of this contribution is to analyze two long time series of nitrate concentrations of the rivers Ouse and Stour with advanced nonlinear statistical modelling techniques and compare their performance with traditional linear models of the ARMA class in order to identify changes in the time series characteristics. The time series were analysed with nonlinear models with multiple regimes represented by self-exciting threshold autoregressive (SETAR) and Markov-switching models (MSW). The analysis showed that, based on the value of residual sum of squares (RSS) in both datasets, SETAR and MSW models described the time-series better than models of the ARMA class. In most cases the relative improvement of SETAR models against AR models of first order was low ranging between 1% and 4% with the exception of the three-regime model for the River Stour time-series where the improvement was 48.9%. In comparison, the relative improvement of MSW models was between 44.6% and 52.5 for two-regime and from 60.4% to 75% for three-regime models. However, the visual assessment of models plotted against original datasets showed that despite a high value of RSS, some ARMA models could describe the analyzed time-series better than AR, MA and SETAR models with lower values of RSS. In both datasets MSW models provided a very good visual fit describing most of the extreme values.

[Primary branch size of Pinus koraiensis plantation: a prediction based on linear mixed effect model].

PubMed

Dong, Ling-Bo; Liu, Zhao-Gang; Li, Feng-Ri; Jiang, Li-Chun

2013-09-01

By using the branch analysis data of 955 standard branches from 60 sampled trees in 12 sampling plots of Pinus koraiensis plantation in Mengjiagang Forest Farm in Heilongjiang Province of Northeast China, and based on the linear mixed-effect model theory and methods, the models for predicting branch variables, including primary branch diameter, length, and angle, were developed. Considering tree effect, the MIXED module of SAS software was used to fit the prediction models. The results indicated that the fitting precision of the models could be improved by choosing appropriate random-effect parameters and variance-covariance structure. Then, the correlation structures including complex symmetry structure (CS), first-order autoregressive structure [AR(1)], and first-order autoregressive and moving average structure [ARMA(1,1)] were added to the optimal branch size mixed-effect model. The AR(1) improved the fitting precision of branch diameter and length mixed-effect model significantly, but all the three structures didn't improve the precision of branch angle mixed-effect model. In order to describe the heteroscedasticity during building mixed-effect model, the CF1 and CF2 functions were added to the branch mixed-effect model. CF1 function improved the fitting effect of branch angle mixed model significantly, whereas CF2 function improved the fitting effect of branch diameter and length mixed model significantly. Model validation confirmed that the mixed-effect model could improve the precision of prediction, as compare to the traditional regression model for the branch size prediction of Pinus koraiensis plantation.

Modelling Atmospheric Rivers and the Potential for Southeast Texas Flooding: A Case Study of the Maya Express and the March 2016 Sabine River Flood

NASA Astrophysics Data System (ADS)

McIntosh, J.; Lander, K.

2016-12-01

For three days in March of 2016, southeast Texas was inundated with up to 19 inches of rainfall, swelling the Sabine River to record flood stages. This event was attributed to an atmospheric river (AR), regionally known as the "Maya Express," which carried moisture from the Gulf of Mexico into the Sabine River Basin. Studies by the NOAA/NWS Climate Prediction Center have shown that ARs are occurring more frequently due to the intensification of El Niño that increases the available moisture in the atmosphere. In this study, we analyzed the hydrological and meteorological setup of the event on the Sabine River to characterize the flood threat associated with AR rainfall and simulated how an equivalent AR event would impact an urban basin in Houston, Texas. Our primary data sources included WSR-88D radar-based rainfall estimates and observed data at USGS river gauges. Furthermore, the land surface parameters evaluated included land cover, soil types, basin topology, model-derived soil moisture states, and topography. The spatial distribution of precipitation from the storm was then translated west over the Houston and used to force a hydrologic model to assess the impact of an event comparable to the March 2016 event on Houston's San Jacinto River Basin. The results indicate that AR precipitation poses a flood risk to urbanized areas in southeast Texas because of the low lying topography, impervious pavement, and limited flood control. Due to this hydrologic setup, intense AR rainfall can yield a rapid urban runoff response that overwhelms the river system, potentially endangering the lives and property of millions of people in the Houston area. Ultimately, if the frequency of AR development increases, regional flood potential may increase. Given the consequences established in this study, more research should be conducted in order to better predict the rate of recurrence and effects of Maya Express generated precipitation.

Mycotoxin Management Studies by USDA-ARS, NCAUR in 2009

USDA-ARS?s Scientific Manuscript database

Studies again included several popcorn fields in 2009 in order to continue gathering data for modification of the previously developed management strategies for mycotoxins in field corn (including the mycotoxin predictive computer program). Without an attempt for optimization, the field corn model ...

Potential predictability and forecast skill in ensemble climate forecast: a skill-persistence rule

NASA Astrophysics Data System (ADS)

Jin, Yishuai; Rong, Xinyao; Liu, Zhengyu

2017-12-01

This study investigates the factors relationship between the forecast skills for the real world (actual skill) and perfect model (perfect skill) in ensemble climate model forecast with a series of fully coupled general circulation model forecast experiments. It is found that the actual skill for sea surface temperature (SST) in seasonal forecast is substantially higher than the perfect skill on a large part of the tropical oceans, especially the tropical Indian Ocean and the central-eastern Pacific Ocean. The higher actual skill is found to be related to the higher observational SST persistence, suggesting a skill-persistence rule: a higher SST persistence in the real world than in the model could overwhelm the model bias to produce a higher forecast skill for the real world than for the perfect model. The relation between forecast skill and persistence is further proved using a first-order autoregressive model (AR1) analytically for theoretical solutions and numerically for analogue experiments. The AR1 model study shows that the skill-persistence rule is strictly valid in the case of infinite ensemble size, but could be distorted by sampling errors and non-AR1 processes. This study suggests that the so called "perfect skill" is model dependent and cannot serve as an accurate estimate of the true upper limit of real world prediction skill, unless the model can capture at least the persistence property of the observation.

Population pharmacokinetics of ticagrelor and AR-C124910XX in patients with prior myocardial infarction
.

PubMed

Röshammar, Daniel; Bergstrand, Martin; Andersson, Tomas; Storey, Robert F; Hamrén, Bengt

2017-05-01

The population pharmacokinetics of ticagrelor and its active metabolite AR-C124910XX were characterized following ticagrelor 60 mg or 90 mg twice daily oral long-term treatment in 4,426 patients with a history of myocardial infarction. The ticagrelor and AR-C124910XX plasma concentration-time data were described by one-compartment models with first-order absorption or metabolite formation and elimination. Systemic exposure to ticagrelor and AR-C124910XX were stable over time. Ticagrelor apparent clearance (CL/F) was 17 L/h for the 60-mg and 15.4 L/h for the 90-mg dose. The CL/F of AR-C124910XX was 11.1 L/h for the 60-mg and 9.95 L/h for the 90-mg dose. Both ticagrelor and AR-C124910XX CL/F were independently influenced by body weight, sex, age, smoking, and Japanese ethnicity. Female sex and age > 75 years were the only categorical covariates, having more than 20% effect on AR-C124910XX CL/F. Ticagrelor CL/F was 6% higher and 11% lower, whereas AR-C124910XX CL/F was 26% higher and 34% lower for patients weighing 110 and 50 kg, respectively, compared with an 83 kg patient. The small differences in exposure to both ticagrelor and AR-C124910XX between demographic subgroups were in accordance with the consistent efficacy and safety outcomes observed across the population. The results were similar to those observed previously in patients with acute coronary syndromes.
.

Five millions years of paleosecular variations from the Golan Heights volcanic field, Israel

NASA Astrophysics Data System (ADS)

Behar, N.; Shaar, R.; Asefaw, H.; Ebert, Y.; Koppers, A.; Tauxe, L.

2017-12-01

One of the most fundamental assumption in paleomagnetism is that the averaged geomagnetic field on geological timescales is a geocentric axial dipole (GAD). Given the first order importance of the GAD hypothesis, it is essential to rigorously test its validity and to understand the limits of its use. Additionally, it is equally vital to characterize statistically paleomagnetic secular variations (PSV) over timescales of 106 years. The Plio-Pleistocene volcanic field in the Golan Heights, Israel (32.7°N-33.3°N) is a nearly ideal location to investigate these issues, owing to excellent exposure of basaltic flows, dated using more than 100 radiometric (K/Ar and Ar/Ar) ages covering the past 5 Myr. Here we present new data from 89 basalt flows from the Golan Heights with ages spanning from 5.4 Ma to 0.1 Ma, and 18 new Ar/Ar ages. This relatively large dataset allows us to calculate three different Virtual Geomagnetic Poles (VGP): Pleistocene, Pliocene, and a combined Plio-Pleistocene. From each pole we calculate the inclination anomaly (ΔI) and the VGP scatter parameter (SB). The Pleistocene pole yields a VGP scatter parameter around SB =13, lower than predictions of PSV models. Also, it demonstrates negligible inclination anomaly of less than 2°, suggesting validation of the GAD model. The Pliocene pole shows a larger scatter (SB 18) and a negative inclination anomaly around ΔI = -7°. We discuss these results in view of the worldwide paleomagnetic database and the available PSV models.

Static and Impulsive Models of Solar Active Regions

NASA Technical Reports Server (NTRS)

Patsourakos, S.; Klimchuk, James A.

2008-01-01

The physical modeling of active regions (ARs) and of the global coronal is receiving increasing interest lately. Recent attempts to model ARs using static equilibrium models were quite successful in reproducing AR images of hot soft X-ray (SXR) loops. They however failed to predict the bright EUV warm loops permeating ARs: the synthetic images were dominated by intense footpoint emission. We demonstrate that this failure is due to the very weak dependence of loop temperature on loop length which cannot simultaneously account for both hot and warm loops in the same AR. We then consider time-dependent AR models based on nanoflare heating. We demonstrate that such models can simultaneously reproduce EUV and SXR loops in ARs. Moreover, they predict radial intensity variations consistent with the localized core and extended emissions in SXR and EUV AR observations respectively. We finally show how the AR morphology can be used as a gauge of the properties (duration, energy, spatial dependence, repetition time) of the impulsive heating.

ORION Environmental Control and Life Support Systems Suit Loop and Pressure Control Analysis

NASA Technical Reports Server (NTRS)

Eckhardt, Brad; Conger, Bruce; Stambaugh, Imelda C.

2015-01-01

Under NASA's ORION Multi-Purpose Crew Vehicle (MPCV) Environmental Control and Life Support System (ECLSS) Project at Johnson Space Center's (JSC), the Crew and Thermal Systems Division has developed performance models of the air system using Thermal Desktop/FloCAD. The Thermal Desktop model includes an Air Revitalization System (ARS Loop), a Suit Loop, a Cabin Loop, and Pressure Control System (PCS) for supplying make-up gas (N2 and O2) to the Cabin and Suit Loop. The ARS and PCS are designed to maintain air quality at acceptable O2, CO2 and humidity levels as well as internal pressures in the vehicle Cabin and during suited operations. This effort required development of a suite of Thermal Desktop Orion ECLSS models to address the need for various simulation capabilities regarding ECLSS performance. An initial highly detailed model of the ARS Loop was developed in order to simulate rapid pressure transients (water hammer effects) within the ARS Loop caused by events such as cycling of the Pressurized Swing Adsorption (PSA) Beds and required high temporal resolution (small time steps) in the model during simulation. A second ECLSS model was developed to simulate events which occur over longer periods of time (over 30 minutes) where O2, CO2 and humidity levels, as well as internal pressures needed to be monitored in the cabin and for suited operations. Stand-alone models of the PCS and the Negative Pressure relief Valve (NPRV) were developed to study thermal effects within the PCS during emergency scenarios (Cabin Leak) and cabin pressurization during vehicle re-entry into Earth's atmosphere. Results from the Orion ECLSS models were used during Orion Delta-PDR (July, 2014) to address Key Design Requirements (KDR's) for Suit Loop operations for multiple mission scenarios.

On the relationship between magnetic cancellation and UV burst formation

NASA Astrophysics Data System (ADS)

Nelson, C. J.; Doyle, J. G.; Erdélyi, R.

2016-12-01

Burst-like events with signatures in the UV are often observed co-spatial to strong line-of-sight photospheric magnetic fields. Several authors, for example, have noted the spatial relationship between Ellerman bombs (EBs) and moving magnetic features (MMFs), regions of flux which disconnect from a sunspot or pore before propagating away in the moat flow and often displaying evidence of cancellation. In this article, data collected by the Solar Dynamics Observatory's Helioseismic and Magnetic Imager and Atmospheric Imaging Assembly are analysed in an attempt to understand the potential links between such cancellation and UV burst formation. Two MMFs from AR 11579, three bi-poles from AR 11765, and six bi-poles (four of which were co-spatial to Interface Region Imaging Spectrograph bursts) in AR 11850 were identified for analysis. All of these cancellation features were found to have lifetimes of the order hours and cancellation rates of the order 1014-1015 Mx s-1. Hα line wing data from the Dunn Solar Telescope's Interferometric BIdimensional Spectrometer were also available for AR 11579 facilitating a discussion of links between MMFs and EBs. Using an algebraic model of photospheric magnetic reconnection, the measured cancellation rates are then used to ascertain estimates of certain quantities (such as upflow speeds, jet extents, and potential energy releases), which compared reasonably to the properties of EBs reported within the literature. Our results suggest that cancellation rates of the order measured here are capable of supplying enough energy to drive certain UV bursts (including EBs), however, they are not a guaranteeing condition for burst formation.

Numerical and experimental investigations for the evaluation of the wear coefficient of reverse total shoulder prostheses.

PubMed

Mattei, Lorenza; Di Puccio, Francesca; Joyce, Thomas J; Ciulli, Enrico

2015-03-01

In the present study, numerical and experimental wear investigations on reverse total shoulder arthroplasties (RTSAs) were combined in order to estimate specific wear coefficients, currently not available in the literature. A wear model previously developed by the authors for metal-on-plastic hip implants was adapted to RTSAs and applied in a double direction: firstly, to evaluate specific wear coefficients for RTSAs from experimental results and secondly, to predict wear distribution. In both cases, the Archard wear law (AR) and the wear law of UHMWPE (PE) were considered, assuming four different k functions. The results indicated that both the wear laws predict higher wear coefficients for RTSA with respect to hip implants, particularly the AR law, with k values higher than twofold the hip ones. Such differences can significantly affect predictive wear model results for RTSA, when non-specific wear coefficients are used. Moreover, the wear maps simulated with the two laws are markedly different, although providing the same wear volume. A higher wear depth (+51%) is obtained with the AR law, located at the dome of the cup, while with the PE law the most worn region is close to the edge. Taking advantage of the linear trend of experimental volume losses, the wear coefficients obtained with the AR law should be valid despite having neglected the geometry update in the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of OASIS QSAR Models Using ToxCast™ in Vitro Estrogen and Androgen Receptor Binding Data and Application in an Integrated Endocrine Screening Approach

PubMed Central

Bhhatarai, Barun; Wilson, Daniel M.; Price, Paul S.; Marty, Sue; Parks, Amanda K.; Carney, Edward

2016-01-01

Background: Integrative testing strategies (ITSs) for potential endocrine activity can use tiered in silico and in vitro models. Each component of an ITS should be thoroughly assessed. Objectives: We used the data from three in vitro ToxCast™ binding assays to assess OASIS, a quantitative structure-activity relationship (QSAR) platform covering both estrogen receptor (ER) and androgen receptor (AR) binding. For stronger binders (described here as AC50 < 1 μM), we also examined the relationship of QSAR predictions of ER or AR binding to the results from 18 ER and 10 AR transactivation assays, 72 ER-binding reference compounds, and the in vivo uterotrophic assay. Methods: NovaScreen binding assay data for ER (human, bovine, and mouse) and AR (human, chimpanzee, and rat) were used to assess the sensitivity, specificity, concordance, and applicability domain of two OASIS QSAR models. The binding strength relative to the QSAR-predicted binding strength was examined for the ER data. The relationship of QSAR predictions of binding to transactivation- and pathway-based assays, as well as to in vivo uterotrophic responses, was examined. Results: The QSAR models had both high sensitivity (> 75%) and specificity (> 86%) for ER as well as both high sensitivity (92–100%) and specificity (70–81%) for AR. For compounds within the domains of the ER and AR QSAR models that bound with AC50 < 1 μM, the QSAR models accurately predicted the binding for the parent compounds. The parent compounds were active in all transactivation assays where metabolism was incorporated and, except for those compounds known to require metabolism to manifest activity, all assay platforms where metabolism was not incorporated. Compounds in-domain and predicted to bind by the ER QSAR model that were positive in ToxCast™ ER binding at AC50 < 1 μM were active in the uterotrophic assay. Conclusions: We used the extensive ToxCast™ HTS binding data set to show that OASIS ER and AR QSAR models had high sensitivity and specificity when compounds were in-domain of the models. Based on this research, we recommend a tiered screening approach wherein a) QSAR is used to identify compounds in-domain of the ER or AR binding models and predicted to bind; b) those compounds are screened in vitro to assess binding potency; and c) the stronger binders (AC50 < 1 μM) are screened in vivo. This scheme prioritizes compounds for integrative testing and risk assessment. Importantly, compounds that are not in-domain, that are predicted either not to bind or to bind weakly, that are not active in in vitro, that require metabolism to manifest activity, or for which in vivo AR testing is in order, need to be assessed differently. Citation: Bhhatarai B, Wilson DM, Price PS, Marty S, Parks AK, Carney E. 2016. Evaluation of OASIS QSAR models using ToxCast™ in vitro estrogen and androgen receptor binding data and application in an integrated endocrine screening approach. Environ Health Perspect 124:1453–1461; http://dx.doi.org/10.1289/EHP184 PMID:27152837

40Ar/36Ar analyses of historic lava flows

USGS Publications Warehouse

Dalrymple, G.B.

1969-01-01

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

Population pharmacokinetics and pharmacodynamics of ticagrelor and AR-C124910XX in Chinese healthy male subjects.

PubMed

Liu, Shuaibing; Xue, Ling; Shi, Xiangfen; Sun, Zhiyong; Zhu, Zhenfeng; Zhang, Xiaojian; Tian, Xin

2018-06-01

Ticagrelor, the first reversible P2Y 12 receptor antagonist, exhibits faster onset and offset of antiplatelet effects and more consistent platelet inhibition than clopidogrel in both healthy subjects and patients with stable coronary artery disease. The objectives of this study were to establish a population pharmacokinetics (PK) and pharmacodynamics (PD) model of ticagrelor and to provide a theoretical basis for the optimization of ticagrelor treatment in clinic. A single oral dose of 180 mg ticagrelor was administered to 14 healthy male subjects in a randomized study. Common single-nucleotide polymorphisms (SNPs) in biotransformation enzymes CYP3A4 and CYP3A5 (CYP3A4*1G and CYP3A5*3) were genotyped by PCR-direct sequencing. Blood samples were collected to measure plasma concentrations of ticagrelor and its active metabolite AR-C124910XX and maximal platelet inhibition. Various models were evaluated to characterize the pharmacokinetics of ticagrelor and AR-C124910XX as well as their PK-PD relationship. Covariates that may potentially affect PK or PD of ticagrelor and AR-C124910XX were included and assessed. Simulation for dosage regimen was performed based on the final PK-PD model. Ticagrelor and AR-C124910XX PK were best described by a two-compartment model with first-order transit absorption model. CYP3A4*1G increased clearance for AR-C124910XX, but had no significant effect on ticagrelor clearance. The relationship between concentration and platelet response of ticagrelor was best described by a turnover model. Simulation results indicated that a lower dosage regimen of 30 mg maintenance dose (MD) could produce an anticipated anti-platelet response in comparison to the routine clinical dosage regimen (180 mg loading dose (LD), 90 mg MD). Our study developed a population PK-PD model for ticagrelor and further simulation for dosage regimen was performed based on the final model. Compared to the current recommended dosage regimen (180 mg LD, 90 mg MD), our simulation result of a relatively lower dose (30 mg MD) could also obtain an acceptable anti-platelet response, which may provide a reference for further dosage regimen design in Chinese population.

Temporal variations in the cooling and denudation history of the Hunza plutonic complex, Karakoram Batholith, revealed by 40Ar/39Ar thermochronology

NASA Astrophysics Data System (ADS)

Krol, Michael A.; Zeitler, Peter K.; Poupeau, GéRard; Pecher, Arnaud

1996-04-01

The 40Ar/39Ar thermochronology of the Late Cretaceous Hunza plutonic complex reveals an episodic cooling and denudation history for this regional-scale pluton. The 40Ar/39Ar analyses of biotites from a vertical relief section of >3200 m reveal a pulse of rapid cooling at ˜20 Ma. In the interval of 110-27 Ma, age-elevation distributions suggest denudation rates of the order of 0.02 ± 0.003 mm/yr. At ˜20 Ma, denudation rates increased significantly to 2.7 ± 0.7 mm/yr, then returned to much slower rates until 12 Ma. A second pulse of rapid cooling beginning at 12 Ma is revealed by inverse numerical modeling of multidiffusion domain alkali feldspars from a vertical section of 1700 m. Decreasing in elevation, these samples record the onset of rapid cooling at 12, 9, and 7 Ma, respectively. All of the alkali feldspars record a period of nearly isothermal conditions prior to the onset of rapid cooling when rates increased to 30°C/m.y. Assuming a geothermal gradient of 30°C/km, these cooling rates translate into denudation rates of 1.0 mm/yr. Apatite fission track analysis indicates denudation rates of 0.7 ± 0.1 mm/yr over the interval of 6.6 Ma to 2.4 Ma in agreement with the alkali feldspar data. These data suggest denudation of 2.9 ± 0.4 km since the Plio-Pleistocene. Together, the alkali feldspar and apatite data indicate that a minimum of 10 km of overburden has been removed since the mid-late Miocene. An electronic supplement of this material may be obtained on a diskette or Anonymous FTP from KOSMOS.AGU.ORG. (LOGIN to AGU's FTP account using ANONYMOUS as the username and GUEST as the password. Go to the right directory by typing CD APEND. Type LS to see what files are available. Type GET and the name of the file to get it. Finally, type EXIT to leave the system).(Paper 95TC02424, Temporal variations in the cooling and denudation history of the Hunza plutonic complex, Karakoram Batholith, revealed by 40Ar/39Ar thermochronology, M.A. Krol, P.K. Zeitler, G. Poupeau, and A. Pecher). Diskette may be ordered from American Geophysical Union, 2000 Florida Avenue, N.W., Washington, DC 20009; $15.00. Payment must accompany order.

Azo compound degradation kinetics and halonitromethane formation kinetics during chlorination.

PubMed

Fu, Jing; Wang, Xiaomao; Bai, Weiliang; Yang, Hongwei; Xie, Yuefeng F

2017-05-01

The chlorination of azo compounds can produce halonitromethanes (HNMs), which have attracted increasing concern due to their high genotoxicity. By impacting the speciation of chlorine and azo compounds, pH impacts apparent second-order rate constants of Methyl Orange (MO, 27.5-1.4 × 10 3  M -1  s -1 ), Acid Orange II (AO, 16.7-99.3 M -1  s -1 ), and Acid Red 1 (AR 1, 3.7-72.5 M -1  s -1 ) (pH range 6.3-9.0). The two-compartment first-order model successfully described the chloropicrin (TCNM) formation kinetics, suggesting that both fast- and slow-reacting precursors of TCNM are generated from the chlorination of azo compounds. The ratios between fast and slow formation rate constants for MO and AO were 15.6-5.4 × 10 2 , while that of AR 1 was 9.8-19.4 (pH range 6.5-9.0). The fraction of the fast-reacting TCNM precursors decreased with increasing pH for MO and AO; while that for AR 1 decreased when pH increased from 6.5 to 8.0, and then increased when pH increased from 8.0 to 9.0. The impact of pH on TCNM formation was also precursor-specific. The highest molar yields of TCNM predicted from the model in this study were 2.4%, 2.5%, and 1.5% for MO, AO, and AR 1, respectively. The study demonstrates that azo compounds are important HNM precursors, and pose a potential threat to drinking water safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microwave-assisted preparation of nitrogen-doped biochars by ammonium acetate activation for adsorption of acid red 18

NASA Astrophysics Data System (ADS)

Wang, Li; Yan, Wei; He, Chi; Wen, Hang; Cai, Zhang; Wang, Zixuan; Chen, Zhengzheng; Liu, Weifeng

2018-03-01

Nitrogen-doped biochars derived from Phragmites australis (PA) were prepared using ammonium chloride (AC) and ammonium acetate (AA) as nitrogen sources by phosphoric acid activation via microwave assisted treatment. Their physicochemical properties, acid red 18 (AR18) adsorption performance and possible mechanisms were systematically evaluated. Nitrogen was successfully doped onto the biochar's surface in the formation of pyrrole-N, pyridine-N and oxidized-N with pyridine-N being the major component (64%). The pHiep and basic foundational groups of the biochars increased consequently however their surface areas slightly decreased. The adsorption kinetic data were best fit to the pseudo-second order model and the equilibrium data were well simulated by Freundlich model for all biochars, indicating the important role of chemical interactions. The maximum AR18 adsorption capacities of PAB-AA and PAB-AC were 1.41 and 1.18 times higher compared with the non N-doped biochar, which were mainly attributed to the π-π EDA interaction between the pyridine-N and AR18 as revealed by the comparison of XPS analyses before and after AR18 adsorption. Meanwhile, other mechanisms such as pore filling effect, Lewis acid-base interaction, electrostatic attraction and hydrogen bonding also existed as demonstrated by BET, XPS and FTIR analyses.

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.

Energetics, structure and photodissociation dynamics of the cluster Arter dot N sup + sub 2

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

Kim, H.; Bowers, M.T.

A mass selected ion beam of ArN{sup +}{sub 2} clusters is brought to a spatial focus and crossed with the polarized output of an argon ion laser. Photofragment ions are mass and energy analyzed using an electrostatic analyzer and detected using single ion counting methods. Photoproducts observed over the photon energy range of 2.1 to 3.5 eV are Ar{sup +}/N{sub 2} and N{sup +}{sub 2}/Ar with the former favored by about a factor of 3. Analysis of the data indicate the upper state is purely repulsive leading to strongly translationally and vibrationally excited products. The absolute cross section has anmore » onset at about 600 nm and smoothly increases to 357 nm. In order to reasonably interpret the data it is suggested the higher energy Ar{sup +}({sup 2}{ital P}{sub 3/2})/N{sub 2} asymptote diabatically correlates to the ground state of ArN{sup +}{sub 2} and the lower energy N{sup +}{sub 2}({ital X} {sup 2}{Sigma})/Ar asymptote diabatically correlates to the repulsive state accessed by the photon. Detailed dynamics in the region where the curves cross are responsible for the observed product distribution. Application of an impulsive model indicates the ground state of ArN{sup +}{sub 2} is linear. Finally, equilibrium measurements of the reaction (N{sub 2}){sup +}{sub 2}+Ar{leftrightarrow}ArN{sup +}{sub 2}+N{sub 2} indicate {Delta}{ital H}{sup 0}{sub 0}={minus}1.0{plus minus}0.3 kcal/mol and {Delta}{ital S}{sup 0}=1.5{plus minus}0.5 cal k{sup {minus}1} mol{sup {minus}1} in agreement with the result of Teng and Conway which had been disputed in the literature.« less

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

PubMed

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.

Ti diffusion in ion prebombarded MgO(100). I. A model for quantitative analysis

NASA Astrophysics Data System (ADS)

Lu, M.; Lupu, C.; Styve, V. J.; Lee, S. M.; Rabalais, J. W.

2002-01-01

Enhancement of Ti diffusion in MgO(100) prebombarded with 7 keV Ar+ has been observed. Diffusion was induced by annealing to 1000 °C following the prebombardment and Ti evaporation. Such a sample geometry and experimental procedure alleviates the continuous provision of freely mobile defects introduced by ion irradiation during annealing for diffusion, making diffusion proceed in a non-steady-state condition. Diffusion penetration profiles were obtained by using secondary ion mass spectrometry depth profiling techniques. A model that includes a depth-dependent diffusion coefficient was proposed, which successfully explains the observed non-steady-state radiation enhanced diffusion. The diffusion coefficients are of the order of 10-20 m2/s and are enhanced due to the defect structure inflected by the Ar+ prebombardment.

Photospheric Current Spikes as Possible Predictors of Flares

NASA Technical Reports Server (NTRS)

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

2016-01-01

Flares involve generation of the largest current densities in the solar atmosphere. This suggests the hypothesis that prior to a large (M,X) flare there are related time dependent changes in the photospheric current distribution, and hence in the resistive heating rate in neutral line regions (NLRs). If this is true, these changes might be useful predictors of flares. Preliminary evidence supporting this hypothesis is presented. Results from a data driven, near photospheric, 3D magnetohydrodynamic type model suggest the model might be useful for predicting M and X flares several hours to several days in advance. The model takes as input the photospheric magnetic field observed by the Helioseismic and Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. The model computes quantities in every active region (AR) pixel for 14 ARs, with spurious Doppler periods due to SDO orbital motion filtered out of the time series of the magnetic field for each pixel. Spikes in the NLR resistive heating rate Q, appearing as increases by orders of magnitude above background values in the time series of Q are found to occur, and appear to be correlated with the occurrence of M or X flares a few hours to a few days later. The subset of spikes analyzed at the pixel level are found to occur on HMI and granulation scales of 1 arcsec and 12 minutes. Spikes are found in NLRs with and without M or X flares, and outside as well as inside NLRs, but the largest spikes are localized in the NLRs of ARs with M or X flares, and associated with horizontal magnetic field strengths approximately several hG, and vertical magnetic field strengths several orders of magnitude smaller. The spikes may be signatures of horizontal current sheets associated with emerging magnetic flux.

Photospheric Current Spikes as Possible Predictors of Flares

NASA Technical Reports Server (NTRS)

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

2016-01-01

Flares involve generation of the largest current densities in the solar atmosphere. This suggests the hypothesis that prior to a large (M,X) flare there are related time dependent changes in the photospheric current distribution, and hence in the resistive heating rate in neutral line regions (NLRs). If this is true, these changes might be useful predictors of flares. Evidence supporting this hypothesis is presented. Results from a data driven, near photospheric, 3D magnetohydrodynamic type model suggest the model might be useful for predicting M and X flares several hours to several days in advance. The model takes as input the photospheric magnetic field observed by the Helioseismic & Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. The model computes quantities in every active region (AR) pixel for 14 ARs, with spurious Doppler periods due to SDO orbital motion filtered out of the time series of the magnetic field for each pixel. Spikes in the NLR resistive heating rate Q, appearing as increases by orders of magnitude above background values in the time series of Q are found to occur, and appear to be correlated with the occurrence of M or X flares a few hours to a few days later. The subset of spikes analyzed at the pixel level are found to occur on HMI and granulation scales of 1 arcsec and 12 minutes. Spikes are found in NLRs with and without M or X flares, and outside as well as inside NLRs, but the largest spikes are localized in the NLRs of ARs with M or X flares, and associated with horizontal magnetic field strengths several hG, and vertical magnetic field strengths several orders of magnitude smaller, suggesting that the spikes are associated with current sheets.

Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells

PubMed Central

Chang, Chawnshang; Yeh, Shuyuan; Lee, Soo Ok; Chang, Ta-min

2013-01-01

The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases. PMID:24653668

Uncertainties in Projecting Future Changes in Atmospheric Rivers and Their Impacts on Heavy Precipitation over Europe

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

Gao, Yang; Lu, Jian; Leung, L. Ruby

This study investigates the North Atlantic atmospheric rivers (ARs) making landfall over western Europe in the present and future climate from the multi-model ensemble of the Coupled Model Intercomparison Project Phase 5 (CMIP5). Overall, CMIP5 captures the seasonal and spatial variations of historical landfalling AR days, with the large inter-model variability strongly correlated with the inter-model spread of historical jet position. Under RCP 8.5, AR frequency is projected to increase a few times by the end of this century. While thermodynamics plays a dominate role in the future increase of ARs, wind changes associated with the midlatitude jet shifts alsomore » significantly contribute to AR changes, resulting in dipole change patterns in all seasons. In the North Atlantic, the model projected jet shifts are strongly correlated with the simulated historical jet position. As models exhibit predominantly equatorward biases in the historical jet position, the large poleward jet shifts reduce AR days south of the historical mean jet position through the dynamical connections between the jet positions and AR days. Using the observed historical jet position as an emergent constraint, dynamical effects further increase AR days in the future above the large increases due to thermodynamical effects. In the future, both total and extreme precipitation induced by AR contribute more to the seasonal mean and extreme precipitation compared to present primarily because of the increase in AR frequency. While AR precipitation intensity generally increases more relative to the increase in integrated vapor transport, AR extreme precipitation intensity increases much less.« 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

76 FR 11547 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... interest rates and descriptive information about Auction Rate Securities (``ARS'') and Variable Rate Demand... interest rate setting mechanisms for ARS and liquidity facilities for VRDOs, information about orders submitted for an ARS auction, and additional information about VRDOs.\\4\\ To provide subscribers with access...

75 FR 52793 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

... the MSRB on municipal Auction Rate Securities (``ARS'') and Variable Rate Demand Obligations (``VRDOs... information currently collected and made transparent by the MSRB on municipal Auction Rate Securities (``ARS... that define auction procedures and interest rate setting mechanisms for ARS and liquidity facilities...

Scaling analysis and model estimation of solar corona index

NASA Astrophysics Data System (ADS)

Ray, Samujjwal; Ray, Rajdeep; Khondekar, Mofazzal Hossain; Ghosh, Koushik

2018-04-01

A monthly average solar green coronal index time series for the period from January 1939 to December 2008 collected from NOAA (The National Oceanic and Atmospheric Administration) has been analysed in this paper in perspective of scaling analysis and modelling. Smoothed and de-noising have been done using suitable mother wavelet as a pre-requisite. The Finite Variance Scaling Method (FVSM), Higuchi method, rescaled range (R/S) and a generalized method have been applied to calculate the scaling exponents and fractal dimensions of the time series. Autocorrelation function (ACF) is used to find autoregressive (AR) process and Partial autocorrelation function (PACF) has been used to get the order of AR model. Finally a best fit model has been proposed using Yule-Walker Method with supporting results of goodness of fit and wavelet spectrum. The results reveal an anti-persistent, Short Range Dependent (SRD), self-similar property with signatures of non-causality, non-stationarity and nonlinearity in the data series. The model shows the best fit to the data under observation.

Mass Ejection from Old and Young Stars and the Sun

NASA Astrophysics Data System (ADS)

Jatenco-Pereira, V.; Opher, R.

1990-11-01

RESUMEN. Para poder explicar: 1) la enorme cantidad de perdida de masa y la baja velocidad asint5tica de las estrellas gigantes de o, y 2) los flujos de masa observados en protoestrellas, se sugiere un modelo para Ia perdida de masa, en donde se usa un flujo de ondas de Alfvencomo un mecanismo de aceleraci6n para los vientos de estrellas de tipo y vientos en protoestrellas. Se estudian los mecanismos de disipaci5n de las ondas de Alfven: los amortiguamientos no lineal, de superficie reso- nante y turbulento. En nuestro modelo se usa una divergente A(r) = A(R0) (r/r0)5 (donde A(r) es el area a una distancia radial r, y (A(r)/r2)max/(A(ro)/r02 - 10). Tambien se sugiere un modelo para una de hoyo coronal en el Sol. Se muestra que para satisfacer los datos observacionales en el Sol, tomando en cuenta la deposici6n del momento de las ondas de Alfven sobre el viento, se necesita: (a) una divergencia lenta en un hoyo coronal hasta una altura de 0.01 - 0.1 R seguido de (b) una divergencia rap ida de hasta una altura aproximada de 1 R . ABSTRACT: In order to explain (1) a large mass-loss rate and a small asymptotic flow speed of late-type giant stars and (2) the observed protostellar mass outflows, we suggest a model for mass loss, where we use a flux of Alfven waves as a mechanism of acceleration for late-type giant star winds and protostellar winds. We study the Alfven wave dissipation mechanisms: nonlinear damping, resonant surface damping, and turbulent damping. In our model we use a diverging geometry A(r) = A(r0) (r I r )S (where A(r) is the cross sectional area of the geometry at a radial distance r, and(A(r) I r2)max/(A(r0)/r02) = 10). We also suggest a model for a coronal hole geometry in the sun. We show that in order to satisfy the observational data of the sun, taking into account Alfven wave momentum deposition in the wind, we need: (a) a slow divergence in a coronal hole up t6 a height of 0.01 - 0.1 followed by (b) a rapid divergence up to a height of approximately 1 Re Key : '? #TICS - STARS-LATE TYPE - STARS- LOSS

A brief overview of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx) database and campaign operation centre (ChOC)

NASA Astrophysics Data System (ADS)

Ferré, Hélène; Dulac, François; Belmahfoud, Nizar; Brissebrat, Guillaume; Cloché, Sophie; Descloitres, Jacques; Fleury, Laurence; Focsa, Loredana; Henriot, Nicolas; Ramage, Karim; Vermeulen, Anne

2016-04-01

Initiated in 2010 in the framework of the multidisciplinary research programme MISTRALS (Mediterranean Integrated Studies at Regional and Local Scales; http:www.mistrals-home.org), the Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr/) aims at federating the scientific community for an updated 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 project combines mid- and long-term monitoring, intensive field campaigns, use of satellite data, and modelling studies. In this presentation we provide an overview of the campaign operation centre (http://choc.sedoo.fr/) and project database (http://mistrals.sedoo.fr/ChArMEx), at the end of the first experimental phase of the project that included a series of large campaigns based on airborne means (including balloons and various aircraft) and a network of surface stations. Those campaigns were performed mainly in the western Mediterranean basin in the summer of 2012, 2013 and 2014 with the help of the ChArMEx Operation Centre (ChOC), an open web site that has the objective to gather and display daily quick-looks from model forecasts and near-real time in situ and remote sensing observations of physical and chemical weather conditions relevant for the everyday campaign operation decisions. The ChOC is also useful for post campaign analyses and can be completed with a number of quick-looks of campaign results obtained later in order to offer an easy access to, and comprehensive view of all available data during the campaign period. The items included are selected according to the objectives and location of the given campaigns. The second experimental phase of ChArMEx from 2015 on is more focused on the eastern basin. In addition, the project operation centre is planned to be adapted for a joint MERMEX-ChArMEx oceanographic cruise (PEACETIME) for a study at the air-sea interface focused on the biogeochemical impact of atmospheric deposition. The database includes a wide diversity of data and parameters relevant to atmospheric chemistry. The objective of the database task team is to organize data management, distribution system and services, such as facilitating the exchange of information and stimulating the collaboration between researchers within the ChArMEx community, and beyond. The database relies on a strong collaboration between ICARE, IPSL and OMP data centers and has been set up in the framework of the MISTRALS programme data portal. ChArMEx data, either produced or used by the project, are documented and made easily accessible through the database website, which offers expected user-friendly functionalities: data catalog, user registration procedure, search tool to select and access data based on parameters, instruments, countries, platform or project, information of dataset PIs about downloadings... The metadata (data description) are standardized, and comply with international standards (ISO 19115-19139; INSPIRE European Directive; Global Change Master Directory Thesaurus). A Digital Object Identifier (DOI) assignement procedure allows to automatically register the datasets, in order to make them easier to access, cite, reuse and verify. At present, the ChArMEx database contains about 160 datasets, including more than 120 in situ datasets (from a total of 7 campaigns and various monitoring stations including the background atmospheric station of Ersa (June 2012-July 2014), 30 model output sets (dust model intercomparison, MEDCORDEX scenarios...), a high resolution emission inventory over the Mediterranean made available as part of the ECCAD database (http://eccad.sedoo.fr/eccad_extract_interface/JSF/page_charmex.jsf), etc. Some in situ datasets have been inserted in a relational database in order to enable more accurate selection and download of different datasets in a shared format. Many dedicated satellite products (SEVIRI, TRIMM, PARASOL...) are processed and will soon be accessible through the database website. Every scientist is welcome to visit the ChArMEx websites, to register and request data, and to contact charmex-database@sedoo.fr for any question.

A statistical model for predicting muscle performance

NASA Astrophysics Data System (ADS)

Byerly, Diane Leslie De Caix

The objective of these studies was to develop a capability for predicting muscle performance and fatigue to be utilized for both space- and ground-based applications. To develop this predictive model, healthy test subjects performed a defined, repetitive dynamic exercise to failure using a Lordex spinal machine. Throughout the exercise, surface electromyography (SEMG) data were collected from the erector spinae using a Mega Electronics ME3000 muscle tester and surface electrodes placed on both sides of the back muscle. These data were analyzed using a 5th order Autoregressive (AR) model and statistical regression analysis. It was determined that an AR derived parameter, the mean average magnitude of AR poles, significantly correlated with the maximum number of repetitions (designated Rmax) that a test subject was able to perform. Using the mean average magnitude of AR poles, a test subject's performance to failure could be predicted as early as the sixth repetition of the exercise. This predictive model has the potential to provide a basis for improving post-space flight recovery, monitoring muscle atrophy in astronauts and assessing the effectiveness of countermeasures, monitoring astronaut performance and fatigue during Extravehicular Activity (EVA) operations, providing pre-flight assessment of the ability of an EVA crewmember to perform a given task, improving the design of training protocols and simulations for strenuous International Space Station assembly EVA, and enabling EVA work task sequences to be planned enhancing astronaut performance and safety. Potential ground-based, medical applications of the predictive model include monitoring muscle deterioration and performance resulting from illness, establishing safety guidelines in the industry for repetitive tasks, monitoring the stages of rehabilitation for muscle-related injuries sustained in sports and accidents, and enhancing athletic performance through improved training protocols while reducing injury.

The effect of thermal resetting and recrystallisation on white mica 40Ar/39Ar ages during retrograde metamorphism on Syros, Greece

NASA Astrophysics Data System (ADS)

Uunk, Bertram; Wijbrans, Jan; Brouwer, Fraukje

2015-04-01

White mica 40Ar/39Ar dating is a proven powerful tool for constraining timing of metamorphism, deformation and exhumation. However, in high-pressure metamorphic rocks, dating often results in wide age ranges which are not in agreement with constraints from other isotopic systems, indicating that geological and chemical processes complicate straightforward 40Ar/39Ar dating. In this research project, white mica ages from rocks of the Cycladic Blueschist Unit on Syros, Greece with contrasting rheology and strain mechanisms are compared, in order to better understand the role of deformation, recrystallization and fluid flow on 40Ar/39Ar ages of white mica during retrograde metamorphism. Resulting ages vary along different sections on the island, inconsistent with other isotopic constraints on eclogite-blueschist metamorphism (55-50 Ma) and greenschist overprinting (41-30 Ma). Two end-member models are possible: 1) Results represent continuous crystallization of white mica while moving from blueschist to greenschist conditions in the metamorphic P-T loop, or 2) white mica equilibrated in eclogite-blueschist conditions and their diffusion systematics were progressively perturbed during greenschist overprinting. The single grain fusion analyses yielded contrasting age distributions, which indicate contrasts in degree of re-equilibration during retrograde metamorphism. Step wise heating of larger grain populations resulted in flat plateau shapes, providing no evidence for partial resetting. Electron microprobe measurements of Si per formula unit, as a proxy for pressure during crystallisation, do not explain age variation within sections or on the island scale. The previously unreported north-south age trend and age ranges per sample, as shown only in the 40Ar/39Ar system of the metapelitic and marble lithologies, contains key information that will allow us to test between different scenarios for age formation. Excess argon infiltration at this stage seems to have been of minor importance. Our new approach should lead to a better understanding of the interplay of these processes during and after HP metamorphism.

Comparison of Adsorption/Desorption of Volatile Organic Compounds (VOCs) on Electrospun Nanofibers with Tenax TA for Potential Application in Sampling

PubMed Central

Chu, Lanling; Deng, Siwei; Zhao, Renshan; Deng, Jianjun; Kang, Xuejun

2016-01-01

The objective of this study was to compare the adsorption/desorption of target compounds on homemade electrospun nanofibers, polystyrene (PS) nanofibers, acrylic resin (AR) nanofibers and PS-AR composite nanofibers with Tenax TA. Ten volatile organic compounds (VOCs) were analyzed by preconcentration onto different sorbents followed by desorption (thermal and solvent orderly) and analysis by capillary gas chromatography. In comparison to Tenax TA, the electrospun nanofibers displayed a significant advantage in desorption efficiency and adsorption selectivity. Stability studies were conducted as a comparative experiment between PS-AR nanofibers and Tenax TA using toluene as the model compound. No stability problems were observed upon storage of toluene on both PS-AR nanofibers and Tenax TA over 60 hours period when maintained in an ultra-freezer (−80°C). The nanofibers provided slightly better stability for the adsorbed analytes than Tenax TA under other storage conditions. In addition, the nanofibers also provided slightly better precision than Tenax TA. The quantitative adsorption of PS-AR nanofibers exhibited a good linearity, as evidenced by the 0.988–0.999 range of regression coefficients (R). These results suggest that for VOCs sampling the electrospun nanofibers can be a potential ideal adsorbent. PMID:27776140

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

PubMed

Albadarin, Ahmad B; Mangwandi, Chirangano

2015-12-01

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

Photospheric Current Spikes And Their Possible Association With Flares - Results from an HMI Data Driven Model

NASA Astrophysics Data System (ADS)

Goodman, M. L.; Kwan, C.; Ayhan, B.; Eric, S. L.

2016-12-01

A data driven, near photospheric magnetohydrodynamic model predicts spikes in the horizontal current density, and associated resistive heating rate. The spikes appear as increases by orders of magnitude above background values in neutral line regions (NLRs) of active regions (ARs). The largest spikes typically occur a few hours to a few days prior to M or X flares. The spikes correspond to large vertical derivatives of the horizontal magnetic field. The model takes as input the photospheric magnetic field observed by the Helioseismic & Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. This 2.5 D field is used to determine an analytic expression for a 3 D magnetic field, from which the current density, vector potential, and electric field are computed in every AR pixel for 14 ARs. The field is not assumed to be force-free. The spurious 6, 12, and 24 hour Doppler periods due to SDO orbital motion are filtered out of the time series of the HMI magnetic field for each pixel. The subset of spikes analyzed at the pixel level are found to occur on HMI and granulation scales of 1 arcsec and 12 minutes. Spikes are found in ARs with and without M or X flares, and outside as well as inside NLRs, but the largest spikes are localized in the NLRs of ARs with M or X flares. The energy to drive the heating associated with the largest current spikes comes from bulk flow kinetic energy, not the electromagnetic field, and the current density is highly non-force free. The results suggest that, in combination with the model, HMI is revealing strong, convection driven, non-force free heating events on granulation scales, and it is plausible these events are correlated with subsequent M or X flares. More and longer time series need to be analyzed to determine if such a correlation exists.

Precipitation Phase Partitioning during Inland Penetrating Atmospheric River events: Role of Initial Land Surface Conditions

NASA Astrophysics Data System (ADS)

Rudisill, W. J.; Flores, A. N.; FitzGerald, K.; Masarik, M. T.

2017-12-01

In the Western US, the occurrence (or lack thereof) of a handful of cool-season Atmospheric River (AR) events exerts significant controls on the seasonal water budget in many watersheds. The occurrence of these ARs can serve to alleviate drought and can also lead to significant flooding. In winter seasons, ARs typically bring warmer than average conditions and both rain and snow. To date, there has been little effort to understand how the land surface hydrological states prior to and during the arrival of ARs, acting on the surface water and energy balance, impact the onset, extent, and evolution of precipitation intensity and phase during AR events. While precipitation arriving as snow can contribute to seasonal snowpacks that lead to runoff later in hot/dry seasons, liquid precipitation can contribute to more rapid runoff or deplete existing snowpacks. The latter case, in which latent and advected heat from fallen rain causes snowmelt, is a key mechanism of flood and landslide-producing runoff in the Western United States. Motivated by an extensive, flood producing AR in 2010, we examine the sensitivity of hydrometeor phase to land surface forcings (sensible/latent heating, short/longwave radiation) using the WRF (Weather Research and Forecasting) model in Central Idaho. Specifically, we evaluate whether pre-existing snow covered area extent, snow water equivalent (SWE), and cold-content influence the partitioning of precipitation into solid and liquid phases during inland AR events. Our experimental design leverages a long-term coupled land-atmosphere simulation with WRF over the study domain in order to evaluate how a set of particular AR events evolve when exposed to initial land surface states capturing a broad range of climatological conditions during the past 30 years.

Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

PubMed

Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

2018-03-28

ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

An experimental study on amelioration of dyslipidemia-induced atherosclesis by Clematichinenoside through regulating Peroxisome proliferator-activated receptor-α mediated apolipoprotein A-I, A-II and C-III.

PubMed

Liu, Chao; Guo, Qianqian; Lu, Mengchen; Li, Yunman

2015-08-15

Prevention or amelioration the prevalence of atherosclerosis has been an effective strategy in the management of cardiovascular diseases. The aim of the study was to scrutinize the effect of Clematichinenoside (AR) on dyslipidemia-induced atherosclerosis and explore its capability on expression of Peroxisome proliferator-activated receptor-α (PPAR-alpha), apolipoprotein A-I (APOA1) and A-II (APOA2), and suppression of apolipoprotein C-III (APOC3) genes and proteins. In the present study, we investigated atherosclerosis effect of AR using a combination of high-fat diet and balloon injury model in rabbits. The levels of biochemical indicators were evaluated in plasma, liver and HepG2 cells using immunoassay technology. In order to expose the underlying mechanism, we evaluated the regulation of PPAR-alpha, APOA1, APOA2 and APOC3 expressions by AR, and we further evaluated the interactions between them after transfection with shRNA (shPPAR-alpha) and, the action of PPAR-alpha in HepG2 cells. We could find that AR markedly promoted the PPAR-alpha transfer from cytoplasm to nucleus which resulted in the alteration of APOA1, APOA2 and APOC3 expressions in HepG2 cells. Moreover, AR significantly reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) levels, and elevated high-density lipoprotein cholesterol (HDL-C) level, which play an important role in dyslipidemia-induced atherosclerosis. In conclusion, AR ameliorated atherosclerosis via the regulation of hepatic lipid metabolism, and AR also contributed to the activation of PPAR-alpha, APOA1, APOA2 and APOC3. Therefore, AR could be a potential therapeutic agent in the treatment of atherosclerosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of mobile genetic elements in antibiotic resistant Salmonella enterica isolates from food animals

USDA-ARS?s Scientific Manuscript database

Antibiotic resistance (AR) is a major concern for the agricultural industry in the U.S. and globally. The problem of AR is further complicated by AR genes often being located on mobile genetic elements (MGEs) resulting in their spread among bacteria. In order to investigate the relationship between ...

77 FR 44555 - Partial Approval and Disapproval of Air Quality Implementation Plans; Arizona; State Board...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

.... ARS 49-478(B) establishes the compositional requirements of the county Air Quality Hearing Boards... County Code 17.04.190 (``Composition'') generally mirrors the language or ARS 49-478 but also includes... membership requirement of ARS 49-478 to interests in persons subject to enforcement orders. However, this...

Concentration of atomic hydrogen in a dielectric barrier discharge measured by two-photon absorption fluorescence

NASA Astrophysics Data System (ADS)

Dvořák, P.; Talába, M.; Obrusník, A.; Kratzer, J.; Dědina, J.

2017-08-01

Two-photon absorption laser-induced fluorescence (TALIF) was utilized for measuring the concentration of atomic hydrogen in a volume dielectric barrier discharge (DBD) ignited in mixtures of Ar, H2 and O2 at atmospheric pressure. The method was calibrated by TALIF of krypton diluted in argon at atmospheric pressure, proving that three-body collisions had a negligible effect on quenching of excited krypton atoms. The diagnostic study was complemented with a 3D numerical model of the gas flow and a zero-dimensional model of the chemistry in order to better understand the reaction kinetics and identify the key pathways leading to the production and destruction of atomic hydrogen. It was determined that the density of atomic hydrogen in Ar-H2 mixtures was in the order of 1021 m-3 and decreased when oxygen was added into the gas mixture. Spatially resolved measurements and simulations revealed a sharply bordered region with low atomic hydrogen concentration when oxygen was added to the gas mixture. At substoichiometric oxygen/hydrogen ratios, this H-poor region is confined to an area close to the gas inlet and it is shown that the size of this region is not only influenced by the chemistry but also by the gas flow patterns. Experimentally, it was observed that a decrease in H2 concentration in the feeding Ar-H2 mixture led to an increase in H production in the DBD.

Atmospheric Rivers in VR-CESM: Historical Comparison and Future Projections

NASA Astrophysics Data System (ADS)

McClenny, E. E.; Ullrich, P. A.

2016-12-01

Atmospheric rivers (ARs) are responsible for most of the horizontal vapor transport from the tropics, and bring upwards of half the annual precipitation to midlatitude west coasts. The difference between a drought year and a wet year can come down to 1-2 ARs. Such few events transform an otherwise arid region into one which supports remarkable biodiversity, productive agriculture, and booming human populations. It follows that such a sensitive hydroclimate feature would demand priority in evaluating end-of-century climate runs, and indeed, the AR subfield has grown significantly over the last decade. However, results tend to vary wildly from study to study, raising questions about how to best approach ARs in models. The disparity may result from any number of issues, including the ability for a model to properly resolve a precipitating AR, to the formulation and application of an AR detection algorithm. ARs pose a unique problem in global climate models (GCMs) computationally and physically, because the GCM horizontal grid must be fine enough to resolve coastal mountain range topography and force orographic precipitation. Thus far, most end-of-century projections on ARs have been performed on models whose grids are too coarse to resolve mountain ranges, causing authors to draw conclusions on AR intensity from water vapor content or transport alone. The use of localized grid refinement in the Variable Resolution version of NCAR's Community Earth System Model (VR-CESM) has succeeded in resolving AR landfall. This study applies an integrated water vapor AR detection algorithm to historical and future projections from VR-CESM, with historical ARs validated against NASA's Modern Era Retrospective-Analysis for Research and Applications. Results on end-of-century precipitating AR frequency, intensity, and landfall location will be discussed.

The ChArMEx database

NASA Astrophysics Data System (ADS)

Ferré, Hélène; Descloitres, Jacques; Fleury, Laurence; Boichard, Jean-Luc; Brissebrat, Guillaume; Focsa, Loredana; Henriot, Nicolas; Mastrorillo, Laurence; Mière, Arnaud; Vermeulen, Anne

2013-04-01

The Chemistry-Aerosol Mediterranean Experiment (ChArMEx, http://charmex.lsce.ipsl.fr/) aims 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 project includes long term monitoring of environmental parameters, intensive field campaigns, use of satellite data and modelling studies. Therefore ChARMEx scientists produce and need to access a wide diversity of data. In this context, the objective of the database task is to organize data management, distribution system and services such as facilitating the exchange of information and stimulating the collaboration between researchers within the ChArMEx community, and beyond. The database relies on a strong collaboration between OMP and ICARE data centres and falls within the scope of the Mediterranean Integrated Studies at Regional And Locals Scales (MISTRALS) program data portal. All the data produced by or of interest for the ChArMEx community will be documented in the data catalogue and accessible through the database website: http://mistrals.sedoo.fr/ChArMEx. The database website offers different tools: - A registration procedure which enables any scientist to accept the data policy and apply for a user database account. - Forms to document observations or products that will be provided to the database in compliance with metadata international standards (ISO 19115-19139; INSPIRE; Global Change Master Directory Thesaurus). - A search tool to browse the catalogue using thematic, geographic and/or temporal criteria. - Sorted lists of the datasets by thematic keywords, by measured parameters, by instruments or by platform type. - A shopping-cart web interface to order in situ data files. At present datasets from the background monitoring station of Ersa, Cape Corsica and from the 2012 ChArMEx pre-campaign are available. - A user-friendly access to satellite products (SEVIRI, TRIMM, PARASOL...) stored in the ICARE data archive using OpeNDAP protocole The website will soon propose new facilities. In particular, many in situ datasets will be homogenized and inserted in a relational database, in order to enable more accurate data selection and download of different datasets in a shared format. In order to meet the operational needs of the airborne and ground based observational teams during the ChArMEx 2012 pre-campaign and the 2013 experiment, a day-to-day quick look and report display website has been developed too: http://choc.sedoo.org. It offers a convenient way to browse weather conditions and chemical composition during the campaign periods.

Comparisons of low-intensity versus moderate-intensity combined aerobic and resistance training on body composition, muscle strength, and functional performance in older women.

PubMed

Shiotsu, Yoko; Yanagita, Masahiko

2018-06-01

This study aimed to examine the effects of exercise order of combined aerobic and low- or moderate-intensity resistance training into the same session on body composition, functional performance, and muscle strength in healthy older women. Furthermore, this study compared the effects of different (low- vs moderate-) intensity combined training. A total of 60 healthy older women (age 61-81 y) were randomly assigned to five groups that performed aerobic exercise before low-intensity resistance training (AR-L, n = 12) or after resistance training (RA-L, n = 12), performed aerobic exercise before moderate-intensity resistance training (AR-M, n = 12) or after resistance training (RA-M, n = 12), or nonintervention control conditions (CON, n = 12). Body composition, functional performance, and muscle strength were evaluated before and after the 10-week training. No effects of exercise order of combined aerobic and low- or moderate-intensity resistance training (AR-L vs RA-L, AR-M vs RA-M) were observed in body composition, functional performance, or muscle strength, whereas the effects of training intensity of combined training (AR-L vs AR-M, RA-L vs RA-M) were observed on functional performance. All combined trainings significantly increased muscle strength and gait ability (P < 0.01, respectively). Functional reach test significantly increased in the AR-M and RA-M groups (P < 0.01, respectively), and there were significant group differences between AR-L and AR-M (P = 0.002), RA-L and RA-M (P = 0.014). Preliminary findings suggest that combined aerobic and low- or moderate-intensity resistance training increases muscle strength and improves gait ability, regardless of the exercise order. Also, greater improvement in dynamic balance capacity, a risk factor associated with falling, is observed in moderate-intensity combined training.

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

Gray, D.C.; Tepermeister, I.; Sawin, H.H.

A multiple beam apparatus has been constructed to facilitate the study of ion-enhanced fluorine chemistry on undoped polysilicon and silicon dioxide surfaces by allowing the fluxes of fluorine (F) atoms and argon (Ar{sup +}) ions to be independently varied over several orders of magnitude. The chemical nature of the etching surfaces has been investigated following the vacuum transfer of the sample dies to an adjoining x-ray photoelectron spectroscopy facility. The etching {open_quotes}enhancement{close_quotes} effect of normally incident Ar{sup +} ions has been quantified over a wide range of ion energy through the use of Kaufman and electron cyclotron resonance-type ion sources.more » The increase in per ion etching yield of fluorine saturated silicon and silicon dioxide surfaces with increasing ion energy (E{sub ion}) was found to scale as (E{sub ion}{sup 1/2}-E{sub th}{sup 1/2}), where E{sub th} is the etching threshold energy for the process. Simple near-surface site occupation models have been proposed for the quantification of the ion-enhanced etching kinetics in these systems. Acceptable agreement has been found in comparison of these Ar{sup +}/F etching model predictions with similar Ar{sup +}/XeF{sub 2} studies reported in the literature, as well as with etching rate measurements made in F-based plasmas of gases such as SF{sub 6} and NF{sub 3}. 69 refs., 12 figs., 6 tabs.« less

Application of tripolar concentric electrodes and prefeature selection algorithm for brain-computer interface.

PubMed

Besio, Walter G; Cao, Hongbao; Zhou, Peng

2008-04-01

For persons with severe disabilities, a brain-computer interface (BCI) may be a viable means of communication. Lapalacian electroencephalogram (EEG) has been shown to improve classification in EEG recognition. In this work, the effectiveness of signals from tripolar concentric electrodes and disc electrodes were compared for use as a BCI. Two sets of left/right hand motor imagery EEG signals were acquired. An autoregressive (AR) model was developed for feature extraction with a Mahalanobis distance based linear classifier for classification. An exhaust selection algorithm was employed to analyze three factors before feature extraction. The factors analyzed were 1) length of data in each trial to be used, 2) start position of data, and 3) the order of the AR model. The results showed that tripolar concentric electrodes generated significantly higher classification accuracy than disc electrodes.

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

Zhu, Cheng; Tsuge, Masashi; Khriachtchev, Leonid, E-mail: leonid.khriachtchev@helsinki.fi

Experimental and theoretical studies of HXeI and HXeH molecules in Ar, Kr, and Xe matrices are presented. HXeI exhibits the H–Xe stretching bands at 1238.0 and 1239.0 cm{sup −1} in Ar and Kr matrices, respectively, that are blue-shifted from the HXeI band observed in a Xe matrix (1193 cm{sup −1}) by 45 and 46 cm{sup −1}. These shifts are larger than those observed previously for HXeCl (27 and 16 cm{sup −1}) and HXeBr (37 and 23 cm{sup −1}); thus, the matrix effect is stronger for less stable molecules. The results for HXeI are qualitatively different from all previous results onmore » noble-gas hydrides with respect to the frequency order between Ar and Kr matrices. For previously studied HXeCl, HXeBr, and HXeCCH, the H–Xe stretching frequency is reliably (by >10 cm{sup −1}) higher in an Ar matrix than in a Kr matrix. In contrast, the H–Xe stretching frequency of HXeI in an Ar matrix is slightly lower than that in a Kr matrix. HXeH absorbs in Ar and Kr matrices at 1203.2 and 1192.1 cm{sup −1} (the stronger band for a Kr matrix), respectively. These bands are blue-shifted from the stronger band of HXeH in a Xe matrix (1166 cm{sup −1}) by 37 and 26 cm{sup −1}, and this frequency order is the same as observed for HXeCl, HXeBr, and HXeCCH but different from HXeI. The present hybrid quantum-classical simulations successfully describe the main experimental findings. For HXeI in the 〈110〉 (double substitution) site, the order of the H–Xe stretching frequencies (ν(Xe) < ν(Ar) < ν(Kr)) is in accord with the experimental observations, and also the frequency shifts in Ar and Kr matrices from a Xe matrix are well predicted (30 and 34 cm{sup −1}). Both in the theory and experiment, the order of the H–Xe stretching frequencies differs from the case of HXeCl, which suggests the adequate theoretical description of the matrix effect. For HXeH in the 〈100〉 (single substitution) site, the order of the frequencies is ν(Xe) < ν(Kr) < ν(Ar), which also agrees with the experiments. The calculated frequency shifts for HXeH in Ar and Kr matrices with respect to a Xe matrix (36 and 23 cm{sup −1}) are in a good agreement with the experiments. The present calculations predict an increase of the H–Xe stretching frequencies in the noble-gas matrices with respect to vacuum.« less

Enhanced Antigen Retrieval of Amyloid β Immunohistochemistry

PubMed Central

Kai, Hideaki; Ogino, Koichi; Hatsuta, Hiroyuki; Murayama, Shigeo; Kitamoto, Tetsuyuki

2012-01-01

Senile plaques, extracellular deposits of amyloid β peptide (Aβ), are one of the pathological hallmarks of Alzheimer disease (AD). As the standard immunohistochemical detection method for Aβ deposits, anti-Aβ immunohistochemistry combined with antigen retrieval (AR) by formic acid (FA) has been generally used. Here, we present a more efficient AR for Aβ antigen. On brain sections of AD and its mouse model, a double combination of either autoclave heating in EDTA buffer or digestion with proteinase K plus FA treatment reinforced Aβ immunoreactivity. A further triple combination of digestion with proteinase K (P), autoclave heating in EDTA buffer (A), and FA treatment (F), when employed in this order, gave a more enhanced immunoreactivity. Our PAF method prominently visualized various forms of Aβ deposits in AD that have not been clearly detected previously and revealed numerous minute-sized plaques both in AD and the mouse model. Quantification of Aβ loads showed that the AR effect by the PAF method was 1.86-fold (in the aged human brain) and 4.64-fold (in the mouse brain) higher than that by the FA method. Thus, the PAF method could have the potential to be the most sensitive tool so far to study Aβ pathology in AD and its mouse model. PMID:22821668

Landfalling Atmospheric Rivers in California—Historical and Future Impacts

NASA Astrophysics Data System (ADS)

Dettinger, M. D.; Ralph, F. M.

2014-12-01

During the past decade, a wide range of insights about the character and causes of extreme orographic precipitation in California has emerged, based on our growing understanding of the presence, mechanisms and impacts of "atmospheric rivers" (ARs) in the extratropical atmosphere. When an AR reaches and encounters the Coastal Ranges and Sierra Nevada of California, the resulting orographically driven storms are key players in many important weather, hydrologic and ecological processes in the State, including floods and floodplain inundations, droughts, groundwater recharge, and surface-water resources (see table). The intensities, storm totals, geographical distributions and impacts of AR storms in California are determined by many factors, including among the most straightforward: The numbers of ARs making landfall each year The amounts of vapor being transported by the ARs The direction of vapor transport by the AR relative to perpendiculars to the mountain ranges (for maximum uplift) The duration of AR passage overhead of a given location The temperature of an AR as a determinant of snowline altitudes The stability of the atmosphere within which the AR is embedded The closeness of the air in the AR to saturation (how much uplift is needed to drive intense precipitation) ARs are present in weather forecast models as well as in the long-range climate models used to project future climate changes in response to increasing greenhouse-gas concentrations in the atmosphere. Research into the future of ARs over California was first reported in the literature in 2011 (based on IPCC AR4 climate models) and is being extended now (to IPCC AR5 models) to assess projected changes in the full range of factors listed above with the aim of predicting how climate change will affect these important storms and their impacts in coming decades.

Subterranean production of neutrons, 39Ar and 21Ne: Rates and uncertainties

NASA Astrophysics Data System (ADS)

Šrámek, Ondřej; Stevens, Lauren; McDonough, William F.; Mukhopadhyay, Sujoy; Peterson, R. J.

2017-01-01

Accurate understanding of the subsurface production rate of the radionuclide 39Ar is necessary for argon dating techniques and noble gas geochemistry of the shallow and the deep Earth, and is also of interest to the WIMP dark matter experimental particle physics community. Our new calculations of subsurface production of neutrons, 21Ne , and 39Ar take advantage of the state-of-the-art reliable tools of nuclear physics to obtain reaction cross sections and spectra (TALYS) and to evaluate neutron propagation in rock (MCNP6). We discuss our method and results in relation to previous studies and show the relative importance of various neutron, 21Ne , and 39Ar nucleogenic production channels. Uncertainty in nuclear reaction cross sections, which is the major contributor to overall calculation uncertainty, is estimated from variability in existing experimental and library data. Depending on selected rock composition, on the order of 107-1010 α particles are produced in one kilogram of rock per year (order of 1-103 kg-1 s-1); the number of produced neutrons is lower by ∼ 6 orders of magnitude, 21Ne production rate drops by an additional factor of 15-20, and another one order of magnitude or more is dropped in production of 39Ar. Our calculation yields a nucleogenic 21Ne /4He production ratio of (4.6 ± 0.6) ×10-8 in Continental Crust and (4.2 ± 0.5) ×10-8 in Oceanic Crust and Depleted Mantle. Calculated 39Ar production rates span a great range from 29 ± 9 atoms kg-rock-1 yr-1 in the K-Th-U-enriched Upper Continental Crust to (2.6 ± 0.8) × 10-4 atoms kg-rock-1 yr-1 in Depleted Upper Mantle. Nucleogenic 39Ar production exceeds the cosmogenic production below ∼700 m depth and thus, affects radiometric ages of groundwater. The 39Ar chronometer, which fills in a gap between 3H and 14C , is particularly important given the need to tap deep reservoirs of ancient drinking water.

Batch and column studies on biosorption of acid dyes on fresh water macro alga Azolla filiculoides.

PubMed

Padmesh, T V N; Vijayaraghavan, K; Sekaran, G; Velan, M

2005-10-17

The biosorption of Acid red 88 (AR88), Acid green 3 (AG3) and Acid orange 7 (AO7) by deactivated fresh water macro alga Azolla filiculoides was investigated in batch mode. Langmuir and Freundlich adsorption models were used for the mathematical description of the batch biosorption equilibrium data and model constants were evaluated. The adsorption capacity was pH dependent with a maximum value of 109.0 mg/g at pH 7 for AR88, 133.5 mg/g at pH 3 for AG3 and 109.6 mg/g at pH 3 for AO7, respectively, was obtained. The pseudo first and second order kinetic models were also applied to the experimental kinetic data and high correlation coefficients favor pseudo second order model for the present systems. The ability of A. filiculoides to biosorb AG3 in packed column was also investigated. The column experiments were conducted to study the effect of important design parameters such as initial dye concentration (50-100 mg/L), bed height (15-25 cm) and flow rate (5-15 mL/min) to the well-adsorbed dye. At optimum bed height (25 cm), flow rate (5 mL/min) and initial dye concentration (100 mg/L), A. filiculoides exhibited 28.1mg/g for AG3. The Bed Depth Service Time model and the Thomas model were used to analyze the experimental data and the model parameters were evaluated.

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

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.

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

NASA Technical Reports Server (NTRS)

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

2016-01-01

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

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

PubMed

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

2016-12-01

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

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

PubMed

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

2017-02-16

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

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

PubMed Central

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

2017-01-01

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

Measuring the Perceived Quality of an AR-Based Learning Application: A Multidimensional Model

ERIC Educational Resources Information Center

Pribeanu, Costin; Balog, Alexandru; Iordache, Dragos Daniel

2017-01-01

Augmented reality (AR) technologies could enhance learning in several ways. The quality of an AR-based educational platform is a combination of key features that manifests in usability, usefulness, and enjoyment for the learner. In this paper, we present a multidimensional model to measure the quality of an AR-based application as perceived by…

Characterizing Cretaceous Glaciation Events: K-Ar Ages of Southern Ocean Sediments

NASA Astrophysics Data System (ADS)

Wright, M. A.; Hemming, S. R.; Barbeau, D. L.; Torfstein, A.; Pierce, E. L.; Williams, T.; McManus, J. F.; Gombiner, J.

2012-12-01

Evidence from paleosols and carbonate weathering models suggest that the Late Cretaceous had a supergreenhouse climate due to atmospheric CO2 concentrations two to four times greater than modern levels, tropical sea surface temperatures exceeding 35°C, and high-latitude temperatures exceeding 20°C. Despite this warmth, the Late Cretaceous was apparently punctuated by large (>25 m) and rapid (<<1 million year) sea-level changes, as recorded by marginal marine stratigraphic architectures and pelagic stable isotope compositions. The magnitude and tempo of these changes suggest a glacio-eustatic control, presumably from the growth and decay of continental ice sheets on Antarctica. Because continental glaciation tends to increase the weathering of bedrock and production of sediment delivered to the oceans, circum-Antarctic marine sediment flux would be expected to increase during periods of glaciation. In order to identify a Late Cretaceous glaciation signal from such marine records, we must first constrain the compositional signal of continental detritus in marine sediments. Here we report the results of downcore K-Ar analysis of the terrigenous sediments of Quaternary Weddell Sea cores PS1170-1 and PS1388-3 in order to identify the compositional signature of continent-derived detritus deposited in the Weddell Sea during a known glacial period. Further, we use our K-Ar analyses of circum-Antarctic Quaternary sediment cores to pinpoint potential sediment source areas. Having constrained this glaciation signal, we also present preliminary K-Ar and Sm-Nd analysis of the Campanian-Maastrictian boundary event (69 Ma) at Ocean Drilling Project site 690C to assess the controversial hypothesis of Late Cretaceous glaciation of Antarctica.

Linear diffusion model dating of cinder cones in Central Anatolia, Turkey

NASA Astrophysics Data System (ADS)

O'Sadnick, L. G.; Reid, M. R.; Cline, M. L.; Cosca, M. A.; Kuscu, G.

2013-12-01

The progressive decrease in slope angle, cone height and cone height/width ratio over time provides the basis for geomorphic dating of cinder cones using linear diffusion models. Previous research using diffusion models to date cinder cones has focused on the cone height/width ratio as the basis for dating cones of unknown age [1,2]. Here we apply linear diffusion models to dating cinder cones. A suite of 16 cinder cones from the Hasandağ volcano area of the Neogene-Quaternary Central Anatolian Volcanic Zone, for which samples are available, were selected for morphologic dating analysis. New 40Ar/39Ar dates for five of these cones range from 62 × 4 to 517 × 9 ka. Linear diffusion models were used to model the erosional degradation of each cone. Diffusion coefficients (κ) for the 5 cinder cones with known ages were constrained by comparing various modeled slope profiles to the current slope profile. The resulting κ is 7.5×0.5 m2kyr-1. Using this κ value, eruption ages were modeled for the remaining 11 cinder cones and range from 53×3 to 455×30 ka. These ages are within the range of ages previously reported for cinder cones in the Hasandağ region. The linear diffusion model-derived ages are being compared to additional new 40Ar/39Ar dates in order to further assess the applicability of morphological dating to constrain the ages of cinder cones. The relatively well-constrained κ value we obtained by applying the linear diffusion model to cinder cones that range in age by nearly 500 ka suggests that this model can be used to date cinder cones. This κ value is higher than the well-established value of κ =3.9 for a cinder cone in a similar climate [3]. Therefore our work confirms the importance of determining appropriate κ values from nearby cones with known ages. References 1. C.A. Wood, J. Volcanol. Geotherm. Res. 8, 137 (1980) 2. D.M. Wood, M.F. Sheridan, J. Volcanol. Geotherm. Res. 83, 241 (1998) 3. J.D. Pelletier, M.L. Cline, Geology 35, 1067 (2007)

The role of hydrological initial conditions on Atmospheric River floods in the Russian River basin

NASA Astrophysics Data System (ADS)

Cao, Q.; Mehran, A.; Ralph, M.; Cannon, F.; Lettenmaier, D. P.

2017-12-01

A body of work over the last decade or so has demonstrated that most major floods along the U.S. West Coast are attributable to Atmospheric Rivers (ARs). Antecedent hydrological conditions play an important part in the natural links between precipitation and floods, and this is especially the case in the Pacific Coastal region where precipitation is strongly winter-dominant, and many potentially flood-inducing events occur relatively early in the wet season. The Russian River Basin has these characteristics, the result of which is mostly dry soils at the onset of the fall precipitation season. There is therefore a tradeoff in terms of flood potential between the strength of AR events, and the time history of previous precipitation that has begun to wet soils and raise local water tables. In order to examine flood responses associated with varying precursor hydrological conditions, we first constructed a data set of AR events that were coincident with Peaks Over Threshold (POT) extreme discharge events at selected USGS stream gauges throughout the Russian River basin. We investigated the role of antecedent soil moisture and water table conditions on historical AR flooding, initially using an exploratory data analysis approach. We then implemented the Distributed Hydrology-Soil-Vegetation Model (DHSVM) over the entire basin and conducted modeling experiments for each of the POT events under climatological and extreme antecedent conditions. We reconstructed climatological soil moisture by assimilating in situ observations into long-term soil moisture simulations from the UCLA Western U.S. Drought Monitoring System. We explore an envelope of frequency distributions of floods given a range of AR-related extreme precipitation and various initial hydrologic conditions, which eventually should have implications for flood management decision-making.

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.

Wind Tunnel Study on Flows over Various Two-dimensional Idealized Urban-liked Surfaces

NASA Astrophysics Data System (ADS)

Ho, Yat-Kiu; Liu, Chun-Ho

2013-04-01

Extensive human activities (e.g. increased traffic emissions) emit a wide range of pollutants resulting in poor urban area air quality. Unlike open, flat and homogenous rural terrain, urban surface is complicated by the presence of buildings, obstacles and narrow streets. The irregular urban surfaces thus form a random roughness that further modifies the near-surface flows and pollutant dispersion. In this study, a physical modelling approach is employed to commence a series of wind tunnel experiments to study the urban-area air pollution problems. The flow characteristics over different hypothetical urban roughness surfaces were studied in a wind tunnel in isothermal conditions. Preliminary experiments were conducted based on six types of idealized two-dimensional (2D) street canyon models with various building-height-to-street-width (aspect) ratios (ARs) 1, 1/2, 1/4, 1/8, 1/10 and 1/12. The main instrumentation is an in-house 90o X-hotwire anemometry. In each set of configuration, a sampling street canyon was selected near the end of the streamwise domain. Its roof level, i.e. the transverse between the mid points of the upstream and downstream buildings, was divided into eight segments. The measurements were then recorded on the mid-plane of the spannwise domain along the vertical profile (from building roof level to the ceiling of wind tunnel) of the eight segments. All the data acquisition processes were handled by the NI data acquisition modules, NI 9239 and CompactDAQ-9188 hardware. Velocity calculation was carried out in the post-processing stage on a digital computer. The two-component flow velocities and velocity fluctuations were calculated at each sampling points, therefore, for each model, a streamwise average of eight vertical profiles of mean velocity and velocity fluctuations was presented. A plot of air-exchange rate (ACH) against ARs was also presented in order to examine the ventilation performance of different tested models. Preliminary results show that the near-ground turbulence behaviour (2 to 5 times of the building height) is relatively sensitive to the changes in ARs. The wider the streets (decrease in AR), the higher the turbulence level was observed. A similar behaviour is observed on the ventilation performance in which the ACH was increased with decreasing AR. Interestingly, a peak ACH value was observed around AR = 1/10 and was slightly dropped thereafter at AR = 1/12. The observation is in line with our previous large-eddy simulation (LES) results. These findings indicate that variability of urban-like surfaces is important to the near-ground turbulent boundary layer structure. Additional measurements on the flows and dispersions over building surfaces will be undertaken on a variety of ARs and building height variations to elucidate the complex transport and pollutant dispersion mechanism in urban areas.

Prediction of UT1-UTC, LOD and AAM χ3 by combination of least-squares and multivariate stochastic methods

NASA Astrophysics Data System (ADS)

Niedzielski, Tomasz; Kosek, Wiesław

2008-02-01

This article presents the application of a multivariate prediction technique for predicting universal time (UT1-UTC), length of day (LOD) and the axial component of atmospheric angular momentum (AAM χ 3). The multivariate predictions of LOD and UT1-UTC are generated by means of the combination of (1) least-squares (LS) extrapolation of models for annual, semiannual, 18.6-year, 9.3-year oscillations and for the linear trend, and (2) multivariate autoregressive (MAR) stochastic prediction of LS residuals (LS + MAR). The MAR technique enables the use of the AAM χ 3 time-series as the explanatory variable for the computation of LOD or UT1-UTC predictions. In order to evaluate the performance of this approach, two other prediction schemes are also applied: (1) LS extrapolation, (2) combination of LS extrapolation and univariate autoregressive (AR) prediction of LS residuals (LS + AR). The multivariate predictions of AAM χ 3 data, however, are computed as a combination of the extrapolation of the LS model for annual and semiannual oscillations and the LS + MAR. The AAM χ 3 predictions are also compared with LS extrapolation and LS + AR prediction. It is shown that the predictions of LOD and UT1-UTC based on LS + MAR taking into account the axial component of AAM are more accurate than the predictions of LOD and UT1-UTC based on LS extrapolation or on LS + AR. In particular, the UT1-UTC predictions based on LS + MAR during El Niño/La Niña events exhibit considerably smaller prediction errors than those calculated by means of LS or LS + AR. The AAM χ 3 time-series is predicted using LS + MAR with higher accuracy than applying LS extrapolation itself in the case of medium-term predictions (up to 100 days in the future). However, the predictions of AAM χ 3 reveal the best accuracy for LS + AR.

A brief review of augmented reality science learning

NASA Astrophysics Data System (ADS)

Gopalan, Valarmathie; Bakar, Juliana Aida Abu; Zulkifli, Abdul Nasir

2017-10-01

This paper reviews several literatures concerning the theories and model that could be applied for science motivation for upper secondary school learners (16-17 years old) in order to make the learning experience more amazing and useful. The embedment of AR in science could bring an awe-inspiring transformation on learners' viewpoint towards the respective subject matters. Augmented Reality is able to present the real and virtual learning experience with the addition of multiple media without replacing the real environment. Due to the unique feature of AR, it attracts the mass attention of researchers to implement AR in science learning. This impressive technology offers learners with the ultimate visualization and provides an astonishing and transparent learning experience by bringing to light the unseen perspective of the learning content. This paper will attract the attention of researchers in the related field as well as academicians in the related discipline. This paper aims to propose several related theoretical guidance that could be applied in science motivation to transform the learning in an effective way.

CG2AA: backmapping protein coarse-grained structures.

PubMed

Lombardi, Leandro E; Martí, Marcelo A; Capece, Luciana

2016-04-15

Coarse grain (CG) models allow long-scale simulations with a much lower computational cost than that of all-atom simulations. However, the absence of atomistic detail impedes the analysis of specific atomic interactions that are determinant in most interesting biomolecular processes. In order to study these phenomena, it is necessary to reconstruct the atomistic structure from the CG representation. This structure can be analyzed by itself or be used as an onset for atomistic molecular dynamics simulations. In this work, we present a computer program that accurately reconstructs the atomistic structure from a CG model for proteins, using a simple geometrical algorithm. The software is free and available online at http://www.ic.fcen.uba.ar/cg2aa/cg2aa.py Supplementary data are available at Bioinformatics online. lula@qi.fcen.uba.ar. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Androgen Receptor (AR) Physiological Roles in Male and Female Reproductive Systems: Lessons Learned from AR-Knockout Mice Lacking AR in Selective Cells1

PubMed Central

Chang, Chawnshang; Lee, Soo Ok; Wang, Ruey-Sheng; Yeh, Shuyuan; Chang, Ta-Min

2013-01-01

ABSTRACT Androgens/androgen receptor (AR) signaling is involved primarily in the development of male-specific phenotypes during embryogenesis, spermatogenesis, sexual behavior, and fertility during adult life. However, this signaling has also been shown to play an important role in development of female reproductive organs and their functions, such as ovarian folliculogenesis, embryonic implantation, and uterine and breast development. The establishment of the testicular feminization (Tfm) mouse model exploiting the X-linked Tfm mutation in mice has been a good in vivo tool for studying the human complete androgen insensitivity syndrome, but this mouse may not be the perfect in vivo model. Mouse models with various cell-specific AR knockout (ARKO) might allow us to study AR roles in individual types of cells in these male and female reproductive systems, although discrepancies are found in results between labs, probably due to using various Cre mice and/or knocking out AR in different AR domains. Nevertheless, no doubt exists that the continuous development of these ARKO mouse models and careful studies will provide information useful for understanding AR roles in reproductive systems of humans and may help us to develop more effective and more specific therapeutic approaches for reproductive system-related diseases. PMID:23782840

Measurement of the J = 0-1 rotational transitions of three isotopes of ArD(+)

NASA Technical Reports Server (NTRS)

Bowman, W. C.; Plummer, G. M.; Herbst, E.; De Lucia, F. C.

1983-01-01

The rotational transitions of all three isotopic species of ArD(+) in samples containing the Ar isotopes in their natural abundances have been measured by means of millimeter and submillimeter techniques that employ a magnetically enhanced abnormal glow discharge. All three transition frequency measurements were made from digitally averaged signals detected through a lock-in amplifier with a 10-msec time constant. The Ar-4OD(+) transition was easily visible in real time on an oscilloscope with SNR of about 15. It is noted that the observed transition of Ar-38D(+) is more than five orders of magnitude weaker than that due to HCO(+).

Photospheric Current Spikes and Their Possible Association with Flares - Results from an HMI Data Driven Model

NASA Technical Reports Server (NTRS)

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

2016-01-01

A data driven, near photospheric magnetohydrodynamic model predicts spikes in the horizontal current density, and associated resistive heating rate per unit volume Q. The spikes appear as increases by orders of magnitude above background values in neutral line regions (NLRs) of active regions (ARs). The largest spikes typically occur a few hours to a few days prior to M or X flares. The spikes correspond to large vertical derivatives of the horizontal magnetic field. The model takes as input the photospheric magnetic field observed by the Helioseismic & Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. This 2.5 D field is used to determine an analytic expression for a 3 D magnetic field, from which the current density, vector potential, and electric field are computed in every AR pixel for 14 ARs. The field is not assumed to be force-free. The spurious 6, 12, and 24 hour Doppler periods due to SDO orbital motion are filtered out of the time series of the HMI magnetic field for each pixel using a band pass filter. The subset of spikes analyzed at the pixel level are found to occur on HMI and granulation scales of 1 arcsec and 12 minutes. Spikes are found in ARs with and without M or X flares, and outside as well as inside NLRs, but the largest spikes are localized in the NLRs of ARs with M or X flares. The energy to drive the heating associated with the largest current spikes comes from bulk flow kinetic energy, not the electromagnetic field, and the current density is highly non-force free. The results suggest that, in combination with the model, HMI is revealing strong, convection driven, non-force free heating events on granulation scales, and that it is plausible these events are correlated with subsequent M or X flares. More and longer time series need to be analyzed to determine if such a correlation exists. Above an AR dependent threshold value of Q, the number of events N(Q) with heating rates greater than or equal to Q obeys a scale invariant power law distribution for each AR given by N(Q) varies Q(sup -s), where 0.40 less than or equal to S less than or equal to 0.53, with a mean and standard deviation across the 14 ARs of 0.47 and 0.045, showing there is little variation of S from one AR to another. These properties of N(Q) are in close agreement with those of the distribution N(E) for the total energy E of solar flares, determined from observations to be N(E) = constant x E(sup -alpha). From observations of nanoflares in the 0.7 to 4 MK range, and from observations of flares in hard X-rays, it is found that 0.51 less than or equal to alpha less than or equal to 0.57, and 0.4 less than or equal to alpha less than or equal to 0.6, respectively (Crosby et al. 1993, Sol. Phys., 143, 275; Aschwanden & Parnell 2002, ApJ, 572, 1048). Observations also show that, as is found here for the exponent S, there is little variation of alpha with AR (Wheatland 2000, ApJ, 532, 1209), indicating N(E) and N(Q) are largely independent of individual properties of ARs such as area, total magnetic flux, and distribution of current density (i.e. non-potentiality). Therefore the power law scaling of the photospheric heating rate Q computed here on granulation scales is essentially identical to that found for coronal observations of flare energies on scales 1-2 orders of magnitude larger. This suggests the physical mechanisms that cause Q and coronal flares are closely related. It seems likely that Q is the signature of a magnetic reconnection process in an energy range and volume orders of magnitude smaller than those of flares. In this context, at least the larger spikes in Q might be signatures of UV photospheric or lower chromospheric bombs in which plasma is heated to temperatures approximately 10(exp -5) K (Peter et al. 2014, Science 346, 1255726; Judge 2015, ApJ, 808, 116). In addition, lattice based avalanche simulations of flare energy release predict 0.4 less than or equal to alpha less than or equal to 0.5, while analytic, fractal-diffusive self-organized criticality models predict 0.4 less than or equal to alpha less than or equal to 0.67, in excellent agreement with observations, and the results presented here (Aschwanden & Parnell 2002, ApJ, 572, 1048; Aschwanden 2012, A&A, 539, A2; Aschwanden 2013, in "Self Organized Criticality Systems"; Aschwanden et al. 2016, SSR, 198, 47).

Salient Feature of Haptic-Based Guidance of People in Low Visibility Environments Using Hard Reins.

PubMed

Ranasinghe, Anuradha; Sornkarn, Nantachai; Dasgupta, Prokar; Althoefer, Kaspar; Penders, Jacques; Nanayakkara, Thrishantha

2016-02-01

This paper presents salient features of human-human interaction where one person with limited auditory and visual perception of the environment (a follower) is guided by an agent with full perceptual capabilities (a guider) via a hard rein along a given path. We investigate several salient features of the interaction between the guider and follower such as: 1) the order of an autoregressive (AR) control policy that maps states of the follower to actions of the guider; 2) how the guider may modulate the pulling force in response to the trust level of the follower; and 3) how learning may successively apportion the responsibility of control across different muscles of the guider. Based on experimental systems identification on human demonstrations from ten pairs of naive subjects, we show that guiders tend to adopt a third-order AR predictive control policy and followers tend to adopt second-order reactive control policy. Moreover, the extracted guider's control policy was implemented and validated by human-robot interaction experiments. By modeling the follower's dynamics with a time varying virtual damped inertial system, we found that it is the coefficient of virtual damping which is most sensitive to the trust level of the follower. We used these experimental insights to derive a novel controller that integrates an optimal order control policy with a push/pull force modulator in response to the trust level of the follower monitored using a time varying virtual damped inertial model.

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.

Are Public Master's Institutions Cost Efficient? A Stochastic Frontier and Spatial Analysis

ERIC Educational Resources Information Center

Titus, Marvin A.; Vamosiu, Adriana; McClure, Kevin R.

2017-01-01

The current study examines costs, measured by educational and general (E&G) spending, and cost efficiency at 252 public master's institutions in the United States over a nine-year (2004-2012) period. We use a multi-product quadratic cost function and results from a random-effects model with a first-order autoregressive (AR1) disturbance term…

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

Theoretical Investigation of Anharmonic Effects Observed in the Infrared Spectra of the Formaldehyde Cation and its Hydroxymethylene Isomer

NASA Astrophysics Data System (ADS)

Madison, Lindsey R.; Mosley, Jonathan; Mauney, Daniel; Duncan, Michael A.; McCoy, Anne B.

2016-06-01

Formaldehyde is the smallest organic molecule and is a prime candidate for a thorough investigation regarding the anharmonic approximations made in computationally modeling its infrared spectrum. Mass-selected ion spectroscopy was used to detect mass 30 cations which include of HCOH^+ and CH_2O^+. In order to elucidate the differences between the structures of these isomers, infrared spectroscopy was performed on the mass 30 cations using Ar predissociation. Interestingly, several additional spectral features are observed that cannot be explained by the fundamental OH and CH stretch vibrations alone. By including anharmonic coupling between OH and CH stretching and various overtones and combination bands involving lower frequency vibrations, we are able to identify how specific modes couple and lead to the experimentally observed spectral features. We combine straight-forward, ab initio calculations of the anharmonic frequencies of the mass 30 cations with higher order, adiabatic approximations and Fermi resonance models. By including anharmonic effects we are able to confirm that the isomers of the CH_2O^+\\cdotAr system have substantially different, and thus distinguishable, IR spectra and that many of the features can only be explained with anharmonic treatments.

Augmented reality for biomedical wellness sensor systems

NASA Astrophysics Data System (ADS)

Jenkins, Jeffrey; Szu, Harold

2013-05-01

Due to the commercial move and gaming industries, Augmented Reality (AR) technology has matured. By definition of AR, both artificial and real humans can be simultaneously present and realistically interact among one another. With the help of physics and physiology, we can build in the AR tool together with real human day-night webcam inputs through a simple interaction of heat transfer -getting hot, action and reaction -walking or falling, as well as the physiology -sweating due to activity. Knowing the person age, weight and 3D coordinates of joints in the body, we deduce the force, the torque, and the energy expenditure during real human movements and apply to an AR human model. We wish to support the physics-physiology AR version, PPAR, as a BMW surveillance tool for senior home alone (SHA). The functionality is to record senior walking and hand movements inside a home environment. Besides the fringe benefit of enabling more visits from grand children through AR video games, the PP-AR surveillance tool may serve as a means to screen patients in the home for potential falls at points around in house. Moreover, we anticipate PP-AR may help analyze the behavior history of SHA, e.g. enhancing the Smartphone SHA Ubiquitous Care Program, by discovering early symptoms of candidate Alzheimer-like midnight excursions, or Parkinson-like trembling motion for when performing challenging muscular joint movements. Using a set of coordinates corresponding to a set of 3D positions representing human joint locations, we compute the Kinetic Energy (KE) generated by each body segment over time. The Work is then calculated, and converted into calories. Using common graphics rendering pipelines, one could invoke AR technology to provide more information about patients to caretakers. Alerts to caretakers can be prompted by a patient's departure from their personal baseline, and the patient's time ordered joint information can be loaded to a graphics viewer allowing for high-definition digital reconstruction. Then an entire scene can be viewed from any position in virtual space, and AR can display certain measurements values which either constituted an alert, or otherwise indicate signs of the transition from wellness to illness.

In Vitro Mutational Analysis of the β2 Adrenergic Receptor, an In Vivo Surrogate Odorant Receptor

PubMed Central

Pfister, Patrick; Tomoiaga, Delia; Rogers, Matthew E.; Feinstein, Paul

2015-01-01

Many G-protein coupled receptors (GPCRs), such as odorant receptors (ORs), cannot be characterized in heterologous cells because of their difficulty in trafficking to the plasma membrane. In contrast, a surrogate OR, the GPCR mouse β2-adrenergic-receptor (mβ2AR), robustly traffics to the plasma membrane. We set out to characterize mβ2AR mutants in vitro for their eventual use in olfactory axon guidance studies. We performed an extensive mutational analysis of mβ2AR using a Green Fluorescent Protein-tagged mβ2AR (mβ2AR::GFP) to easily assess the extent of its plasma membrane localization. In order to characterize mutants for their ability to successfully transduce ligand-initiated signal cascades, we determined the half maximal effective concentrations (EC50) and maximal response to isoprenaline, a known mβ2AR agonist. Our analysis reveals that removal of amino terminal (Nt) N-glycosylation sites and the carboxy terminal (Ct) palmitoylation site of mβ2AR do not affect its plasma membrane localization. By contrast, when both the Nt and Ct of mβ2AR are replaced with those of M71 OR, plasma membrane trafficking is impaired. We further analyze three mβ2AR mutants (RDY, E268A, and C327R) used in olfactory axon guidance studies and are able to decorrelate their plasma membrane trafficking with their capacity to respond to isoprenaline. A deletion of the Ct prevents proper trafficking and abolishes activity, but plasma membrane trafficking can be selectively rescued by a Tyrosine to Alanine mutation in the highly conserved GPCR motif NPxxY. This new loss-of-function mutant argues for a model in which residues located at the end of transmembrane domain 7 can act as a retention signal when unmasked. Additionally, to our surprise, amongst our set of mutations only Ct mutations appear to lower mβ2AR EC50s revealing their critical role in G-protein coupling. We propose that an interaction between the Nt and Ct is necessary for proper folding and/or transport of GPCRs. PMID:26513247

Anomalous behavior in temporal evolution of ripple wavelength under medium energy Ar{sup +}-ion bombardment on Si: A case of initial wavelength selection

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

Garg, Sandeep Kumar; Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110 067; Cuerno, Rodolfo

We have studied the early stage dynamics of ripple patterns on Si surfaces, in the fluence range of 1–3 × 10{sup 18} ions cm{sup −2}, as induced by medium energy Ar{sup +}-ion irradiation at room temperature. Under our experimental conditions, the ripple evolution is found to be in the linear regime, while a clear decreasing trend in the ripple wavelength is observed up to a certain time (fluence). Numerical simulations of a continuum model of ion-sputtered surfaces suggest that this anomalous behavior is due to the relaxation of the surface features of the experimental pristine surface during the initial stage of patternmore » formation. The observation of this hitherto unobserved behavior of the ripple wavelength seems to have been enabled by the use of medium energy ions, where the ripple wavelengths are found to be order(s) of magnitude larger than those at lower ion energies.« less

Intraocular Pressure, Blood Pressure, and Retinal Blood Flow Autoregulation: A Mathematical Model to Clarify Their Relationship and Clinical Relevance

PubMed Central

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-01-01

Purpose. This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. Methods. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. Results. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. Conclusions. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. PMID:24876284

Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance.

PubMed

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-05-29

This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Auger recombination in Dirac materials: A tangle of many-body effects

NASA Astrophysics Data System (ADS)

Alymov, Georgy; Vyurkov, Vladimir; Ryzhii, Victor; Satou, Akira; Svintsov, Dmitry

2018-05-01

The peculiar electron dispersion in Dirac materials makes lowest-order Auger processes prohibited or marginally prohibited by energy and momentum conservation laws. Thus, Auger recombination (AR) in these materials is very sensitive to many-body effects. We incorporate them at the level of the G W approximation into the nonequilibrium Green's functions approach to AR and study the role of dynamic screening, spectrum broadening, and renormalization in the case of weakly pumped undoped graphene. We find that incorrect treatment of many-body effects can lead to an order-of-magnitude error in the recombination rate. We show that the AR time depends weakly (sublinearly) on the background dielectric constant, which limits the possibility to control recombination by the choice of substrate. However, the AR time can be considerably prolonged by placing graphene under a metal gate or by introducing a band gap. With carrier cooling taken into account, our results comply with experiments on photoexcited graphene.

Augmented reality in a tumor resection model.

PubMed

Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

2018-03-01

Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

Analyzing Enterprise Networks Needs: Action Research from the Mechatronics Sector

NASA Astrophysics Data System (ADS)

Cagnazzo, Luca; Taticchi, Paolo; Bidini, Gianni; Baglieri, Enzo

New business models and theories are developing nowadays towards collaborative environments direction, and many new tools in sustaining companies involved in these organizations are emerging. Among them, a plethora of methodologies to analyze their needs are already developed for single companies. Few academic works are available about Enterprise Networks (ENs) need analysis. This paper presents the learning from an action research (AR) in the mechatronics sector: AR has been used in order to experience the issue of evaluating network needs and therefore define, develop, and test a complete framework for network evaluation. Reflection on the story in the light of the experience and the theory is presented, as well as extrapolation to a broader context and articulation of usable knowledge.

Ar 3p photoelectron sideband spectra in two-color XUV + NIR laser fields

NASA Astrophysics Data System (ADS)

Minemoto, Shinichirou; Shimada, Hiroyuki; Komatsu, Kazma; Komatsubara, Wataru; Majima, Takuya; Mizuno, Tomoya; Owada, Shigeki; Sakai, Hirofumi; Togashi, Tadashi; Yoshida, Shintaro; Yabashi, Makina; Yagishita, Akira

2018-04-01

We performed photoelectron spectroscopy using femtosecond XUV pulses from a free-electron laser and femtosecond near-infrared pulses from a synchronized laser, and succeeded in measuring Ar 3p photoelectron sideband spectra due to the two-color above-threshold ionization. In our calculations of the first-order time-dependent perturbation theoretical model based on the strong field approximation, the photoelectron sideband spectra and their angular distributions are well reproduced by considering the timing jitter between the XUV and the NIR pulses, showing that the timing jitter in our experiments was distributed over the width of {1.0}+0.4-0.2 ps. The present approach can be used as a method to evaluate the timing jitter inevitable in FEL experiments.

Models for Serially Correlated Over or Underdispersed Unequally Spaced Longitudinal Count Data with Applications to Asthma Inhaler Use

DTIC Science & Technology

2007-08-01

the gamma prior and Poisson counts are conditioned on an unobserved AR( 1 ) process that accounts for the time since the last observation . This model did...to the observation equation. For unequally spaced observations the AR( 1 ) errors are replaced by a continuous time AR( 1 ) process , and the distance...unequal spaced observations are handled in the XJG model by assuming an underlying continuous time AR( 1 ) (CAR(l)) process . It is implemented by

The expression of β3-adrenoceptors and their function in the human prostate.

PubMed

Suzuki, Takahisa; Otsuka, Atsushi; Matsumoto, Rikiya; Furuse, Hiroshi; Ozono, Seiichiro

2016-02-01

Little is known about β3-adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of β-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective β-AR subtype agonist was most involved in the relaxation of isolated human prostate strips. Messenger RNA (mRNA) expression for β1-, β2-, and β3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of β-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions. We confirmed the presence of mRNA for β1-, β2-, and β3-ARs both in normal prostate and in BPH tissues. For β3-AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in β1- and β2-AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different β-AR subtypes. Staining of β3-AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective β-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective β-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions. β3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by β1- and β3-AR stimulation. β3-AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction. © 2015 Wiley Periodicals, Inc.

Re-evaluation of polyphase kinematic and 40Ar/39Ar cooling history of Moldanubian hot nappe at the eastern margin of the Bohemian Massif

NASA Astrophysics Data System (ADS)

Racek, M.; Lexa, O.; Schulmann, K.; Corsini, M.; Štípská, P.; Maierová, P.

2017-03-01

A structural and geochronological 40Ar/39Ar study was performed in kilometre-scale middle and lower crustal lens-shaped domains dominated by a preserved subvertical foliation, surrounded by horizontally foliated migmatites. These domains occur within the Moldanubian nappe overlying the Brunia microcontinent at the eastern margin of the European Variscides. Three main deformation phases were recognized: subvertical S2 fabric trending NW-SE in lower crustal rocks and NE-SW in mid-crustal rocks. It is reworked by HT/MT horizontal fabric S3 along margins of crustal domains and in surrounding migmatites. S3 bears a prolate NE lineation parallel to the S2-S3 intersection in the lower crustal domain. In the middle crustal units, L3 is weak, connected to oblate strain and trends NE-SW parallel to the S2-S3 intersection. D4 non-coaxial shear deformation is mainly localized at the boundary between the Moldanubian nappe and Brunia and bears strong top to the NNE shear criteria. In order to constrain kinematics of the D3 deformation, strain modelling was performed to show that the Moldanubian hot nappe was frontally thrust over the Brunia indentor. The renewed D4 tangential movement only heterogeneously reactivates the horizontal S3. This evolution is recorded in 40Ar/39Ar amphibole cooling ages, which show two statistically significant Carboniferous peaks at 342 and 332 Ma, which are also reflected by published detrital muscovite 40Ar/39Ar ages in the adjacent foreland basin. This geochronological record is correlated with progressive erosion of the topographically elevated upper crustal part of the Moldanubian nappe during D3 frontal thrusting, followed by greenschist facies D4 transpressive reactivation and subsequent erosion of high-grade parts of the nappe.

A collisional-radiative model for low-pressure weakly magnetized Ar plasmas

NASA Astrophysics Data System (ADS)

Zhu, Xi-Ming; Tsankov, Tsanko; Czarnetzki, Uwe; Marchuk, Oleksandr

2016-09-01

Collisional-radiative (CR) models are widely investigated in plasma physics for describing the kinetics of reactive species and for optical emission spectroscopy. This work reports a new Ar CR model used in low-pressure (0.01-10 Pa) weakly magnetized (<0.1 Tesla) plasmas, including ECR, helicon, and NLD discharges. In this model 108 realistic levels are individually studied, i.e. 51 lowest levels of the Ar atom and 57 lowest levels of the Ar ion. We abandon the concept of an ``effective level'' usually adopted in previous models for glow discharges. Only in this way the model can correctly predict the non-equilibrium population distribution of close energy levels. In addition to studying atomic metastable and radiative levels, this model describes the kinetic processes of ionic metastable and radiative levels in detail for the first time. This is important for investigation of plasma-surface interaction and for optical diagnostics using atomic and ionic line-ratios. This model could also be used for studying Ar impurities in tokamaks and astrophysical plasmas.

Detection of tripping gait patterns in the elderly using autoregressive features and support vector machines.

PubMed

Lai, Daniel T H; Begg, Rezaul K; Taylor, Simon; Palaniswami, Marimuthu

2008-01-01

Elderly tripping falls cost billions annually in medical funds and result in high mortality rates often perpetrated by pulmonary embolism (internal bleeding) and infected fractures that do not heal well. In this paper, we propose an intelligent gait detection system (AR-SVM) for screening elderly individuals at risk of suffering tripping falls. The motivation of this system is to provide early detection of elderly gait reminiscent of tripping characteristics so that preventive measures could be administered. Our system is composed of two stages, a predictor model estimated by an autoregressive (AR) process and a support vector machine (SVM) classifier. The system input is a digital signal constructed from consecutive measurements of minimum toe clearance (MTC) representative of steady-state walking. The AR-SVM system was tested on 23 individuals (13 healthy and 10 having suffered at least one tripping fall in the past year) who each completed a minimum of 10 min of walking on a treadmill at a self-selected pace. In the first stage, a fourth order AR model required at least 64 MTC values to correctly detect all fallers and non-fallers. Detection was further improved to less than 1 min of walking when the model coefficients were used as input features to the SVM classifier. The system achieved a detection accuracy of 95.65% with the leave one out method using only 16 MTC samples, but was reduced to 69.57% when eight MTC samples were used. These results demonstrate a fast and efficient system requiring a small number of strides and only MTC measurements for accurate detection of tripping gait characteristics.

Mantle rare gas relative abundances in a steady-state mass transport model

NASA Technical Reports Server (NTRS)

Porcelli, D.; Wasserburg, G. J.

1994-01-01

A model for He and Xe was presented previously which incorporates mass transfer of rare gases from an undegassed lower mantle (P) and the atmosphere into a degassed upper mantle (D). We extend the model to include Ne and Ar. Model constraints on rare gas relative abundances within P are derived. Discussions of terrestrial volatile acquisition have focused on the rare gas abundance pattern of the atmosphere relative to meteoritic components, and the pattern of rare gases still trapped in the Ear,th is important in identifying volatile capture and loss processes operating during Earth formation. The assumptions and principles of the model are discussed in Wasserburg and Porcelli (this volume). For P, the concentrations in P of the decay/nuclear products 4 He, 21 Ne, 40 Ar, and 136 Xe can be calculated from the concentrations of the parent elements U, Th, K, and Pu. The total concentration of the daughter element in P is proportional to the isotopic shifts in P. For Ar, ((40)Ar/(36)Ar)p - ((40)Ar/(36)Ar)o =Delta (exp 40) p= 40 Cp/(exp 36)C where(i)C(sub j) the concentration of isotope i in j. In D, isotope compositions are the result of mixing rare gases from P, decay/nuclear products generated in the upper mantle, and subducted rare gases (for Ar and Xe).

Analytical Modeling of Weld Bead Shape in Dry Hyperbaric GMAW Using Ar-He Chamber Gas Mixtures

NASA Astrophysics Data System (ADS)

Azar, Amin S.; Ås, Sigmund K.; Akselsen, Odd M.

2013-03-01

Hyperbaric arc welding is a special application of joining the pipeline steels under seawater. In order to analyze the behavior of the arc under ambient pressure, a model is required to estimate the arc efficiency. A distributed point heat source model was employed. The simulated isotherms were calibrated iteratively to fit the actual bead cross section. Basic gas mixture rules and models were used to calculate the thermal properties of the low-temperature shielding gas under the ambient pressure of 10 bar. Nine bead-on-plate welds were deposited each of which under different Ar-He chamber gas compositions. The well-known correlation between arc efficiency (delivered heat) and the thermal conductivity was established for different gas mixtures. The arc efficiency was considered separately for the transverse and perpendicular heat sources. It was found that assigning single heat efficiency factor for the entire arc, which is usually below unity, causes a noticeable underestimation for the heat transfer in the perpendicular direction and a little overestimation in the transverse direction.

Structured Antireflective Coating for Silicon at Submillimeter Frequencies

NASA Astrophysics Data System (ADS)

Padilla, Estefania

2018-01-01

Observations at millimeter and submillimeter wavelengths are useful for many astronomical studies, such as the polarization of the cosmic microwave background or the formation and evolution of galaxy clusters. In order to allow observations over a broad spectral bandwidth (approximatively from 70 to 420 GHz), innovative broadband anti-reflective (AR) optics must be utilized in submillimeter telescopes. Due to its low loss and high refractive index, silicon is a fine optical material at these frequencies, but an AR coating with multiple layers is required to maximize its transmission over a wide bandwidth. Structured multilayer AR coatings for silicon are currently being developed at Caltech and JPL. The development process includes the design of the structured layers with commercial electromagnetic simulation software, the fabrication by using deep reactive ion etching, and the test of the transmission and reflection of the patterned wafers. Geometrical 3D patterns have successfully been etched at the surface of the silicon wafers creating up to 2 layers with different effective refractive indices. The transmission and reflection of single AR layer wafers, measured between 75 and 330 GHz, are close to the simulation predictions. These results allow the development of new designs with 5 or 6 AR layers in order to improve the bandwidth and transmission of the silicon AR coatings.

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).

Nonlinear time series modeling and forecasting the seismic data of the Hindu Kush region

NASA Astrophysics Data System (ADS)

Khan, Muhammad Yousaf; Mittnik, Stefan

2018-01-01

In this study, we extended the application of linear and nonlinear time models in the field of earthquake seismology and examined the out-of-sample forecast accuracy of linear Autoregressive (AR), Autoregressive Conditional Duration (ACD), Self-Exciting Threshold Autoregressive (SETAR), Threshold Autoregressive (TAR), Logistic Smooth Transition Autoregressive (LSTAR), Additive Autoregressive (AAR), and Artificial Neural Network (ANN) models for seismic data of the Hindu Kush region. We also extended the previous studies by using Vector Autoregressive (VAR) and Threshold Vector Autoregressive (TVAR) models and compared their forecasting accuracy with linear AR model. Unlike previous studies that typically consider the threshold model specifications by using internal threshold variable, we specified these models with external transition variables and compared their out-of-sample forecasting performance with the linear benchmark AR model. The modeling results show that time series models used in the present study are capable of capturing the dynamic structure present in the seismic data. The point forecast results indicate that the AR model generally outperforms the nonlinear models. However, in some cases, threshold models with external threshold variables specification produce more accurate forecasts, indicating that specification of threshold time series models is of crucial importance. For raw seismic data, the ACD model does not show an improved out-of-sample forecasting performance over the linear AR model. The results indicate that the AR model is the best forecasting device to model and forecast the raw seismic data of the Hindu Kush region.

OEDGE modeling of plasma contamination efficiency of Ar puffing from different divertor locations in EAST

NASA Astrophysics Data System (ADS)

Pengfei, ZHANG; Ling, ZHANG; Zhenwei, WU; Zong, XU; Wei, GAO; Liang, WANG; Qingquan, YANG; Jichan, XU; Jianbin, LIU; Hao, QU; Yong, LIU; Juan, HUANG; Chengrui, WU; Yumei, HOU; Zhao, JIN; J, D. ELDER; Houyang, GUO

2018-04-01

Modeling with OEDGE was carried out to assess the initial and long-term plasma contamination efficiency of Ar puffing from different divertor locations, i.e. the inner divertor, the outer divertor and the dome, in the EAST superconducting tokamak for typical ohmic plasma conditions. It was found that the initial Ar contamination efficiency is dependent on the local plasma conditions at the different gas puff locations. However, it quickly approaches a similar steady state value for Ar recycling efficiency >0.9. OEDGE modeling shows that the final equilibrium Ar contamination efficiency is significantly lower for the more closed lower divertor than that for the upper divertor.

Non-parametric directionality analysis - Extension for removal of a single common predictor and application to time series.

PubMed

Halliday, David M; Senik, Mohd Harizal; Stevenson, Carl W; Mason, Rob

2016-08-01

The ability to infer network structure from multivariate neuronal signals is central to computational neuroscience. Directed network analyses typically use parametric approaches based on auto-regressive (AR) models, where networks are constructed from estimates of AR model parameters. However, the validity of using low order AR models for neurophysiological signals has been questioned. A recent article introduced a non-parametric approach to estimate directionality in bivariate data, non-parametric approaches are free from concerns over model validity. We extend the non-parametric framework to include measures of directed conditional independence, using scalar measures that decompose the overall partial correlation coefficient summatively by direction, and a set of functions that decompose the partial coherence summatively by direction. A time domain partial correlation function allows both time and frequency views of the data to be constructed. The conditional independence estimates are conditioned on a single predictor. The framework is applied to simulated cortical neuron networks and mixtures of Gaussian time series data with known interactions. It is applied to experimental data consisting of local field potential recordings from bilateral hippocampus in anaesthetised rats. The framework offers a non-parametric approach to estimation of directed interactions in multivariate neuronal recordings, and increased flexibility in dealing with both spike train and time series data. The framework offers a novel alternative non-parametric approach to estimate directed interactions in multivariate neuronal recordings, and is applicable to spike train and time series data. Copyright © 2016 Elsevier B.V. All rights reserved.

Endoglucanase and xylanase production by Bacillus sp. AR03 in co-culture.

PubMed

Hero, Johan S; Pisa, José H; Perotti, Nora I; Romero, Cintia M; Martínez, María A

2017-07-03

The behavior of three isolates retrieved from different cellulolytic consortia, Bacillus sp. AR03, Paenibacillus sp. AR247 and Achromobacter sp. AR476-2, were examined individually and as co-cultures in order to evaluate their ability to produce extracellular cellulases and xylanases. Utilizing a peptone-based medium supplemented with carboxymethyl cellulose (CMC), an increase estimation of 1.30 and 1.50 times was obtained by the co-culture containing the strains AR03 and AR247, with respect to enzyme titles registered by their individual cultivation. On the contrary, the extracellular enzymatic production decreased during the co-cultivation of strain AR03 with the non-cellulolytic Achromobacter sp. AR476-2. The synergistic behavior observed through the combined cultivation of the strains AR03 and AR247 might be a consequence of the consumption by Paenibacillus sp. AR247 of the products of the CMC hydrolysis (i.e., cellobiose and/or cello-oligosaccharides), which were mostly generated by the cellulase producer Bacillus sp. AR03. The effect observed could be driven by the requirement to fulfill the nutritional supply from both strains on the substrate evaluated. These results would contribute to a better description of the degradation of the cellulose fraction of the plant cell walls in nature, expected to an efficient utilization of renewable sources.

Effects of elliptical burner geometry on partially premixed gas jet flames in quiescent surroundings

NASA Astrophysics Data System (ADS)

Baird, Benjamin

This study is the investigation of the effect of elliptical nozzle burner geometry and partial premixing, both 'passive control' methods, on a hydrogen/hydrocarbon flame. Both laminar and turbulent flames for circular, 3:1, and 4:1 aspect ratio (AR) elliptical burners are considered. The amount of air mixed with the fuel is varied from fuel-lean premixed flames to fuel-rich partially premixed flames. The work includes measurements of flame stability, global pollutant emissions, flame radiation, and flame structure for the differing burner types and fuel conditions. Special emphasis is placed on the near-burner region. Experimentally, both conventional (IR absorption, chemiluminecent, and polarographic emission analysis,) and advanced (laser induced fluorescence, planar laser induced fluorescence, Laser Doppler Velocimetry (LDV), Rayleigh scattering) diagnostic techniques are used. Numerically, simulations of 3-dimensional laminar and turbulent reacting flow are conducted. These simulations are run with reduced chemical kinetics and with a Reynolds Stress Model (RSM) for the turbulence modeling. It was found that the laminar flames were similar in appearance and overall flame length for the 3:1 AR elliptical and the circular burner. The laminar 4:1 AR elliptical burner flame split into two sub-flames along the burner major axis. This splitting had the effect of greatly shortening the 4:1 AR elliptical burner flame to have an overall flame length about half of that of the circular and 3:1 AR elliptical burner flames. The length of all three burners flames increased with increasing burner exit equivalence ratio. The blowout velocity for the three burners increased with increase in hydrogen mass fraction of the hydrogen/propane fuel mixture. For the rich premixed flames, the circular burner was the most stable, the 3:1 AR elliptical burner, was the least stable, and the 4:1 AR elliptical burner was intermediate to the two other burners. This order of stability was due to two reasons. The elliptical burners have enhanced turbulence generation that lowers their stability when compared to the circular burner. The 4:1 AR elliptical burner had greater stability due to a greater velocity decay rate and wider OH reaction zones particularly in the region between the two jets. The 3:1 AR elliptical and circular burners produced similar carbon monoxide and nitric oxide emission indexes over the range of equivalence ratios of 0.55 to 4.0, for laminar flames. (Abstract shortened by UMI.)

Immunohistochemical localization of alpha and beta adrenergic receptors in the human nasal turbinate.

PubMed

Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

2016-06-01

Adrenergic receptors (ARs) include four general types (α1, α2, β1 and β2), which are found in different target tissues. α-AR agonists are commonly used for decongestant therapy of upper airway diseases. In order to clarify the roles of AR subtypes in the upper airways, we investigated the localization of these receptors by immunohistochemistry. Human turbinates were obtained after turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The specific cells expressing α- and β-AR proteins were identified by immunostaining using an anti-human AR subtype-specific antibodies (α1A-, α1D-, α2C- and β2-ARs) antibody. Immunohistochemical analysis revealed that immunoreactivities for α1D- and β2-ARs were densely distributed in submucosal glands. In contrast, immunoreactivities for α1A- and 2C-ARs were densely distributed in vascular smooth muscle. Our results suggested that adrenergic receptor (AR) subtypes had different roles in upper airway diseases, such as allergic rhinitis and nonallergic rhinitis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2018-03-23

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

Characterization of karyopherins in androgen receptor intracellular trafficking in the yeast model

PubMed Central

Nguyen, Minh M; Harmon, Robert M; Wang, Zhou

2014-01-01

Background: Mechanisms regulating androgen receptor (AR) subcellular localization represent an essential component of AR signaling. Karyopherins are a family of nucleocytoplasmic trafficking factors. In this paper, we used the yeast model to study the effects of karyopherins on the subcellular localization of the AR. Methods: Yeast mutants deficient in different nuclear transport factors were transformed with various AR based, GFP tagged constructs and their localization was monitored using microscopy. Results: We showed that yeast can mediate androgen-induced AR nuclear localization and that in addition to the import factor, Importinα/β, this process required the import karyopherin Sxm1. We also showed that a previously identified nuclear export sequence (NESAR) in the ligand binding domain of AR does not appear to rely on karyopherins for cytoplasmic localization. Conclusions: These results suggest that while AR nuclear import relies on karyopherin activity, AR nuclear export and/or cytoplasmic localization may require other undefined mechanisms. PMID:25031696

Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

PubMed

Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K; Dehaen, Wim; de Witte, Peter A M; Esguerra, Camila V

2013-01-01

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

Insights from Zebrafish and Mouse Models on the Activity and Safety of Ar-Turmerone as a Potential Drug Candidate for the Treatment of Epilepsy

PubMed Central

Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K.; Dehaen, Wim; de Witte, Peter A. M.; Esguerra, Camila V.

2013-01-01

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application. PMID:24349101

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.

Order-of-magnitude differences in retention of low-energy Ar implanted in Si and SiO{sub 2}

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

Wittmaack, Klaus, E-mail: wittmaack@helmholtz-muenchen.de; Giordani, Andrew; Umbel, Rachel

The retention of 1 and 5 keV Ar implanted at 45° in Si and 4.3 nm SiO{sub 2} on Si was studied at fluences between 3 × 10{sup 14} and 1.5 × 10{sup 16} cm{sup −2}. X-ray photoelectron spectroscopy (XPS) served to monitor the accumulation of Ar as well as the removal of SiO{sub 2}. Bombardment induced changes in oxygen chemistry caused the O 1s peak position to move toward lower binding energies by as much as 2.2 eV. Plotted versus depth of erosion, the fluence dependent changes in oxygen content, and peak position were similar at 1 and 5 keV. The Ar content of Si increased with increasingmore » exposure, saturating at fluences of ∼2 × 10{sup 15} cm{sup −2} (1 keV) and ∼6 × 10{sup 15} cm{sup −2} (5 keV). Much less Ar was retained in the SiO{sub 2}/Si sample, notably at 1 keV, in which case the low-fluence Ar signal amounted to only 8% of the Si reference. The results imply that essentially no Ar was trapped in undamaged SiO{sub 2}, i.e., the Ar atoms initially observed by XPS were located underneath the oxide. At the lowest fluence of 5 keV Ar, the retention ratio was much higher (43%) because the oxide was already highly damaged, with an associated loss of oxygen. The interpretation was assisted by TRIM(SRIM) calculations of damage production. Partial maloperation of the ion beam raster unit, identified only at a late stage of this work, enforced a study on the uniformity of bombardment. The desired information could be obtained by determining x,y line scan profiles of O 1s across partially eroded SiO{sub 2}/Si samples. Fluence dependent Ar retention in Si was described using an extended version of the rapid relocation model which takes into account that insoluble implanted rare-gas atoms tend to migrate to the surface readily under ongoing bombardment. The range parameters required for the modeling were determined using TRIM(SRIM); sputtering yields were derived from the literature. The other three parameters determining the Ar signal, i.e., (1) the thickness w of the near-surface Si region devoid of Ar, (2) the relocation efficiency Ψ{sub rlc}, and (3) the effective attenuation length L in XPS analysis were varied within reasonable limits until the calculated retention curves for 1 and 5 keV Ar in Si agreed with experimental data to better than 8%, using the same XPS sensitivity factor throughout. Results: w = 1.4 ± 0.1 nm, Ψ{sub rlc} = 6.6 ± 0.5, and L = 2.7 ± 0.2 nm. Combining experimental and calculated data, it was found that the Ar trapping efficiency of the damaged oxide is intimately correlated with the loss of oxygen. The calculated stationary areal densities of all retained Ar are compared with results obtained by high-resolution medium-energy ion scattering spectrometry. Attractive areas of future research in rare gas retention and nanobubble formation are sketched briefly.« less

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

PubMed

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

2017-08-15

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

Prediction of sub-surface 37Ar concentrations at locations in the Northwestern United States.

PubMed

Fritz, Bradley G; Aalseth, Craig E; Back, Henning O; Hayes, James C; Humble, Paul H; Ivanusa, Pavlo; Mace, Emily K

2018-01-01

The Comprehensive Nuclear-Test-Ban Treaty, which is intended to prevent nuclear weapon test explosions and any other nuclear explosions, includes a verification regime, which provides monitoring to identify potential nuclear explosions. The presence of elevated 37 Ar is one way to identify subsurface nuclear explosive testing. However, the naturally occurring formation of 37 Ar in the subsurface adds a complicating factor. Prediction of the naturally occurring concentration of 37 Ar can help to determine if a measured 37 Ar concentration is elevated relative to background. The naturally occurring 37 Ar background concentration has been shown to vary between less than 1 mBq/m 3 to greater than 100 mBq/m 3 (Riedmann and Purtschert, 2011). The purpose of this work was to enhance the understanding of the naturally occurring background concentrations of 37 Ar, allowing for better interpretation of results. To that end, we present and evaluate a computationally efficient model for predicting the average concentration of 37 Ar at any depth under transient barometric pressures. Further, measurements of 37 Ar concentrations in samples collected at multiple locations are provided as validation of the concentration prediction model. The model is shown to compare favorably with concentrations of 37 Ar measured at multiple locations in the Northwestern United States. Copyright © 2017 Elsevier Ltd. All rights reserved.

Iron-catalyzed oxidative biaryl cross-couplings via mixed diaryl titanates: significant influence of the order of combining aryl Grignard reagents with titanate.

PubMed

Liu, Kun Ming; Wei, Juan; Duan, Xin Fang

2015-03-18

The mixed diaryl titanates were used for the first time to modify the reactivity of two aryl Grignard reagents. Two titanate intermediates, Ar[Ar'Ti(OR)3]MgX and Ar'[ArTi(OR)3]MgX, formed via alternating the sequence of combining Grignard reagents with ClTi(OR)3 showed a significant reactivity difference. Taking advantage of such different reactivity, two highly structurally similar aryl groups could be facilely assembled through iron-catalyzed oxidative cross-couplings using oxygen as the oxidant.

Copy number of ArsR reporter plasmid determines its arsenite response and metal specificity.

PubMed

Fang, Yun; Zhu, Chunjie; Chen, Xingjuan; Wang, Yan; Xu, Meiying; Sun, Guoping; Guo, Jun; Yoo, Jinnon; Tie, Cuijuan; Jiang, Xin; Li, Xianqiang

2018-05-16

The key component in bacteria-based biosensors is a transcriptional reporter employed to monitor induction or repression of a reporter gene corresponding to environmental change. In this study, we made a series of reporters in order to achieve highly sensitive detection of arsenite. From these reporters, two biosensors were developed by transformation of Escherichia coli DH5α with pLHPars9 and pLLPars9, consisting of either a high or low copy number plasmid, along with common elements of ArsR-luciferase fusion and addition of two binding sequences, one each from E. coli and Acidithiobacillus ferrooxidans chromosome, in front of the R773 ArsR operon. Both of them were highly sensitive to arsenite, with a low detection limit of 0.04 μM arsenite (~ 5 μg/L). They showed a wide dynamic range of detection up to 50 μM using high copy number pLHPars9 and 100 μM using low copy number pLLPars9. Significantly, they differ in metal specificity, pLLPars9 more specific to arsenite, while pLHPars9 to both arsenite and antimonite. The only difference between pLHPars9 and pLLPars9 is their copy numbers of plasmid and corresponding ratios of ArsR to its binding promoter/operator sequence. Therefore, we propose a working model in which DNA bound-ArsR is different from its free form in metal specificity.

Magnetohydrodynamic Simulations for Studying Solar Flare Trigger Mechanism

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

Muhamad, J.; Kusano, K.; Inoue, S.

In order to understand the flare trigger mechanism, we conduct three-dimensional magnetohydrodynamic simulations using a coronal magnetic field model derived from data observed by the Hinode satellite. Several types of magnetic bipoles are imposed into the photospheric boundary of the Nonlinear Force-free Field model of Active Region (AR) NOAA 10930 on 2006 December 13, to investigate what kind of magnetic disturbance may trigger the flare. As a result, we confirm that certain small bipole fields, which emerge into the highly sheared global magnetic field of an AR, can effectively trigger a flare. These bipole fields can be classified into twomore » groups based on their orientation relative to the polarity inversion line: the so-called opposite polarity, and reversed shear structures, as suggested by Kusano et al. We also investigate the structure of the footpoints of reconnected field lines. By comparing the distribution of reconstructed field lines and observed flare ribbons, the trigger structure of the flare can be inferred. Our simulation suggests that the data-constrained simulation, taking into account both the large-scale magnetic structure and small-scale magnetic disturbance (such as emerging fluxes), is a good way to discover a flare-producing AR, which can be applied to space weather prediction.« less

Autoregressive model in the Lp norm space for EEG analysis.

PubMed

Li, Peiyang; Wang, Xurui; Li, Fali; Zhang, Rui; Ma, Teng; Peng, Yueheng; Lei, Xu; Tian, Yin; Guo, Daqing; Liu, Tiejun; Yao, Dezhong; Xu, Peng

2015-01-30

The autoregressive (AR) model is widely used in electroencephalogram (EEG) analyses such as waveform fitting, spectrum estimation, and system identification. In real applications, EEGs are inevitably contaminated with unexpected outlier artifacts, and this must be overcome. However, most of the current AR models are based on the L2 norm structure, which exaggerates the outlier effect due to the square property of the L2 norm. In this paper, a novel AR object function is constructed in the Lp (p≤1) norm space with the aim to compress the outlier effects on EEG analysis, and a fast iteration procedure is developed to solve this new AR model. The quantitative evaluation using simulated EEGs with outliers proves that the proposed Lp (p≤1) AR can estimate the AR parameters more robustly than the Yule-Walker, Burg and LS methods, under various simulated outlier conditions. The actual application to the resting EEG recording with ocular artifacts also demonstrates that Lp (p≤1) AR can effectively address the outliers and recover a resting EEG power spectrum that is more consistent with its physiological basis. Copyright © 2014 Elsevier B.V. All rights reserved.

-(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia.

PubMed

Cregan, E F; Peeling, J; Corbett, D; Buchan, A M; Saunders, J; Auer, R N; Gao, M; Mccarthy, D J; Eisman, M S; Campbell, T M; Murray, R J; Stagnitto, M L; Palmer, G C

1997-12-01

[(S)-Alpha-phenyl-2-pyridine-ethanamine dihydrochloride] (ARL 15896AR) is a low affinity uncompetitive N-methyl-D-aspartic acid receptor antagonist that was tested in animal models of anoxia and ischemia. Pretreatment of rodents with ARL 15896AR extended survival time during exposure to hypoxia. With the rat four-vessel occlusion model of global ischemia (20 min), oral dosing commencing at reflow, resulted in significant protection of the CA1 hippocampal neurons. ARL 15896AR was, however, ineffective in the rat two-vessel occlusion model and in the gerbil models of forebrain ischemia, the latter due to an inability to attain suitable plasma levels. In the spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) (2 hr plus 22 hr reflow), acute dosing with ARL 15896AR (i.p.) beginning from 30 min before or up to 1 hr post-MCAO significantly reduced cortical infarct volume. The ability of ARL 15896AR to influence infarct size, as well as functional correlates was examined in SHR after 90 min of MCAO. T2 weighted magnetic resonance images taken at 2 and 6 days post-MCAO revealed significantly smaller lesion sizes in the group receiving injections with ARL 15896AR beginning 30 min after occlusion. Spontaneously hypertensive rats were subsequently tested (30-42 days post-MCAO) and found to be deficient in skilled use of the forepaws (staircase test). The contralateral forepaw was most severely impaired, however, ARL 15896AR treatment prevented motor impairment in only the ipsilateral forepaw. Histopathological examination of cortical infarct size was unremarkable between treated and control rats. The findings indicate that ARL 15896AR exhibits neuroprotection in global and focal models of ischemia

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

PubMed Central

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

2014-01-01

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

Mathematical modeling physiological effects of the overexpression of β2-adrenoceptors in mouse ventricular myocytes.

PubMed

Rozier, Kelvin; Bondarenko, Vladimir E

2018-03-01

Transgenic (TG) mice overexpressing β 2 -adrenergic receptors (β 2 -ARs) demonstrate enhanced myocardial function, which manifests in increased basal adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo. To gain insights into the mechanisms of these effects, we developed a comprehensive mathematical model of the mouse ventricular myocyte overexpressing β 2 -ARs. We found that most of the β 2 -ARs are active in control conditions in TG mice. The simulations describe the dynamics of major signaling molecules in different subcellular compartments, increased basal adenylyl cyclase activity, modifications of action potential shape and duration, and the effects on L-type Ca 2+ current and intracellular Ca 2+ concentration ([Ca 2+ ] i ) transients upon stimulation of β 2 -ARs in control, after the application of pertussis toxin, upon stimulation with a specific β 2 -AR agonist zinterol, and upon stimulation with zinterol in the presence of pertussis toxin. The model also describes the effects of the β 2 -AR inverse agonist ICI-118,551 on adenylyl cyclase activity, action potential, and [Ca 2+ ] i transients. The simulation results were compared with experimental data obtained in ventricular myocytes from TG mice overexpressing β 2 -ARs and with simulation data on wild-type mice. In conclusion, a new comprehensive mathematical model was developed that describes multiple experimental data on TG mice overexpressing β 2 -ARs and can be used to test numerous hypotheses. As an example, using the developed model, we proved the hypothesis of the major contribution of L-type Ca 2+ current to the changes in the action potential and [Ca 2+ ] i transient upon stimulation of β 2 -ARs with zinterol. NEW & NOTEWORTHY We developed a new mathematical model for transgenic mouse ventricular myocytes overexpressing β 2 -adrenoceptors that describes the experimental findings in transgenic mice. The model reveals mechanisms of the differential effects of stimulation of β 2 -adrenoceptors in wild-type and transgenic mice overexpressing β 2 -adrenoceptors.

High order harmonics anomaly of jet screech

NASA Astrophysics Data System (ADS)

Chen, Zhe; Wu, Jiu Hui; Ren, A.-Dan; Chen, Xin

2018-05-01

Imperfectly expanded supersonic jets under strong screech could generate both fundamental screech tones and multiple tones at the harmonics of the fundamental frequency. The paper compares the fundamental frequency of jets from both AR = 3 (Aspect Ratio) and AR = 4 rectangular nozzles, and conducts analysis of harmonics on Sound Pressure Level (SPL) spectrums of jet noise. The research suggests that the fundamental frequency of the first two- or three-order harmonics increases when the Nozzle Pressure Ratio (NPR) decreases, whereas the highest order harmonic decreases when the NPR decreases. Besides, the paper also observes the differences between the highest order harmonics and other harmonics that have never been reported before. Further analysis on flow field schlieren of AR = 3 nozzle indicates that the highest order harmonic is the outcome of interaction between second shock-cell and nonlinear instable wave. The revolution of these high order harmonics can provide guidance for the prevention of small-scale structure fatigue damage. Moreover, the distribution test of the noises is also carried out to verify the high order harmonics anomaly, and indicate that the jet noise spreads mainly towards downstream while screech towards upstream. In addition, the broadband shock-associated noise spreads vertical to the jet flow and exhibits the feature of directivity.

Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep.

PubMed

Modarreszadeh, M; Bruce, E N; Gothe, B

1990-08-01

We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second-order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low-frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown.

Ultrahigh resolution drug design I: details of interactions in human aldose reductase-inhibitor complex at 0.66 A.

PubMed

Howard, E I; Sanishvili, R; Cachau, R E; Mitschler, A; Chevrier, B; Barth, P; Lamour, V; Van Zandt, M; Sibley, E; Bon, C; Moras, D; Schneider, T R; Joachimiak, A; Podjarny, A

2004-06-01

The first subatomic resolution structure of a 36 kDa protein [aldose reductase (AR)] is presented. AR was cocrystallized at pH 5.0 with its cofactor NADP+ and inhibitor IDD 594, a therapeutic candidate for the treatment of diabetic complications. X-ray diffraction data were collected up to 0.62 A resolution and treated up to 0.66 A resolution. Anisotropic refinement followed by a blocked matrix inversion produced low standard deviations (<0.005 A). The model was very well ordered overall (CA atoms' mean B factor is 5.5 A2). The model and the electron-density maps revealed fine features, such as H-atoms, bond densities, and significant deviations from standard stereochemistry. Other features, such as networks of hydrogen bonds (H bonds), a large number of multiple conformations, and solvent structure were also better defined. Most of the atoms in the active site region were extremely well ordered (mean B approximately 3 A2), leading to the identification of the protonation states of the residues involved in catalysis. The electrostatic interactions of the inhibitor's charged carboxylate head with the catalytic residues and the charged coenzyme NADP+ explained the inhibitor's noncompetitive character. Furthermore, a short contact involving the IDD 594 bromine atom explained the selectivity profile of the inhibitor, important feature to avoid toxic effects. The presented structure and the details revealed are instrumental for better understanding of the inhibition mechanism of AR by IDD 594, and hence, for the rational drug design of future inhibitors. This work demonstrates the capabilities of subatomic resolution experiments and stimulates further developments of methods allowing the use of the full potential of these experiments. Copyright 2004 Wiley-Liss, Inc.

Matrix effect on vibrational frequencies: Experiments and simulations for HCl and HNgCl (Ng = Kr and Xe)

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

Kalinowski, Jaroslaw; Räsänen, Markku; Lignell, Antti

2014-03-07

We study the environmental effect on molecules embedded in noble-gas (Ng) matrices. The experimental data on HXeCl and HKrCl in Ng matrices is enriched. As a result, the H−Xe stretching bands of HXeCl are now known in four Ng matrices (Ne, Ar, Kr, and Xe), and HKrCl is now known in Ar and Kr matrices. The order of the H−Xe stretching frequencies of HXeCl in different matrices is ν(Ne) < ν(Xe) < ν(Kr) < ν(Ar), which is a non-monotonous function of the dielectric constant, in contrast to the “classical” order observed for HCl: ν(Xe) < ν(Kr) < ν(Ar) < ν(Ne).more » The order of the H−Kr stretching frequencies of HKrCl is consistently ν(Kr) < ν(Ar). These matrix effects are analyzed theoretically by using a number of quantum chemical methods. The calculations on these molecules (HCl, HXeCl, and HKrCl) embedded in single Ng{sup ′} layer cages lead to very satisfactory results with respect to the relative matrix shifts in the case of the MP4(SDQ) method whereas the B3LYP-D and MP2 methods fail to fully reproduce these experimental results. The obtained order of frequencies is discussed in terms of the size available for the Ng hydrides in the cages, probably leading to different stresses on the embedded molecule. Taking into account vibrational anharmonicity produces a good agreement of the MP4(SDQ) frequencies of HCl and HXeCl with the experimental values in different matrices. This work also highlights a number of open questions in the field.« less

Multidiffusion mechanisms for noble gases (He, Ne, Ar) in silicate glasses and melts in the transition temperature domain: Implications for glass polymerization

NASA Astrophysics Data System (ADS)

Amalberti, Julien; Burnard, Pete; Laporte, Didier; Tissandier, Laurent; Neuville, Daniel R.

2016-01-01

Noble gases are ideal probes to study the structure of silicate glasses and melts as the modifications of the silicate network induced by the incorporation of noble gases are negligible. In addition, there are systematic variations in noble gas atomic radii and several noble gas isotopes with which the influence of the network itself on diffusion may be investigated. Noble gases are therefore ideally suited to constrain the time scales of magma degassing and cooling. In order to document noble gas diffusion behavior in silicate glass, we measured the diffusivities of three noble gases (4He, 20Ne and 40Ar) and the isotopic diffusivities of two Ar isotopes (36Ar and 40Ar) in two synthetic basaltic glasses (G1 and G2; 20Ne and 36Ar were only measured in sample G1). These new diffusion results are used to re-interpret time scales of the acquisition of fractionated atmospheric noble gas signatures in pumices. The noble gas bearing glasses were synthesized by exposing the liquids to high noble gas partial pressures at high temperature and pressure (1750-1770 K and 1.2 GPa) in a piston-cylinder apparatus. Diffusivities were measured by step heating the glasses between 423 and 1198 K and measuring the fraction of gas released at each temperature step by noble gas mass spectrometry. In addition we measured the viscosity of G1 between 996 and 1072 K in order to determine the precise glass transition temperature and to estimate network relaxation time scales. The results indicate that, to a first order, that the smaller the size of the diffusing atom, the greater its diffusivity at a given temperature: D(He) > D(Ne) > D(Ar) at constant T. Significantly, the diffusivities of the noble gases in the glasses investigated do not display simple Arrhenian behavior: there are well-defined departures from Arrhenian behavior which occur at lower temperatures for He than for Ne or Ar. We propose that the non-Arrhenian behavior of noble gases can be explained by structural modifications of the silicate network itself as the glass transition temperature is approached: as the available free volume (available site for diffusive jumps) is modified, noble gas diffusion is no longer solely temperature-activated but also becomes sensitive to the kinetics of network rearrangements. The non-Arrhenian behavior of noble gas diffusion close to Tg is well described by a modified Vogel-Tammann-Fulcher (VTF) equation: Finally, our step heating diffusion experiments suggest that at T close to Tg, noble gas isotopes may suffer kinetic fractionation at a degree larger than that predicted by Graham's law. In the case of 40Ar and 36Ar, the traditional assumption based on Graham's law is that the ratio D40Ar/D36Ar should be equal to 0.95 (the square root of the ratio of the mass of 36Ar over the mass of 40Ar). In our experiment with glass G1, D40Ar/D36Ar rapidly decreased with decreasing temperature, from near unity (0.98 ± 0.14) at T > 1040 K to 0.76 when close to Tg (T = 1003 K). Replicate experiments are needed to confirm the strong kinetic fractionation of heavy noble gases close to the transition temperature.

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

A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

PubMed

Bunyavanich, Supinda; Shargorodsky, Josef; Celedón, Juan C

2011-06-01

There is a significant genetic contribution to allergic rhinitis (AR). Genetic association studies for AR have been performed, but varying results make it challenging to decipher the overall potential effect of specific variants. The Th2 pathway plays an important role in the immunological development of AR. We performed meta-analyses of genetic association studies of variants in Th2 pathway genes and AR. PubMed and Phenopedia were searched by double extraction for original studies on Th2 pathway-related genetic polymorphisms and their associations with AR. A meta-analysis was conducted on each genetic polymorphism with data meeting our predetermined selection criteria. Analyses were performed using both fixed and random effects models, with stratification by age group, ethnicity, and AR definition where appropriate. Heterogeneity and publication bias were assessed. Six independent studies analyzing three candidate polymorphisms and involving a total of 1596 cases and 2892 controls met our inclusion criteria. Overall, the A allele of IL13 single nucleotide polymorphism (SNP) rs20541 was associated with increased odds of AR (estimated OR=1.2; 95% CI 1.1-1.3, p-value 0.004 in fixed effects model, 95% CI 1.0-1.5, p-value 0.056 in random effects model). The A allele of rs20541 was associated with increased odds of AR in mixed age groups using both fixed effects and random effects modeling. IL13 SNP rs1800925 and IL4R SNP 1801275 did not demonstrate overall associations with AR. We conclude that there is evidence for an overall association between IL13 SNP rs20541 and increased risk of AR, especially in mixed-age populations. © 2011 John Wiley & Sons A/S.

Comparison of Global Cloud Fraction and TOA Radiation Budgets between the NASA GISS AR5 GCM Simulations and CERES-MODIS Observations

NASA Astrophysics Data System (ADS)

Stanfield, R. E.; Dong, X.; Xi, B.; Del Genio, A. D.; Minnis, P.; Doelling, D.; Loeb, N. G.

2011-12-01

To better advise policymakers, it is necessary for climate models to provide credible predictions of future climates. Meeting this goal requires climate models to successfully simulate the present and past climates. The past, current and future Earth climate has been simulated by the NASA GISS ModelE climate model and has been summarized by the Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC, AR4, 2007). New simulations from the updated AR5 version of the NASA GISS ModelE GCM have been released to the public community and will be included in the IPCC AR5 ensemble of simulations. Due to the recent nature of these simulations, however, they have yet to be extensively validated against observations. To evaluate the GISS AR5 simulated global clouds and TOA radiation budgets, we have collected and processed the NASA CERES and MODIS observations during the period 2000-2005. In detail, the 1ox1o resolution monthly averaged SYN1 product has been used with combined observations from both Terra and Aqua satellites, and degraded to a 2ox2.5o grid box to match the GCM spatial resolution. These observations are temporally interpolated and fit to data from geostationary satellites to provide time continuity. The GISS AR5 products were downloaded from the CMIP5 (Coupled Model Intercomparison Project Phase 5) for the IPCC-AR5. Preliminary comparisons between GISS AR5 simulations and CERES-MODIS observations have shown that although their annual and seasonal mean CFs agree within a few percent, there are significant differences in several climatic regions. For example, the modeled CFs have positive biases in the Arctic, Antarctic, Tropics, and Sahara Desert, but negative biases over the southern middle latitudes (30-65 oS). The OLR, albedo and NET radiation comparisons are similar to the CF comparison.

A closer look at 40Ar/39Ar systematics of illite, recoil, retention ages, total gas ages, and a new correction method

NASA Astrophysics Data System (ADS)

Fitz-Diaz, E.; Hall, C. M.; van der Pluijm, B.

2013-12-01

One of the fundamentals of 40Ar-39Ar systematics of illite considers the effects of 39Ar recoil (ejection of 39Ar from tiny illite crystallites during the nuclear reaction 39K(n,p)39Ar), for which sample vacuum encapsulation prior to irradiation has been used since the 1990's. This technique separately measures the fraction of recoiled 39Ar and the Ar (39Ar and 40Ar) retained within illite crystals as they degas during step heating in vacuum. Total-gas ages (TGA) are calculated by using both recoiled and retained argon, while retention ages (RA) only involve retained Ar. Observations in numerous natural examples have shown that TGA fit stratigraphic constraints of geological processes when the average illite crystallite thickness (ICT) is smaller than 10nm, and that RA better matches these constrains for larger ICTs. Illite crystals with ICT >50nm show total gas and retention ages within a few My and they are identical, within analytical error, when ICT exceeds 150nm. We propose a new age correction that takes into account the average ICT and corresponding recoil for a sample , with such corrected ages (XCA) lying between the TGA and RA end-member ages. We apply this correction to samples containing one generation of illite and it particularly affects illite populations formed in the anchizone, with typical ICT values between 10-40nm. We analyzed bentonitic samples (S1, S2 and S3) from sites in Cretaceous carbonates in the front of the Monterrey salient in northern Mexico. Four size fractions (<0.05, 0.05-0.2, 0.2-1 & 1-2 μm) were separated, analyzed with XRD and dated by Ar-Ar. XRD analysis provides mineralogic characterization, illite polytype quantification, and illite crystallite thickness (ICT) determination using half-height peak width (illite crystallinity) and the Scherrer equation. All samples contain illite as the main mineral phase, ICT values between 8-27nm, from fine to coarser grain size fractions. Ages show a range in TGA among the different size fractions of S1, S2 and S3, respectively: 46-49, 36-43 and 40-52 My) and RA (54-64, 47-52 and 53-54 My. XCA calculations produce tighter constrained ranges (53-57, 45.5-48.5 and 49-52 My) with an overall average 51.1Ma×3.9 My. In the ICT vs. apparent age plot, authigenic illite grains show a greater slope that is in general slightly positive for TGA, slightly negative for RA, but close to zero for XCA. In the ICT vs. XCA plot thinner crystallites shows more dispersion than thicker ones. In order to test if such dispersion in the age of the finer/thinner illite is due to a different formation history in each site or the result of retention capability, degassing spectra were modeled for site XCA averages and overall XCA average. The modeling shows that local site ages best match the measured spectra, instead of a single age for the combined sites. The closeness between experimental and artificial degassing patterns also supports the hypothesis that each sample preserves a single age population. All illite grains in these samples grew progressively during folding in a time window that is constrained by the three sites. Small and large grains represent the same population in each sample, representing progressive degrees of grain growth (Ostwald ripening).

Evaluation of Areas for Off-Road Recreational Motorcycle Use. Volume I. Evaluation Method.

DTIC Science & Technology

1980-11-01

PwaLgraph 7 of AR 2109, Environmental Considerations, states that the environmental and related impact , (of ()RRV use will be assessed according to AR...with only one or more aspects of the subject, i.e., noise, soil damage, impact on vegetation, trail development, user profiles. or environmental...specifically identified in the 1972 and 1977 Executive Orders and AR 210-9 others such as impact and maneuver areas are generally known to be in direct

[The expression and significance of chemokines eotaxin and RANTES in the rat model of allergic rhinitis].

PubMed

Tian, Cuiling; Lei, Xiaoping; Shui, Minhong; Zhang, Yanhong; Jia, Qianwei; Tu, Jing; Lian, Gang; Tang, Siquan

2014-07-01

To explore the expression and significance of Eotaxin and RANTES in the rat model of allergic rhinitis (AR). 20 female SD rats in 6-7 weeks were randomly divided into control group and AR group (n = 10, respectively). AR rat model was made with ovalbumin stimulation. To detect pathological changes in mucosa and chemokine Eotaxin, RANTES in their nasal and lung tissues after execution. Compared with the control group, Lung EOS cell counted higher in AR group and the difference was significant (P < 0.01); the AR rats nasal mucosa and lung tissue of Eotaxin, RANTES expression was significantly increased (P < 0.01). There exist high expression of Eotaxin, RANTES, infiltration of eosinophils in nasal and lung tissue of model rats with allergic rhinitis, inferring that the upper and lower respiratory tract inflammatory response has obvious consistency.

Comparative analysis of ArnCl2 (2 ? n ? 30) clusters taking into account molecular relaxation effects

NASA Astrophysics Data System (ADS)

Ferreira, G. G.; Borges, E.; Braga, J. P.; Belchior, J. C.

Cluster structures are discussed in a nonrigid analysis, using a modified minima search method based on stochastic processes and classical dynamics simulations. The relaxation process is taken into account considering the internal motion of the Cl2 molecule. Cluster structures are compared with previous works in which the Cl2 molecule is assumed to be rigid. The interactions are modeled using pair potentials: the Aziz and Lennard-Jones potentials for the Ar==Ar interaction, a Morse potential for the Cl==Cl interaction, and a fully spherical/anisotropic Morse-Spline-van der Waals (MSV) potential for the Ar==Cl interaction. As expected, all calculated energies are lower than those obtained in a rigid approximation; one reason may be attributed to the nonrigid contributions of the internal motion of the Cl2 molecule. Finally, the growing processes in molecular clusters are discussed, and it is pointed out that the growing mechanism can be affected due to the nonrigid initial conditions of smaller clusters such as ArnCl2 (n ? 4 or 5), which are seeds for higher-order clusters.

Localizing Tortoise Nests by Neural Networks.

PubMed

Barbuti, Roberto; Chessa, Stefano; Micheli, Alessio; Pucci, Rita

2016-01-01

The goal of this research is to recognize the nest digging activity of tortoises using a device mounted atop the tortoise carapace. The device classifies tortoise movements in order to discriminate between nest digging, and non-digging activity (specifically walking and eating). Accelerometer data was collected from devices attached to the carapace of a number of tortoises during their two-month nesting period. Our system uses an accelerometer and an activity recognition system (ARS) which is modularly structured using an artificial neural network and an output filter. For the purpose of experiment and comparison, and with the aim of minimizing the computational cost, the artificial neural network has been modelled according to three different architectures based on the input delay neural network (IDNN). We show that the ARS can achieve very high accuracy on segments of data sequences, with an extremely small neural network that can be embedded in programmable low power devices. Given that digging is typically a long activity (up to two hours), the application of ARS on data segments can be repeated over time to set up a reliable and efficient system, called Tortoise@, for digging activity recognition.

Assessment of simulated aerosol effective radiative forcings in the terrestrial spectrum

NASA Astrophysics Data System (ADS)

Heyn, Irene; Block, Karoline; Mülmenstädt, Johannes; Gryspeerdt, Edward; Kühne, Philipp; Salzmann, Marc; Quaas, Johannes

2017-01-01

In its fifth assessment report (AR5), the Intergovernmental Panel on Climate Change provides a best estimate of the effective radiative forcing (ERF) due to anthropogenic aerosol at -0.9 W m-2. This value is considerably weaker than the estimate of -1.2 W m-2 in AR4. A part of the difference can be explained by an offset of +0.2 W m-2 which AR5 added to all published estimates that only considered the solar spectrum, in order to account for adjustments in the terrestrial spectrum. We find that, in the CMIP5 multimodel median, the ERF in the terrestrial spectrum is small, unless microphysical effects on ice- and mixed-phase clouds are parameterized. In the latter case it is large but accompanied by a very strong ERF in the solar spectrum. The total adjustments can be separated into microphysical adjustments (aerosol "effects") and thermodynamic adjustments. Using a kernel technique, we quantify the latter and find that the rapid thermodynamic adjustments of water vapor and temperature profiles are small. Observation-based constraints on these model results are urgently needed.

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells

PubMed Central

Lee, Minjong; Jo, Ara; Lee, Seulki; Kim, Jong Bin; Chang, Young; Nam, Joon Yeul; Cho, Hyeki; Cho, Young Youn; Cho, Eun Ju; Lee, Jeong-Hoon; Yu, Su Jong; Yoon, Jung-Hwan

2017-01-01

Background & aims Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. Methods We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial–mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model. Results AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib. Conclusions These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC. PMID:28362858

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.

PubMed

Lee, Minjong; Jo, Ara; Lee, Seulki; Kim, Jong Bin; Chang, Young; Nam, Joon Yeul; Cho, Hyeki; Cho, Young Youn; Cho, Eun Ju; Lee, Jeong-Hoon; Yu, Su Jong; Yoon, Jung-Hwan; Kim, Yoon Jun

2017-01-01

Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial-mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model. AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib. These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.

Prediction of sub-surface 37 Ar concentrations at locations in the Northwestern United States

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

Fritz, Bradley G.; Aalseth, Craig E.; Back, Henning O.

The Comprehensive Nuclear Test-Ban Treaty, which is intended to prevent nuclear weapon testing, includes a verification regime, which provides monitoring to identify potential nuclear testing. The presence of elevated 37Ar is one way to identify subsurface nuclear testing. However, the naturally occurring formation of 37Ar in the subsurface adds a complicating factor. Prediction of the naturally occurring concentration of 37Ar can help to determine if a measured 37Ar concentration is elevated. The naturally occurring 37Ar background concentration has been shown to vary between less than 1 mBq/m3 to greater than 100 mBq/m3 (Riedmann and Purtschert 2011). Here, we evaluate amore » model for predicting the average concentration of 37Ar at any depth under transient barometric pressures, and compare it with measurements. This model is shown to compare favorably with concentrations of 37Ar measured at multiple locations in the Northwestern United States.« less

On the maximum-entropy/autoregressive modeling of time series

NASA Technical Reports Server (NTRS)

Chao, B. F.

1984-01-01

The autoregressive (AR) model of a random process is interpreted in the light of the Prony's relation which relates a complex conjugate pair of poles of the AR process in the z-plane (or the z domain) on the one hand, to the complex frequency of one complex harmonic function in the time domain on the other. Thus the AR model of a time series is one that models the time series as a linear combination of complex harmonic functions, which include pure sinusoids and real exponentials as special cases. An AR model is completely determined by its z-domain pole configuration. The maximum-entropy/autogressive (ME/AR) spectrum, defined on the unit circle of the z-plane (or the frequency domain), is nothing but a convenient, but ambiguous visual representation. It is asserted that the position and shape of a spectral peak is determined by the corresponding complex frequency, and the height of the spectral peak contains little information about the complex amplitude of the complex harmonic functions.

76 FR 771 - Reorganization/Expansion of Foreign-Trade Zone 14 Under Alternative Site Framework; Little Rock, AR

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Order No. 1729] Reorganization/Expansion of Foreign-Trade Zone 14 Under Alternative Site Framework; Little Rock, AR Pursuant to its authority under... the Little Rock Customs and Border [[Page 772

Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

PubMed

Ai, Si; Zheng, Jian; Chu, Ke-Dan; Zhang, Hong-Sheng

2015-06-01

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p <0.01). Treatments with low-dose Xingbi gel, high-dose Xingbi gel, and budesonide significantly reduced the ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts as compared to untreated AR model guinea pigs (p <0.01). Xingbi gel alleviates AR in part through inhibiting LTE4 and IgE production and reducing eosinophilia in the nasal mucosa.

A comparative study on the frequency effects of the electrical characteristics of the pulsed dielectric barrier discharge in He/O{sub 2} and in Ar/O{sub 2} at atmospheric pressure

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

Pan, Guangsheng; Tan, Zhenyu, E-mail: tzy@sdu.edu.cn; Pan, Jie

In this work, a comparative study on the frequency effects of the electrical characteristics of the pulsed dielectric barrier discharges in He/O{sub 2} and in Ar/O{sub 2} at atmospheric pressure has been performed by means of the numerical simulation based on a 1-D fluid model at frequencies below 100 kHz. The frequency dependences of the characteristic quantities of the discharges in the two gases have been systematically calculated and analyzed under the oxygen concentrations below 2%. The characteristic quantities include the discharge current density, the averaged electron density, the electric field, and the averaged electron temperature. Especially, the frequency effects onmore » the averaged particle densities of the reactive species have also been calculated. This work gives the following significant results. For the two gases, there are two bipolar discharges in one period of applied voltage pulse under the considered frequency range and oxygen concentrations, as occurred in the pure noble gases. The frequency affects the two discharges in He/O{sub 2}, but in Ar/O{sub 2}, it induces a strong effect only on the first discharge. For the first discharge in each gas, there is a characteristic frequency at which the characteristic quantities reach their respective minimum, and this frequency appears earlier for Ar/O{sub 2}. For the second discharge in Ar/O{sub 2}, the averaged electron density presents a slight variation with the frequency. In addition, the discharge in Ar/O{sub 2} is strong and the averaged electron temperature is low, compared to those in He/O{sub 2.} The total averaged particle density of the reactive species in Ar/O{sub 2} is larger than those in He/O{sub 2} by about one order of magnitude.« less

Vibrational dynamics of aniline(Ar)1 and aniline(CH4)1 clusters

NASA Astrophysics Data System (ADS)

Nimlos, M. R.; Young, M. A.; Bernstein, E. R.; Kelley, D. F.

1989-11-01

The first excited electronic state (S1) vibrational dynamics of aniline(Ar)1 and aniline(CH4)1 van der Waals (vdW) clusters have been studied using molecular jet and time resolved emission spectroscopic techniques. The rates of intramolecular vibrational energy redistribution (IVR) and vibrational predissociation (VP) as functions of vibrational energy are reported for both clusters. For vibrational energy in excess of the cluster binding energy, both clusters are observed to dissociate. The dispersed emission spectra of these clusters demonstrate that aniline(Ar)1 dissociates to all energetically accessible bare molecule states and that aniline(CH4)1 dissociates selectively to only the bare molecule vibrationless state. The emission kinetics show that in the aniline(Ar)1 case, the initially excited states have nanosecond lifetimes, and intermediate cluster states have very short lifetimes. In contrast, the initially excited aniline(CH4)1 states and other intermediate vibrationally excited cluster states are very short lived (<100 ps), and the intermediate cluster 00 state is observed. These results can be understood semiquantitatively in terms of an overall serial IVR/VP mechanism which consists of the following: (1) the rates of chromophore to vdW mode IVR are given by Fermi's golden rule, and the density of vdW vibrational states is the most important factor in determining the relative [aniline(Ar)1 vs aniline(CH4)1] rates of IVR; (2) IVR among the vdW modes is rapid; and (3) VP rates can be calculated by a restricted vdW mode phase space Rice-Ramsberger-Kassel-Marcus theory. Since the density of vdW states is three orders of magnitude greater for aniline(CH4)1 than aniline(Ar)1 at 700 cm-1, the model predicts that IVR is slow and rate limiting in aniline(Ar)1, whereas VP is slow and rate limiting in aniline(CH4)1. The agreement of these predictions with the experimental results is very good and is discussed in detail.

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD

NASA Astrophysics Data System (ADS)

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-01

In order to confirm the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar+ ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar+ ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar+ ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar+ ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar+ ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar+ ion state. As for vertically oriented few-layer graphene (VFG), Ar+ ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar+ ion bombardment, and these special NCMs are promising in many fields.

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.

Effect of the heat shock protein HSP27 on androgen receptor expression and function in prostate cancer cells.

PubMed

Stope, Matthias B; Schubert, Tina; Staar, Doreen; Rönnau, Cindy; Streitbörger, Andreas; Kroeger, Nils; Kubisch, Constanze; Zimmermann, Uwe; Walther, Reinhard; Burchardt, Martin

2012-06-01

Heat shock proteins (HSP) are involved in processes of folding, activation, trafficking and transcriptional activity of most steroid receptors including the androgen receptor (AR). Accumulating evidence links rising heat shock protein 27 (HSP27) levels with the development of castration-resistant prostate cancer. In order to study the functional relationship between HSP27 and the AR, we modulated the expression of the small heat shock protein HSP27 in human prostate cancer (PC) cell lines. HSP27 protein concentrations in LNCaP and PC-3 cells were modulated by over-expression or silencing of HSP27. The effects of HSP27 on AR protein and mRNA levels were monitored by Western blotting and quantitative RT-PCR. Treatment for the AR-positive LNCaP with HSP27-specific siRNA resulted in a down-regulation of AR levels. This down-regulation of protein was paralleled by a decrease in AR mRNA. Most interestingly, over-expression of HSP27 in PC-3 cells led to a significant increase in AR mRNA although the cells were unable to produce functional AR protein. The observation that HSP27 is involved in the regulation of AR mRNA by a yet unknown mechanism highlights the complexity of HSP27-AR signaling network.

Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD.

PubMed

Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

2017-11-24

In order to confirm the key role of Ar + ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar + ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar + ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar + ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar + ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar + ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar + ion state. As for vertically oriented few-layer graphene (VFG), Ar + ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar + ion bombardment, and these special NCMs are promising in many fields.

``Smoking From The Same Pipe": Developement of an 40Ar/39Ar Datting Intercalibration PIpette System (Invited)

NASA Astrophysics Data System (ADS)

Turrin, B. D.; Swisher, C. C.; Deino, A.; Hemming, S. R.; Hodges, K.; Renne, P. R.

2010-12-01

The precision and accuracy of Ar isotope ratio measurements is one of the main limiting factors in the uncertainties of an 40Ar/39Ar age. Currently, it is relatively common to measure Ar isotopic ratios to a precision of 1-2‰ or better on an intralaboratory basis. This level of analytical precision equates to a comparable level of precision (1-3‰) in the calculated age, depending on the extent of atmospheric Ar contamination, importance of nucleogenic interference corrections, and other factors. However, it has become clear that improving the precision of mass spectrometry is not the only bottleneck towards improving the accuracy and precision of 40Ar/39Ar dating in general. Rather, the most urgent issue is interlaboratory reproducibility. This became obvious in a recent EARTHTIME initiative undertaken to intercalibrate two commonly used 40Ar/39Ar standards [the Fish Canyon sanidine (FCs) and the Alder Creek sanidine (ACs)]. This effort revealed variations amongst laboratories (at the 1-2% level), an order of magnitude greater than the internal analytical precisions. To address these issues, we have proposed (to NSF) to construct two identical pipette systems loaded to identical starting pressures and with identical isotopic compositions. One pipette system will travel between participating 40Ar/39Ar labs and the second system will not travel and serve as the “Master” system to test for any fractionation or undocumented depletion of the traveling pipette system. In order to ensure delivery of uniform amounts of homogenous gas, the pipette system will be computer-controlled with preprogrammed routines and lockouts to prevent compromising the reservoirs. The pipette systems will deliver three gas samples with different isotopic ratios at two different pressures/concentrations. One pipette bulb will be of atmospheric isotopic composition, and the other two pipette bulbs will have 40Ar*/39ArK ratios corresponding to co-irradiated ACs and FCs fixed by their relative ages at ~1:23.6. A pipette system will permit the participating labs to measure gas samples with exactly the same isotopic composition(s) and similar gas volumes. Measuring the same gas controls the variables such as 1) sample heterogeneity or experimental artifacts arising from neutron dosage; 2) incomplete degassing and the possibility of isotopic fractionation of Ar; and 3) problems related to isobaric interferences from e.g. hydrocarbons or HCl. By fixing these variables, the influence of different data reduction protocols can be assessed. In addition, measuring gas samples with fixed isotopic ratios at different pressures/concentrations will also test the pressure effects on ion source and/or detector linearity.

Xenocrysts and antecrysts and their effect on the precision of 40Ar/39Ar dates of explosive volcanic eruption

NASA Astrophysics Data System (ADS)

Smith, V.; Mark, D.; Blockley, S.; Weh, A.

2010-12-01

Evolved melts that fuel large explosive eruptions encounter, and are often generated through melting, crystal-rich parts of the magmatic system that fed previous eruptions. This results in many antecrysts being incorporated into the magma prior to eruption. In addition, many xenocrysts are entrained during eruption through conduit excavation. Combining all these crystal populations produces 40Ar/39Ar dates with wide-ranges, such as those that are often reported in the literature. In order to gain very precise dates of volcanic events it is thus necessary to assess whether antecrysts and xenocrysts effect the precision of the dates, and establish ways to reduce these components. Here we use the deposits of the ~11 ka Ulleung-Oki eruption from the alkaline volcanic island of Ulleung, situated 130 km east of the Korean peninsula. The eruption deposits are widely dispersed and found in the Suigetsu lake sequence from central Japan. A precise date of the tephra would help with construction of the terrestrial radiocarbon calibration curve that spans back to the limit of radiocarbon dating (~50 ka). The new calibration model is currently being constructed using varve chronology (annual layer counting) and >600 14C determinations of terrestrial macrofossils*. However, the annual layers stop shortly after the 2 cm-thick Ulleung-Oki tephra. Precise dates of this volcanic event using a method that is independent of radiocarbon dating, would help validate the chronology of the core, and test the validity of the radiocarbon calibration curve. The tephra in the core has been correlated to proximal deposits using major and trace element composition (determined using an electron microprobe and LA-ICPMS) of the glass shards that comprise the distal ash. The proximal Ulleung-Oki eruption deposits are sandine-rich with crystals that range from ~80 microns to a few millimetres in size. These are likely to be a mixture of phenocrysts, antecrysts and xenocrysts. In order to get a very precise age on a relatively young eruption (~11 ka) we carried out >70 40Ar/39Ar dates of crystals. The sanidines were extracted from individual large pumices that were fragmented using selFrag so that the crystals remained intact. The crystals were then split into different size ranges prior to analysis on a high-sensitivity multicollector noble gas mass spectrometer (ARGUS). This approach allows us to assess how the incorporation of antecrysts and xenocrysts effect 40Ar/39Ar dates. Here we present the age ranges and discuss the results. *Research being carried out by members of the NERC funded Suigetsu 2006 Project led by Takeshi Nakagawa, Newcastle University, UK (http://www.suigetsu.org/)

Forecasting Tehran stock exchange volatility; Markov switching GARCH approach

NASA Astrophysics Data System (ADS)

Abounoori, Esmaiel; Elmi, Zahra (Mila); Nademi, Younes

2016-03-01

This paper evaluates several GARCH models regarding their ability to forecast volatility in Tehran Stock Exchange (TSE). These include GARCH models with both Gaussian and fat-tailed residual conditional distribution, concerning their ability to describe and forecast volatility from 1-day to 22-day horizon. Results indicate that AR(2)-MRSGARCH-GED model outperforms other models at one-day horizon. Also, the AR(2)-MRSGARCH-GED as well as AR(2)-MRSGARCH-t models outperform other models at 5-day horizon. In 10 day horizon, three models of AR(2)-MRSGARCH outperform other models. Concerning 22 day forecast horizon, results indicate no differences between MRSGARCH models with that of standard GARCH models. Regarding Risk management out-of-sample evaluation (95% VaR), a few models seem to provide reasonable and accurate VaR estimates at 1-day horizon, with a coverage rate close to the nominal level. According to the risk management loss functions, there is not a uniformly most accurate model.

Blockade of adenosine A2A receptor enhances CD8+ T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma.

PubMed

Ma, Si-Rui; Deng, Wei-Wei; Liu, Jian-Feng; Mao, Liang; Yu, Guang-Tao; Bu, Lin-Lin; Kulkarni, Ashok B; Zhang, Wen-Feng; Sun, Zhi-Jun

2017-06-07

Cancer immunotherapy offers a promising approach in cancer treatment. The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. To date, the role of A2AR in head and neck squamous cell carcinoma (HNSCC) has not been investigated. Here, we sought to explore the expression and immunotherapeutic value of A2AR blockade in HNSCC. The expression of A2AR was evaluated by immunostaining in 43 normal mucosae, 48 dysplasia and 165 primary HNSCC tissues. The immunotherapeutic value of A2AR blockade was assessed in vivo in genetically defined immunocompetent HNSCC mouse model. Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status. Elevated A2AR expression was also detected in recurrent HNSCC and HNSCC tissues with induction chemotherapy. The expression of A2AR was found to be significantly correlated with HIF-1α, CD73, CD8 and Foxp3. Furthermore, the increased population of CD4 + Foxp3 + regulatory T cells (Tregs), which partially expressed A2AR, was observed in an immunocompetent mouse model that spontaneously develops HNSCC. Pharmacological blockade of A2AR by SCH58261 delayed the tumor growth in the HNSCC mouse model. Meanwhile, A2AR blockade significantly reduced the population of CD4 + Foxp3 + Tregs and enhanced the anti-tumor response of CD8 + T cells. These results offer a preclinical proof for the administration of A2AR inhibitor on prophylactic experimental therapy of HNSCC and suggest that A2AR blockade can be a potential novel strategy for HNSCC immunotherapy.

On Allometry Relations

NASA Astrophysics Data System (ADS)

West, Damien; West, Bruce J.

2012-07-01

There are a substantial number of empirical relations that began with the identification of a pattern in data; were shown to have a terse power-law description; were interpreted using existing theory; reached the level of "law" and given a name; only to be subsequently fade away when it proved impossible to connect the "law" with a larger body of theory and/or data. Various forms of allometry relations (ARs) have followed this path. The ARs in biology are nearly two hundred years old and those in ecology, geophysics, physiology and other areas of investigation are not that much younger. In general if X is a measure of the size of a complex host network and Y is a property of a complex subnetwork embedded within the host network a theoretical AR exists between the two when Y = aXb. We emphasize that the reductionistic models of AR interpret X and Y as dynamic variables, albeit the ARs themselves are explicitly time independent even though in some cases the parameter values change over time. On the other hand, the phenomenological models of AR are based on the statistical analysis of data and interpret X and Y as averages to yield the empirical AR: = ab. Modern explanations of AR begin with the application of fractal geometry and fractal statistics to scaling phenomena. The detailed application of fractal geometry to the explanation of theoretical ARs in living networks is slightly more than a decade old and although well received it has not been universally accepted. An alternate perspective is given by the empirical AR that is derived using linear regression analysis of fluctuating data sets. We emphasize that the theoretical and empirical ARs are not the same and review theories "explaining" AR from both the reductionist and statistical fractal perspectives. The probability calculus is used to systematically incorporate both views into a single modeling strategy. We conclude that the empirical AR is entailed by the scaling behavior of the probability density, which is derived using the probability calculus.

Augmented reality in gynecologic surgery: evaluation of potential benefits for myomectomy in an experimental uterine model.

PubMed

Bourdel, Nicolas; Collins, Toby; Pizarro, Daniel; Bartoli, Adrien; Da Ines, David; Perreira, Bruno; Canis, Michel

2017-01-01

Augmented Reality (AR) is a technology that can allow a surgeon to see subsurface structures. This works by overlaying information from another modality, such as MRI and fusing it in real time with the endoscopic images. AR has never been developed for a very mobile organ like the uterus and has never been performed for gynecology. Myomas are not always easy to localize in laparoscopic surgery when they do not significantly change the surface of the uterus, or are at multiple locations. To study the accuracy of myoma localization using a new AR system compared to MRI-only localization. Ten residents were asked to localize six myomas (on a uterine model into a laparoscopic box) when either using AR or in conditions that simulate a standard method (only the MRI was available). Myomas were randomly divided in two groups: the control group (MRI only, AR not activated) and the AR group (AR activated). Software was used to automatically measure the distance between the point of contact on the uterine surface and the myoma. We compared these distances to the true shortest distance to obtain accuracy measures. The time taken to perform the task was measured, and an assessment of the complexity was performed. The mean accuracy in the control group was 16.80 mm [0.1-52.2] versus 0.64 mm [0.01-4.71] with AR. In the control group, the mean time to perform the task was 18.68 [6.4-47.1] s compared to 19.6 [3.9-77.5] s with AR. The mean score of difficulty (evaluated for each myoma) was 2.36 [1-4] versus 0.87 [0-4], respectively, for the control and the AR group. We developed an AR system for a very mobile organ. This is the first user study to quantitatively evaluate an AR system for improving a surgical task. In our model, AR improves localization accuracy.

The Emotion Recognition System Based on Autoregressive Model and Sequential Forward Feature Selection of Electroencephalogram Signals

PubMed Central

Hatamikia, Sepideh; Maghooli, Keivan; Nasrabadi, Ali Motie

2014-01-01

Electroencephalogram (EEG) is one of the useful biological signals to distinguish different brain diseases and mental states. In recent years, detecting different emotional states from biological signals has been merged more attention by researchers and several feature extraction methods and classifiers are suggested to recognize emotions from EEG signals. In this research, we introduce an emotion recognition system using autoregressive (AR) model, sequential forward feature selection (SFS) and K-nearest neighbor (KNN) classifier using EEG signals during emotional audio-visual inductions. The main purpose of this paper is to investigate the performance of AR features in the classification of emotional states. To achieve this goal, a distinguished AR method (Burg's method) based on Levinson-Durbin's recursive algorithm is used and AR coefficients are extracted as feature vectors. In the next step, two different feature selection methods based on SFS algorithm and Davies–Bouldin index are used in order to decrease the complexity of computing and redundancy of features; then, three different classifiers include KNN, quadratic discriminant analysis and linear discriminant analysis are used to discriminate two and three different classes of valence and arousal levels. The proposed method is evaluated with EEG signals of available database for emotion analysis using physiological signals, which are recorded from 32 participants during 40 1 min audio visual inductions. According to the results, AR features are efficient to recognize emotional states from EEG signals, and KNN performs better than two other classifiers in discriminating of both two and three valence/arousal classes. The results also show that SFS method improves accuracies by almost 10-15% as compared to Davies–Bouldin based feature selection. The best accuracies are %72.33 and %74.20 for two classes of valence and arousal and %61.10 and %65.16 for three classes, respectively. PMID:25298928

78 FR 62584 - Certain Lined Paper Products From India: Preliminary Results of Countervailing Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... From India: Preliminary Results of Countervailing Duty Administrative Review; Calendar Year 2011 AGENCY... (CVD) order on certain lined paper products from India. The period of review (POR) is January 1, 2011.... Printing & Packaging India Pvt. Ltd. (AR Printing). We have preliminarily determined that AR Printing...

Neuroprotection by caffeine in the MPTP model of Parkinson’s disease and its dependence on adenosine A2A receptors

PubMed Central

Xu, Kui; Di Luca, Daniel Garbin; Orrú, Marco; Xu, Yuehang; Chen, Jiang-Fan; Schwarzschild, Michael A.

2016-01-01

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of Parkinson’s disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine’s neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on MPTP neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in CNS cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25 mg/kg ip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine’s locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. PMID:26905951

Kinetic analysis of rare gas metastable production and optically pumped Xe lasers

NASA Astrophysics Data System (ADS)

Demyanov, A. V.; Kochetov, I. V.; Mikheyev, P. A.; Azyazov, V. N.; Heaven, M. C.

2018-01-01

Optically pumped all-rare-gas lasers use metastable rare gas atoms as the lasing species in mixtures with He or Ar buffer gas. The metastables are generated in a glow discharge, and we report model calculations for the optimal production of Ne*, Ar*, Kr* and Xe*. Discharge efficiency was estimated by solving the Boltzmann equation. Laser efficiency, gain and output power of the CW optically pumped Xe laser were assessed as functions of heavier rare gas content, pressure, optical pump intensity and the optical path length. It was found that, for efficient operation the heavier rare gas content has to be of the order of one percent or less, and the total pressure—in the range 0.3-1.5 atm. Output power and specific discharge power increase approximately linearly with pump intensity over the output range from 300-500 W cm-2. Ternary mixtures Xe:Ar:He were found to be the most promising. Total laser efficiency was found to be nearly the same for pumping the 2p8 or 2p9 state, reaching 61%-70% for a pump intensity of ~720 W cm-2 when the Xe fraction was in the range 0.001 ÷ 0.01 and Ar fraction—0.1 ÷ 0.5. However, when the 2p8 state was pumped, the maximum total efficiency occurred at larger pressures than for pumping of the 2p9 state. The discharge power density required to sustain a sufficient Xe* number density was in the range of tens of watts per cubic centimeter for 50% Ar in the mixture.

Modeling and simulation studies of human β3 adrenergic receptor and its interactions with agonists.

PubMed

Sahi, Shakti; Tewatia, Parul; Malik, Balwant K

2012-12-01

β3 adrenergic receptor (β3AR) is known to mediate various pharmacological and physiological effects such as thermogenesis in brown adipocytes, lipolysis in white adipocytes, glucose homeostasis and intestinal smooth muscle relaxation. Several efforts have been made in this field to understand their function and regulation in different human tissues and they have emerged as potential attractive targets in drug discovery for the treatment of diabetes, depression, obesity etc. Although the crystal structures of Bovine Rhodopsin and β2 adrenergic receptor have been resolved, to date there is no three dimensional structural information on β3AR. Our aim in this study was to model 3D structure of β3AR by various molecular modeling and simulation techniques. In this paper, we describe a refined predicted model of β3AR using different algorithms for structure prediction. The structural refinement and minimization of the generated 3D model of β3AR were done by Schrodinger suite 9.1. Docking studies of β3AR model with the known agonists enabled us to identify specific residues, viz, Asp 117, Ser 208, Ser 209, Ser 212, Arg 315, Asn 332, within the β3AR binding pocket, which might play an important role in ligand binding. Receptor ligand interaction studies clearly indicated that these five residues showed strong hydrogen bonding interactions with the ligands. The results have been correlated with the experimental data available. The predicted ligand binding interactions and the simulation studies validate the methods used to predict the 3D-structure.

Measurement of ion density in an atmospheric pressure argon with pin-to-plate dielectric barrier discharge by resonance of plasma radiation

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

Qi, Bing, E-mail: qibing@szu.edu.cn; Pan, Lizhu; Zhou, Qiujiao

2014-12-15

The measurements of the ion densities in the atmospheric AC barrier corona argon discharge are carried out by receiving and analyzing the frequencies of the electromagnetic radiation emitted from the plasma. An auxiliary excitation source composed of a pin-to-pin discharge system is introduced to excite the oscillations of the main discharge. To analyze the resonance mechanism, a complemented model based on a one-dimensional description of forced vibrations is given. Calculations indicate that Ar{sub 2}{sup +} is the dominant ion (∼89% in number density). By analyzing resonance frequencies, the ion densities of Ar{sub 2}{sup +} are in the order of 10{supmore » 19}∼10{sup 20}m{sup −3} and increase slowly as the applied voltage increases.« less

Measurement system to determine the total and angle-resolved light scattering of optical components in the deep-ultraviolet and vacuum-ultraviolet spectral regions

NASA Astrophysics Data System (ADS)

Schröder, Sven; Gliech, Stefan; Duparré, Angela

2005-10-01

An instrumentation for total and angle-resolved scattering (ARS) at 193 and 157 nm has been developed at the Fraunhofer Institute in Jena to meet the severe requirements for scattering analysis of deep- and vacuum-ultraviolet optical components. Extremely low backscattering levels of 10^-6 for the total scattering measurements and more than 9 orders of magnitude dynamic range for ARS have been accomplished. Examples of application extend from the control of at-wavelength scattering losses of superpolished substrates with rms roughness as small as 0.1 nm to the detection of volume material scattering and the study into the scattering of multilayer coatings. In addition, software programs were developed to model the roughness-induced light scattering of substrates and thin-film coatings.

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

NASA Technical Reports Server (NTRS)

Robinson, R. S.

1979-01-01

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

A mouse model of androgenetic alopecia.

PubMed

Crabtree, Judy S; Kilbourne, Edward J; Peano, Bryan J; Chippari, Susan; Kenney, Thomas; McNally, Christopher; Wang, Wei; Harris, Heather A; Winneker, Richard C; Nagpal, Sunil; Thompson, Catherine C

2010-05-01

Androgenetic alopecia (AGA), commonly known as male pattern baldness, is a form of hair loss that occurs in both males and females. Although the exact cause of AGA is not known, it is associated with genetic predisposition through traits related to androgen synthesis/metabolism and androgen signaling mediated by the androgen receptor (AR). Current therapies for AGA show limited efficacy and are often associated with undesirable side effects. A major hurdle to developing new therapies for AGA is the lack of small animal models to support drug discovery research. Here, we report the first rodent model of AGA. Previous work demonstrating that the interaction between androgen-bound AR and beta-catenin can inhibit Wnt signaling led us to test the hypothesis that expression of AR in hair follicle cells could interfere with hair growth in an androgen-dependent manner. Transgenic mice overexpressing human AR in the skin under control of the keratin 5 promoter were generated. Keratin 5-human AR transgenic mice exposed to high levels of 5alpha-dihydrotestosterone showed delayed hair regeneration, mimicking the AGA scalp. This effect is AR mediated, because treatment with the AR antagonist hydroxyflutamide inhibited the effect of dihydrotestosterone on hair growth. These results support the hypothesis that androgen-mediated hair loss is AR dependent and suggest that AR and beta-catenin mediate this effect. These mice can now be used to test new therapeutic agents for the treatment of AGA, accelerating the drug discovery process.

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

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

Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

PubMed

Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

2017-04-01

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

State space model approach for forecasting the use of electrical energy (a case study on: PT. PLN (Persero) district of Kroya)

NASA Astrophysics Data System (ADS)

Kurniati, Devi; Hoyyi, Abdul; Widiharih, Tatik

2018-05-01

Time series data is a series of data taken or measured based on observations at the same time interval. Time series data analysis is used to perform data analysis considering the effect of time. The purpose of time series analysis is to know the characteristics and patterns of a data and predict a data value in some future period based on data in the past. One of the forecasting methods used for time series data is the state space model. This study discusses the modeling and forecasting of electric energy consumption using the state space model for univariate data. The modeling stage is began with optimal Autoregressive (AR) order selection, determination of state vector through canonical correlation analysis, estimation of parameter, and forecasting. The result of this research shows that modeling of electric energy consumption using state space model of order 4 with Mean Absolute Percentage Error (MAPE) value 3.655%, so the model is very good forecasting category.

Detection and classification of subject-generated artifacts in EEG signals using autoregressive models.

PubMed

Lawhern, Vernon; Hairston, W David; McDowell, Kaleb; Westerfield, Marissa; Robbins, Kay

2012-07-15

We examine the problem of accurate detection and classification of artifacts in continuous EEG recordings. Manual identification of artifacts, by means of an expert or panel of experts, can be tedious, time-consuming and infeasible for large datasets. We use autoregressive (AR) models for feature extraction and characterization of EEG signals containing several kinds of subject-generated artifacts. AR model parameters are scale-invariant features that can be used to develop models of artifacts across a population. We use a support vector machine (SVM) classifier to discriminate among artifact conditions using the AR model parameters as features. Results indicate reliable classification among several different artifact conditions across subjects (approximately 94%). These results suggest that AR modeling can be a useful tool for discriminating among artifact signals both within and across individuals. Copyright © 2012 Elsevier B.V. All rights reserved.

RealityConvert: a tool for preparing 3D models of biochemical structures for augmented and virtual reality.

PubMed

Borrel, Alexandre; Fourches, Denis

2017-12-01

There is a growing interest for the broad use of Augmented Reality (AR) and Virtual Reality (VR) in the fields of bioinformatics and cheminformatics to visualize complex biological and chemical structures. AR and VR technologies allow for stunning and immersive experiences, offering untapped opportunities for both research and education purposes. However, preparing 3D models ready to use for AR and VR is time-consuming and requires a technical expertise that severely limits the development of new contents of potential interest for structural biologists, medicinal chemists, molecular modellers and teachers. Herein we present the RealityConvert software tool and associated website, which allow users to easily convert molecular objects to high quality 3D models directly compatible for AR and VR applications. For chemical structures, in addition to the 3D model generation, RealityConvert also generates image trackers, useful to universally call and anchor that particular 3D model when used in AR applications. The ultimate goal of RealityConvert is to facilitate and boost the development and accessibility of AR and VR contents for bioinformatics and cheminformatics applications. http://www.realityconvert.com. dfourch@ncsu.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

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

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

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

Holographic and light-field imaging for augmented reality

NASA Astrophysics Data System (ADS)

Lee, Byoungho; Hong, Jong-Young; Jang, Changwon; Jeong, Jinsoo; Lee, Chang-Kun

2017-02-01

We discuss on the recent state of the augmented reality (AR) display technology. In order to realize AR, various seethrough three-dimensional (3D) display techniques have been reported. We describe the AR display with 3D functionality such as light-field display and holography. See-through light-field display can be categorized by the optical elements which are used for see-through property: optical elements controlling path of the light-fields and those generating see-through light-field. Holographic display can be also a good candidate for AR display because it can reconstruct wavefront information and provide realistic virtual information. We introduce the see-through holographic display using various optical techniques.

CaMKII prevents spontaneous acrosomal exocytosis in sperm through induction of actin polymerization.

PubMed

Shabtay, Ortal; Breitbart, Haim

2016-07-01

In order to interact with the egg and undergo acrosomal exocytosis or the acrosome reaction (AR), mammalian spermatozoa must undergo a series of biochemical changes in the female reproductive tract, collectively called capacitation. We showed that F-actin is formed during sperm capacitation and fast depolymerization occurs prior to the AR. We hypothesized that F-actin protects the sperm from undergoing spontaneous-AR (sAR) which decreases fertilization rate. We show that activation of the actin-severing protein gelsolin induces a significant increase in sAR. Moreover, inhibition of CaMKII or PLD during sperm capacitation, caused an increase in sAR and inhibition of F-actin formation. Spermine, which leads to PLD activation, was able to reverse the effects of CaMKII inhibition on sAR-increase and F-actin-decrease. Furthermore, the increase in sAR and the decrease in F-actin caused by the inactivation of the PLD-pathway, were reversed by activation of CaMKII using H2O2 or by inhibiting protein phosphatase 1 which enhance the phosphorylation and oxidation states of CaMKII. These results indicate that two distinct pathways lead to F-actin formation in the sperm capacitation process which prevents the occurrence of sAR. Copyright © 2016 Elsevier Inc. All rights reserved.

Experimental study of NO2 reduction in N2/Ar and O2/Ar mixtures by pulsed corona discharge.

PubMed

Zhu, Xinbo; Zheng, Chenghang; Gao, Xiang; Shen, Xu; Wang, Zhihua; Luo, Zhongyang; Cen, Kefa

2014-11-01

Non-thermal plasma technology has been regarded as a promising alternative technology for NOx removal. The understanding of NO2 reduction characteristics is extremely important since NO2 reduction could lower the total NO oxidation rate in the plasma atmosphere. In this study, NO2 reduction was experimentally investigated using a non-thermal plasma reactor driven by a pulsed power supply for different simulated gas compositions and operating parameters. The NO2 reduction was promoted by increasing the specific energy density (SED), and the highest conversion rates were 33.7%, 42.1% and 25.7% for Ar, N2/Ar and O2/Ar, respectively. For a given SED, the NO2 conversion rate had the order N2/Ar>Ar>O2/Ar. The highest energy yield of 3.31g/kWh was obtained in N2/Ar plasma and decreased with increasing SED; the same trends were also found in the other two gas compositions. The conversion rate decreased with increasing initial NO2 concentration. Furthermore, the presence of N2 or O2 led to different reaction pathways for NO2 conversion due to the formation of different dominating reactive radicals. Copyright © 2014. Published by Elsevier B.V.

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.

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

Thermogravimetric kinetic study of agricultural residue biomass pyrolysis based on combined kinetics.

PubMed

Wang, Xun; Hu, Mian; Hu, Wanyong; Chen, Zhihua; Liu, Shiming; Hu, Zhiquan; Xiao, Bo

2016-11-01

Pyrolytic kinetic of an agricultural residue (AR) feedstock, a mixture of plants (cotton, wheat, rich, corn) stems, was investigated based on combined kinetics. The most suitable mechanism for AR one-step pyrolysis was f(α)=(1-α)(1.1816)α(-1.8428) with kinetic parameters of: apparent activation energy 221.7kJ/mol, pre-exponential factor 4.17E16s(-1). Pyrolysis of AR feedstock could not be described by one-step reaction attributes to heterogeneous features of pyrolysis processes. Combined kinetics three-parallel-reaction (CK-TPR) model fitted the pyrolysis experimental data very well. Reaction mechanisms for pseudo hemicelluloses, cellulose, lignin in CK-TPR model was f(α)=(1-α)(1.6244)α(-0.3371)[-ln(1-α)](-0.0515), f(α)=(1-α)(1.0597)α(-0.6909)[-ln(1-α)](0.9026) and f(α)=(1-α)(2.9577)α(-4.7719), respectively. Apparent activation energy of three pseudo components followed the order of Elignin(197.3kJ/mol)>Ecellulose(176.3kJ/mol)>Ehemicelluloses (151.1kJ/mol). Mechanism of hemicelluloses pyrolysis could be further expressed as f(α)=(1-α)(1.4). The pyrolytic mechanism of cellulose met the Nucleation well. However, mechanism of lignin pyrolysis was complex, which possibly was the combined effects of Nucleation, Diffusion, Geometrical contraction, and Power law. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

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

Global Analysis of Climate Change Projection Effects on Atmospheric Rivers

NASA Astrophysics Data System (ADS)

Espinoza, Vicky; Waliser, Duane E.; Guan, Bin; Lavers, David A.; Ralph, F. Martin

2018-05-01

A uniform, global approach is used to quantify how atmospheric rivers (ARs) change between Coupled Model Intercomparison Project Phase 5 historical simulations and future projections under the Representative Concentration Pathway (RCP) 4.5 and RCP8.5 warming scenarios. The projections indicate that while there will be 10% fewer ARs in the future, the ARs will be 25% longer, 25% wider, and exhibit stronger integrated water vapor transports (IVTs) under RCP8.5. These changes result in pronounced increases in the frequency (IVT strength) of AR conditions under RCP8.5: 50% (25%) globally, 50% (20%) in the northern midlatitudes, and 60% (20%) in the southern midlatitudes. The models exhibit systematic low biases across the midlatitudes in replicating historical AR frequency ( 10%), zonal IVT ( 15%), and meridional IVT ( 25%), with sizable intermodel differences. A more detailed examination of six regions strongly impacted by ARs suggests that the western United States, northwestern Europe, and southwestern South America exhibit considerable intermodel differences in projected changes in ARs.

A Projection of Changes in Landfilling Atmospheric River Frequency and Extreme Precipitation over Western North America from the Large Ensemble CESM Simulations

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

Hagos, Samson M.; Leung, Lai-Yung R.; Yoon, Jin-Ho

Simulations from the Community Earth System Model Large Ensemble project are analyzed to investigate the impact of global warming on atmospheric rivers (ARs). The model has notable biases in simulating the subtropical jet position and the relationship between extreme precipitation and moisture transport. After accounting for these biases, the model projects an ensemble mean increase of 35% in the number of landfalling AR days between the last twenty years of the 20th and 21st centuries. However, the number of AR associated extreme precipitation days increases only by 28% because the moisture transport required to produce extreme precipitation also increases withmore » warming. Internal variability introduces an uncertainty of ±8% and ±7% in the projected changes in AR days and associated extreme precipitation days. In contrast, accountings for model biases only change the projected changes by about 1%. The significantly larger mean changes compared to internal variability and to the effects of model biases highlight the robustness of AR responses to global warming.« less

Feldspar 40Ar/39Ar dating of ICDP PALEOVAN cores

NASA Astrophysics Data System (ADS)

Engelhardt, Jonathan Franz; Sudo, Masafumi; Stockhecke, Mona; Oberhänsli, Roland

2017-11-01

Volcaniclastic fall deposits in ICDP drilling cores from Lake Van, Turkey, contain sodium-rich sanidine and calcium-rich anorthoclase, which both comprise a variety of textural zoning and inclusions. An age model records the lake's history and is based on climate-stratigraphic correlations, tephrostratigraphy, paleomagnetics, and earlier 40Ar/39Ar analyses (Stockhecke et al., 2014b). Results from total fusion and stepwise heating 40Ar/39Ar analyses presented in this study allow for the comparison of radiometric constraints from texturally diversified feldspar and the multi-proxy lacustrine age model and vice versa. This study has investigated several grain-size fractions of feldspar from 13 volcaniclastic units. The feldspars show textural features that are visible in cathodoluminescence (CL) or back-scattered electron (BSE) images and can be subdivided into three dominant zoning-types: (1) compositional zoning, (2) round pseudo-oscillatory zoning and (3) resorbed and patchy zoning (Ginibre et al., 2004). Round pseudo-oscillatory zoning records a sensitive alternation of Fe and Ca that also reflects resorption processes. This is only visible in CL images. Compositional zoning reflects anticorrelated anorthite and orthoclase contents and is visible in BSE. Eleven inverse isochron ages from total fusion and three from stepwise heating analyses fit the age model. Four experiments resulted in older inverse isochron ages that do not concur with the model within 2σ uncertainties and that deviate from 1 ka to 17 ka minimum. C- and R-type zoning are interpreted as representing growth in magma chamber cupolas, as wall mushes, or in narrow conduits. Persistent compositions of PO-type crystals and abundant surfaces recording dissolution features correspond to formation within a magma chamber. C-type zoning and R-type zoning have revealed an irregular incorporation of melt and fluid inclusions. These two types of zoning in feldspar are interpreted as preferentially contributing either heterogeneously distributed excess 40Ar or inherited 40Ar to the deviating 40Ar/39Ar ages that are discussed in this study.

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

Radioactivities in returned lunar materials

NASA Technical Reports Server (NTRS)

1972-01-01

The Ar37, Ar39, and H3 were measured at four depths (from 0 to 19.5 cm) of the deep core from Apollo 16 and in four other Apollo 16 samples. The Ar37 increased steadily from 40 dpm/kg at the top of the core to 68 dpm/kg at 19-cm depth. The comparison of the Ar37 in the core with that in rock 15555 shows that the solar flare at the time of the Apollo 16 mission was approximately an order of magnitude less intense than solar flares of 24 January 1971 and 2 November 1969, which occurred before the Apollo 14 and 12 missions. The Ar39 activities in the top 19 cm of the deep core varied little with depth. Because the Apollo 16 samples have a much higher Ca content and much lower Fe and Ti contents than do the documented rocks from previous missions, the Ar39 in the Fe, Ca, and K can be determined from Ar39 measurements on lunar material if a Ti cross section is assumed.

A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.

PubMed

Ramasamy, Adaikalavan; Curjuric, Ivan; Coin, Lachlan J; Kumar, Ashish; McArdle, Wendy L; Imboden, Medea; Leynaert, Benedicte; Kogevinas, Manolis; Schmid-Grendelmeier, Peter; Pekkanen, Juha; Wjst, Matthias; Bircher, Andreas J; Sovio, Ulla; Rochat, Thierry; Hartikainen, Anna-Liisa; Balding, David J; Jarvelin, Marjo-Riitta; Probst-Hensch, Nicole; Strachan, David P; Jarvis, Deborah L

2011-11-01

Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

A Volterra series-based method for extracting target echoes in the seafloor mining environment.

PubMed

Zhao, Haiming; Ji, Yaqian; Hong, Yujiu; Hao, Qi; Ma, Liyong

2016-09-01

The purpose of this research was to evaluate the applicability of the Volterra adaptive method to predict the target echo of an ultrasonic signal in an underwater seafloor mining environment. There is growing interest in mining of seafloor minerals because they offer an alternative source of rare metals. Mining the minerals cause the seafloor sediments to be stirred up and suspended in sea water. In such an environment, the target signals used for seafloor mapping are unable to be detected because of the unavoidable presence of volume reverberation induced by the suspended sediments. The detection of target signals in reverberation is currently performed using a stochastic model (for example, the autoregressive (AR) model) based on the statistical characterisation of reverberation. However, we examined a new method of signal detection in volume reverberation based on the Volterra series by confirming that the reverberation is a chaotic signal and generated by a deterministic process. The advantage of this method over the stochastic model is that attributions of the specific physical process are considered in the signal detection problem. To test the Volterra series based method and its applicability to target signal detection in the volume reverberation environment derived from the seafloor mining process, we simulated the real-life conditions of seafloor mining in a water filled tank of dimensions of 5×3×1.8m. The bottom of the tank was covered with 10cm of an irregular sand layer under which 5cm of an irregular cobalt-rich crusts layer was placed. The bottom was interrogated by an acoustic wave generated as 16μs pulses of 500kHz frequency. This frequency is demonstrated to ensure a resolution on the order of one centimetre, which is adequate in exploration practice. Echo signals were collected with a data acquisition card (PCI 1714 UL, 12-bit). Detection of the target echo in these signals was performed by both the Volterra series based model and the AR model. The results obtained confirm that the Volterra series based method is more efficient in the detection of the signal in reverberation than the conventional AR model (the accuracy is 80% for the PIM-Volterra prediction model versus 40% for the AR model). Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Acceptance of Audience Response System by Corporations Using the Technology Acceptance Model

NASA Astrophysics Data System (ADS)

Chu, Hsing-Hui; Lu, Ta-Jung; Wann, Jong-Wen

The purpose of this research is to explore enterprises' acceptance of Audience Response System (ARS) using Technology Acceptance Model (TAM). The findings show that (1) IT characteristics and facilitating conditions could be external variables of TAM. (2) The degree of E-business has positive significant correlation with behavioral intention of employees. (3) TAM is a good model to predict and explain IT acceptance. (4) Demographic variables, industry and firm characteristics have no significant correlation with ARS acceptance. The results provide useful information to managers and ARS providers that (1) ARS providers should focus more on creating different usages to enhance interactivity and employees' using intention. (2) Managers should pay attention to build sound internal facilitating conditions for introducing IT. (3) According to the degree of E-business, managers should set up strategic stages of introducing IT. (4) Providers should increase product promotion and also leverage academic and government to promote ARS.

ARTutor--An Augmented Reality Platform for Interactive Distance Learning

ERIC Educational Resources Information Center

Lytridis, Chris; Tsinakos, Avgoustos; Kazanidis, Ioannis

2018-01-01

Augmented Reality (AR) has been used in various contexts in recent years in order to enhance user experiences in mobile and wearable devices. Various studies have shown the utility of AR, especially in the field of education, where it has been observed that learning results are improved. However, such applications require specialized teams of…

Mobile, real-time, and point-of-care augmented reality is robust, accurate, and feasible: a prospective pilot study.

PubMed

Kenngott, Hannes Götz; Preukschas, Anas Amin; Wagner, Martin; Nickel, Felix; Müller, Michael; Bellemann, Nadine; Stock, Christian; Fangerau, Markus; Radeleff, Boris; Kauczor, Hans-Ulrich; Meinzer, Hans-Peter; Maier-Hein, Lena; Müller-Stich, Beat Peter

2018-06-01

Augmented reality (AR) systems are currently being explored by a broad spectrum of industries, mainly for improving point-of-care access to data and images. Especially in surgery and especially for timely decisions in emergency cases, a fast and comprehensive access to images at the patient bedside is mandatory. Currently, imaging data are accessed at a distance from the patient both in time and space, i.e., at a specific workstation. Mobile technology and 3-dimensional (3D) visualization of radiological imaging data promise to overcome these restrictions by making bedside AR feasible. In this project, AR was realized in a surgical setting by fusing a 3D-representation of structures of interest with live camera images on a tablet computer using marker-based registration. The intent of this study was to focus on a thorough evaluation of AR. Feasibility, robustness, and accuracy were thus evaluated consecutively in a phantom model and a porcine model. Additionally feasibility was evaluated in one male volunteer. In the phantom model (n = 10), AR visualization was feasible in 84% of the visualization space with high accuracy (mean reprojection error ± standard deviation (SD): 2.8 ± 2.7 mm; 95th percentile = 6.7 mm). In a porcine model (n = 5), AR visualization was feasible in 79% with high accuracy (mean reprojection error ± SD: 3.5 ± 3.0 mm; 95th percentile = 9.5 mm). Furthermore, AR was successfully used and proved feasible within a male volunteer. Mobile, real-time, and point-of-care AR for clinical purposes proved feasible, robust, and accurate in the phantom, animal, and single-trial human model shown in this study. Consequently, AR following similar implementation proved robust and accurate enough to be evaluated in clinical trials assessing accuracy, robustness in clinical reality, as well as integration into the clinical workflow. If these further studies prove successful, AR might revolutionize data access at patient bedside.

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

Stability of Blowup for a 1D Model of Axisymmetric 3D Euler Equation

NASA Astrophysics Data System (ADS)

Do, Tam; Kiselev, Alexander; Xu, Xiaoqian

2016-10-01

The question of the global regularity versus finite- time blowup in solutions of the 3D incompressible Euler equation is a major open problem of modern applied analysis. In this paper, we study a class of one-dimensional models of the axisymmetric hyperbolic boundary blow-up scenario for the 3D Euler equation proposed by Hou and Luo (Multiscale Model Simul 12:1722-1776, 2014) based on extensive numerical simulations. These models generalize the 1D Hou-Luo model suggested in Hou and Luo Luo and Hou (2014), for which finite-time blowup has been established in Choi et al. (arXiv preprint. arXiv:1407.4776, 2014). The main new aspects of this work are twofold. First, we establish finite-time blowup for a model that is a closer approximation of the three-dimensional case than the original Hou-Luo model, in the sense that it contains relevant lower-order terms in the Biot-Savart law that have been discarded in Hou and Luo Choi et al. (2014). Secondly, we show that the blow-up mechanism is quite robust, by considering a broader family of models with the same main term as in the Hou-Luo model. Such blow-up stability result may be useful in further work on understanding the 3D hyperbolic blow-up scenario.

Computational prediction of the effects of the intra-aortic balloon pump on heart failure with valvular regurgitation using a 3D cardiac electromechanical model.

PubMed

Kim, Chang-Hyun; Song, Kwang-Soup; Trayanova, Natalia A; Lim, Ki Moo

2018-05-01

Intra-aortic balloon pump (IABP) is normally contraindicated in significant aortic regurgitation (AR). It causes and aggravates pre-existing AR while performing well in the event of mitral regurgitation (MR). Indirect parameters, such as the mean systolic pressure, product of heart rate and peak systolic pressure, and pressure-volume are used to quantify the effect of IABP on ventricular workload. However, to date, no studies have directly quantified the reduction in workload with IABP. The goal of this study is to examine the effect of IABP therapy on ventricular mechanics under valvular insufficiency by using a computational model of the heart. For this purpose, the 3D electromechanical model of the failing ventricles used in previous studies was coupled with a lumped parameter model of valvular regurgitation and the IABP-treated vascular system. The IABP therapy was disturbed in terms of reducing the myocardial tension generation and contractile ATP consumption by valvular regurgitation, particularly in the AR condition. The IABP worsened the problem of ventricular expansion induced as a result of the regurgitated blood volume during the diastole under the AR condition. The IABP reduced the LV stroke work in the AR, MR, and no regurgitation conditions. Therefore, the IABP helped the ventricle to pump blood and reduced the ventricular workload. In conclusion, the IABP partially performed its role in the MR condition. However, it was disturbed by the AR and worsened the cardiovascular responses that followed the AR. Therefore, this study computationally proved the reason for the clinical contraindication of IABP in AR patients.

A Modified LS+AR Model to Improve the Accuracy of the Short-term Polar Motion Prediction

NASA Astrophysics Data System (ADS)

Wang, Z. W.; Wang, Q. X.; Ding, Y. Q.; Zhang, J. J.; Liu, S. S.

2017-03-01

There are two problems of the LS (Least Squares)+AR (AutoRegressive) model in polar motion forecast: the inner residual value of LS fitting is reasonable, but the residual value of LS extrapolation is poor; and the LS fitting residual sequence is non-linear. It is unsuitable to establish an AR model for the residual sequence to be forecasted, based on the residual sequence before forecast epoch. In this paper, we make solution to those two problems with two steps. First, restrictions are added to the two endpoints of LS fitting data to fix them on the LS fitting curve. Therefore, the fitting values next to the two endpoints are very close to the observation values. Secondly, we select the interpolation residual sequence of an inward LS fitting curve, which has a similar variation trend as the LS extrapolation residual sequence, as the modeling object of AR for the residual forecast. Calculation examples show that this solution can effectively improve the short-term polar motion prediction accuracy by the LS+AR model. In addition, the comparison results of the forecast models of RLS (Robustified Least Squares)+AR, RLS+ARIMA (AutoRegressive Integrated Moving Average), and LS+ANN (Artificial Neural Network) confirm the feasibility and effectiveness of the solution for the polar motion forecast. The results, especially for the polar motion forecast in the 1-10 days, show that the forecast accuracy of the proposed model can reach the world level.

Annealing Effects on the Surface Plasmon of MgO Implanted with Gold

NASA Technical Reports Server (NTRS)

Ueda, A.; Mu, R.; Tung, Y. -S.; Henderson, D. O.; White, C. W.; Zuhr, R. A.; Zhu, Jane G.; Wang, P. W.

1997-01-01

Gold ion implantation was carried out with the energy of 1.1 MeV into (100) oriented MgO single crystal. Implanted doses are 1, 3, 6, 10 x 10(exp 16) ions/sq cm. The gold irradiation results in the formation of gold ion implanted layer with a thickness of 0.2 microns and defect formation. In order to form gold colloids from the as-implanted samples, we annealed the gold implanted MgO samples in three kinds of atmospheres: (1)Ar only, (2)H2 and Ar, and (3)O2 and Ar. The annealing over 1200 C enhanced the gold colloid formation which shows surface plasmon resonance band of gold. The surface plasmon bands of samples annealed in three kinds of atmospheres were found to be at 535 nm (Ar only), 524 nm(H2+Ar), and 560 nm (02+Ar), The band positions of surface plasmon can be reversibly changed by an additional annealing.

Effects of wintertime atmospheric river landfalls on surface air temperatures in the Western US: Analyses and model evaluation

NASA Astrophysics Data System (ADS)

Kim, J.; Guan, B.; Waliser, D. E.; Ferraro, R.

2016-12-01

Landfalling atmospheric rivers (ARs) affect the wintertime surface air temperatures as shown in earlier studies. The AR-related surface air temperatures can exert significant influence on the hydrology in the US Pacific coast region especially through rainfall-snowfall partitioning and the snowpack in high elevation watersheds as they are directly related with the freezing-level altitudes. These effects of temperature perturbations can in turn affect hydrologic events of various time scales such as flash flooding by the combined effects of rainfall and snowmelt, and the warm season runoff from melting snowpack, especially in conjunction with the AR effects on winter precipitation and rain-on-snow events in WUS. Thus, understanding the effects of AR landfalls on the surface temperatures and examining the capability of climate models in simulating these effects are an important practical concern for WUS. This study aims to understand the effects of AR landfalls on the characteristics of surface air temperatures in WUS, especially seasonal means and PDFs and to evaluate the fidelity of model data produced in the NASA downscaling experiment for the 10 winters from Nov. 1999 to Mar. 2010 using an AR-landfall chronology based on the vertically-integrated water vapor flux calculated from the MERRA2 reanalysis. Model skill is measured using metrics including regional means, a skill score based on correlations and mean-square errors, the similarity between two PDF shapes, and Taylor diagrams. Results show that the AR landfalls are related with higher surface air temperatures in WUS, especially in inland regions. The AR landfalls also reduce the range of surface air temperature PDF, largely by reducing the events in the lower temperature range. The shift in the surface air temperature PDF is consistent with the positive anomalies in the winter-mean temperature. Model data from the NASA downscaling experiment reproduce the AR effects on the temperature PDF, at least qualitatively; however, the skill in representing the spatial variations in the temperature anomalies is low. The skill of these model data also varies according to regions and the configuration of simulations. It was also found that the variations in model skill in simulating the spatial variability according to the model resolution is not systematic.

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.

Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors.

PubMed

Xu, K; Di Luca, D G; Orrú, M; Xu, Y; Chen, J-F; Schwarzschild, M A

2016-05-13

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. Copyright © 2016 IBRO. All rights reserved.

Bacillus sp. CDB3 isolated from cattle dip-sites possesses two ars gene clusters.

PubMed

Bhat, Somanath; Luo, Xi; Xu, Zhiqiang; Liu, Lixia; Zhang, Ren

2011-01-01

Contamination of soil and water by arsenic is a global problem. In Australia, the dipping of cattle in arsenic-containing solution to control cattle ticks in last centenary has left many sites heavily contaminated with arsenic and other toxicants. We had previously isolated five soil bacterial strains (CDB1-5) highly resistant to arsenic. To understand the resistance mechanism, molecular studies have been carried out. Two chromosome-encoded arsenic resistance (ars) gene clusters have been cloned from CDB3 (Bacillus sp.). They both function in Escherichia coli and cluster 1 exerts a much higher resistance to the toxic metalloid. Cluster 2 is smaller possessing four open reading frames (ORFs) arsRorf2BC, similar to that identified in Bacillus subtilis Skin element. Among the eight ORFs in cluster 1 five are analogs of common ars genes found in other bacteria, however, organized in a unique order arsRBCDA instead of arsRDABC. Three other putative genes are located directly downstream and designated as arsTIP based on the homologies of their theoretical translation sequences respectively to thioredoxin reductases, iron-sulphur cluster proteins and protein phosphatases. The latter two are novel of any known ars operons. The arsD gene from Bacillus species was cloned for the first time and the predict protein differs from the well studied E. coli ArsD by lacking two pairs of C-terminal cysteine residues. Its functional involvement in arsenic resistance has been confirmed by a deletion experiment. There exists also an inverted repeat in the intergenic region between arsC and arsD implying some unknown transcription regulation.

Inductively coupled Cl2/Ar plasma: Experimental investigation and modeling

NASA Astrophysics Data System (ADS)

Efremov, A. M.; Kim, Dong-Pyo; Kim, Chang-Il

2003-07-01

Electrophysical and kinetic characteristics of Cl2/Ar plasma were investigated to understand the influence of the addition of Ar on the volume densities and fluxes of active particles, both neutral and charged. Our analysis combined both experimental methods and plasma modeling. It was found that addition of Ar to Cl2 leads to deformation of the electron energy distribution function and an increase of the electron mean energy due to the ``transparency'' effect. Direct electron impact dissociation of Cl2 molecules represents the main source of chlorine atoms in the plasma volume. The contributions of stepwise dissociation and ionization involving Ar metastable atoms were found to be negligible. Addition of Ar to Cl2 causes the decrease of both electron and ion densities due to a decrease in the total ionization rate and the acceleration of heterogeneous decay of charged particles.

BAY 1024767 blocks androgen receptor mutants found in castration-resistant prostate cancer patients

PubMed Central

Sugawara, Tatsuo; Lejeune, Pascale; Köhr, Silke; Neuhaus, Roland; Faus, Hortensia; Gelato, Kathy A.; Busemann, Matthias; Cleve, Arwed; Lücking, Ulrich; von Nussbaum, Franz; Brands, Michael; Mumberg, Dominik; Jung, Klaus; Stephan, Carsten; Haendler, Bernard

2016-01-01

Androgen receptor (AR) mutations arise in patients developing resistance to hormone deprivation therapies. Here we describe BAY 1024767, a thiohydantoin derivative with strong antagonistic activity against nine AR variants with mutations located in the AR ligand-binding domain (LBD), and against wild-type AR. Antagonism was maintained, though reduced, at increased androgen levels. Anti-tumor efficacy was evidenced in vivo in the KuCaP-1 prostate cancer model which bears the W741C bicalutamide resistance mutation and in the syngeneic prostate cancer rat model Dunning R3327-G. The prevalence of six selected AR mutations was determined in plasma DNA originating from 100 resistant patients and found to be at least 12%. Altogether the results show BAY 1024767 to be a strong antagonist for several AR mutants linked to therapy resistance, which opens the door for next-generation compounds that can benefit patients based on their mutation profile. PMID:26760770

West Coast atmospheric river climatology in CMIP5 climate models

NASA Astrophysics Data System (ADS)

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

2015-12-01

In recent years, there has been a flurry of research on how atmospheric river events (ARs) will respond to anthropogenic global warming. This study uses 10 CMIP5 RCP 8.5 climate models to focus on changes in AR frequency, seasonality, and synoptic conditions along the west coast of the United States and is a follow-up to previous work by the same authors (Warner et al. 2015) which investigated expected changes in AR intensity in the same region. There are only very slight changes in annual AR climatology from the end of the last century to the end of this century when considering the most extreme integrated water vapor transport (IVT) events (99th percentile). However, when evaluating by the number of future days exceeding a historical threshold, there are significant increases in extreme IVT events in all months, especially during months when the majority of events take place. The peaks in historical and future frequency occur in similar months given the amount of model variability. Extreme IVT events appear to be occurring slightly earlier in the season, particularly along the northern US coast, and these results are similar to other studies. Spatially, 10-model mean historical composites of IVT reveal canonical AR conditions. At locations farther south, there is less model agreement on the spatial extent and intensity of AR events; whereas farther north, the various models are in agreement. Composites of future events indicate very little spatial change from historical events. The location and orientation of AR events in the historical and future time periods are similar, and the upper-level winds change little over that time period (Warner et al. 2015). This suggests little change in synoptic conditions for approaching ARs. The future-historical difference plots highlight the largest changes expected in the future, namely increases in IVT intensity which are primarily associated with thermodynamic changes related to future integrated water vapor increases due to a warming atmosphere.

Allergic rhinitis and inflammatory airway disease: interactions within the unified airspace.

PubMed

Marple, Bradley F

2010-01-01

Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.

Dynamic Granger-Geweke causality modeling with application to interictal spike propagation

PubMed Central

Lin, Fa-Hsuan; Hara, Keiko; Solo, Victor; Vangel, Mark; Belliveau, John W.; Stufflebeam, Steven M.; Hamalainen, Matti S.

2010-01-01

A persistent problem in developing plausible neurophysiological models of perception, cognition, and action is the difficulty of characterizing the interactions between different neural systems. Previous studies have approached this problem by estimating causal influences across brain areas activated during cognitive processing using Structural Equation Modeling and, more recently, with Granger-Geweke causality. While SEM is complicated by the need for a priori directional connectivity information, the temporal resolution of dynamic Granger-Geweke estimates is limited because the underlying autoregressive (AR) models assume stationarity over the period of analysis. We have developed a novel optimal method for obtaining data-driven directional causality estimates with high temporal resolution in both time and frequency domains. This is achieved by simultaneously optimizing the length of the analysis window and the chosen AR model order using the SURE criterion. Dynamic Granger-Geweke causality in time and frequency domains is subsequently calculated within a moving analysis window. We tested our algorithm by calculating the Granger-Geweke causality of epileptic spike propagation from the right frontal lobe to the left frontal lobe. The results quantitatively suggested the epileptic activity at the left frontal lobe was propagated from the right frontal lobe, in agreement with the clinical diagnosis. Our novel computational tool can be used to help elucidate complex directional interactions in the human brain. PMID:19378280

Measurement techniques for analysis of fission fragment excited gases

NASA Technical Reports Server (NTRS)

Schneider, R. T.; Carroll, E. E.; Davis, J. F.; Davie, R. N.; Maguire, T. C.; Shipman, R. G.

1976-01-01

Spectroscopic analysis of fission fragment excited He, Ar, Xe, N2, Ne, Ar-N2, and Ne-N2 have been conducted. Boltzmann plot analysis of He, Ar and Xe have indicated a nonequilibrium, recombining plasma, and population inversions have been found in these gases. The observed radiating species in helium have been adequately described by a simple kinetic model. A more extensive model for argon, nitrogen and Ar-N2 mixtures was developed which adequately describes the energy flow in the system and compares favorably with experimental measurements. The kinetic processes involved in these systems are discussed.

Dhofar 378 Martian shergottite: Evidence of early shock melting

NASA Astrophysics Data System (ADS)

Park, Jisun; Bogard, Donald D.; Mikouchi, Takashi; McKay, Gordon A.

2008-08-01

Shock heating of the Dhofar 378 (Dho 378) Martian shergottite produced melting, vesiculation, and flow of the plagioclase, which upon cooling recrystallized into complex textures. Heating experiments on the similar Zagami shergottite indicate that Dho 378 was shock heated to 1000-1100°C and was cooled at ~2.5°C/h. An 39Ar-40Ar analysis of Dho 378 plagioclase indicates different Ar diffusion domains and K/Ca ratios. The lower-temperature phase defines an Ar-Ar isochron age of 141 +/- 32 Ma. The higher-temperature phase released more 40Ar but does not define an age. The meteorite's thermal history was examined by constructing a generic model to compare cooling rates for objects of different sizes against fractional diffusion loss of Ar for different cooling times. Using gas diffusion parameter values measured for Dho 378, this model indicates that it is improbable that the major shock heating event occurred at the time that Dho 378 was ejected from Mars ~3 Ma ago. Rather, we suggest that the time of shock heating is probably given by its Ar-Ar age. For Dho 378 to cool sufficiently fast not to lose most of its 40Ar ~3 Ma ago would require it to have been ejected into space as an impossibly small object. Larger and more reasonable Mars ejection sizes indicate that Dho 378 should have lost most of its 40Ar. On the basis of plagioclase texture and Ar data, we suggest that a major impact event ~141 Ma ago melted Dho 378 plagioclase, degassed most of its 40Ar, and deposited it in crater ejecta to cool. A smaller and later impact ejected it into space ~3 Ma ago.

A natural laboratory for 40Ar/39Ar geochronology: ICDP cores from Lake Van, Turkey

NASA Astrophysics Data System (ADS)

Engelhardt, Jonathan; Sudo, Masafumi; Oberhänsli, Roland

2015-04-01

Pore water samples from ICDP Paleovan cores indicate a limited pore water exchange within Quaternary lake sediments. The core's volcaniclastic sections bear unaltered K-rich ternary feldspar and fresh to altered glass shards of predominantly rhyolitic composition. Whereas applying the 40Ar/39Ar method on feldspars resulted in ages timing a late-stage crystallization, glass shards had the potential to date the eruption. Volcanic glass is prone to modifications such as hydrous alteration (palagonitization) and devitrification (Cerling et al., 1985). These modifications affect the glass' chemistry and challenge the application of the 40Ar/39Ar method. Gaining precise radiometric ages from two phases has the potential to strengthen a climate-stratigraphic age-model (Stockhecke et al., 2014), and to significantly increase the temporal resolution on the deposition of the lake sediments. Vice versa the core's previous age model has the ability to question the reliability of 40Ar/39Ar eruption ages derived from ternary feldspars and glass shards. Multi- and single-grain total fusion on alkali feldspars from six volcaniclastic deposits resulted in Pleistocene ages that are in good agreement with the predicted age model. Feldspar phenocrysts from three ashes in the core's youngest section yielded consistent isochron ages that are significantly older than the model's prediction. Several distinct stratigraphic and paleomagnetic time markers of similar stratigraphic positions contradict to the older radiometric dates (Stockhecke et al., 2014). Partial resorption features of inherited feldspar domains and the involvement of excess 40Ar indicate incomplete degassing of older domains. To evaluate the magmatic history of the different domains EMPA mappings of trace elements that could be interpreted as Ar diffusion couples are currently conducted. Geochronology on Paleovan cores offers unique opportunities to monitor the effect of alteration on the Ar-systematics of volcanic glass shards and identifies a period of incorporation and incomplete degassing of inherited feldspar domains. References: Cerling, T.E., Brown, F.H., Bowman, J.R., 1985. Low-Temperature Alteration of Volcanic Glass - Hydration, Na, K, O-18 and Ar Mobility. Chemical Geology, 52 (3-4), 281-293. Stockhecke, M., Kwiecien, O., Vigliotti, L., Anselmetti, F., Beer, J., Çağatay, N. M., Channell, J. E. T., Kipfel, R., Lachner, J., Litt, T., Pickarski, N., Sturm, M., 2014. Chronostratigraphy of the 600,000 year old continental record of Lake Van (Turkey). Quarternary Science Reviews 104, 8-17

Binding properties of food colorant allura red with human serum albumin in vitro.

PubMed

Wang, Langhong; Zhang, Guowen; Wang, Yaping

2014-05-01

Allura red (AR) is a widely used colorant in food industry, but may have a potential security risk. In this study, the properties of interaction between AR and human serum albumin (HSA) in vitro were determined by fluorescence, UV-Vis absorption and circular dichroism (CD) spectroscopy combining with multivariate curve resolution-alternating least squares (MCR-ALS) chemometrics and molecular modeling approaches. An expanded UV-Vis data matrix was resolved by MCR-ALS method, and the concentration profiles and pure spectra for the three reaction components (AR, HSA, and AR-HSA complex) of the system were then successfully obtained to evaluate the progress interaction of AR with HSA. The calculated thermodynamic parameters indicated that hydrogen binding and hydrophobic interactions played major roles in the binding process, and the interaction induced a decrease in the protein surface hydrophobicity. The competitive experiments revealed that AR mainly located in Sudlow's site I of HSA, and this result was further supported by molecular modeling studies. Analysis of CD spectra found that the addition of AR induced the conformational changes of HSA. This study have provided new insight into the mechanism of interaction between AR and HSA.

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

PubMed Central

Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluís, Carme; Cortés, Antoni; Volkow, Nora D.; Schiffmann, Serge N.; Ferré, Sergi; Casadó, Vicent

2015-01-01

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain. PMID:26100888

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

PubMed

Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Cortés, Antoni; Volkow, Nora D; Schiffmann, Serge N; Ferré, Sergi; Casadó, Vicent

2015-07-07

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

PubMed

Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

2014-11-01

Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.

Aegeline inspired synthesis of novel β3-AR agonist improves insulin sensitivity in vitro and in vivo models of insulin resistance.

PubMed

Rajan, Sujith; Satish, Sabbu; Shankar, Kripa; Pandeti, Sukanya; Varshney, Salil; Srivastava, Ankita; Kumar, Durgesh; Gupta, Abhishek; Gupta, Sanchita; Choudhary, Rakhi; Balaramnavar, Vishal M; Narender, Tadigoppula; Gaikwad, Anil N

2018-03-07

In our drug discovery program of natural product, earlier we have reported Aegeline that is N-acylated-1-amino-2- alcohol, which was isolated from the leaves of Aeglemarmelos showed anti-hyperlipidemic activity for which the QSAR studies predicted the compound to be the β3-AR agonist, but the mechanism of its action was not elucidated. In our present study, we have evaluated the β3-AR activity of novel N-acyl-1-amino-3-arylopropanol synthetic mimics of aegeline and its beneficial effect in insulin resistance. In this study, we have proposed the novel pharmacophore model using reported molecules for antihyperlipidemic activity. The reported pharmacophore features were also compared with the newly developed pharmacophore model for the observed biological activity. Based on 3D pharmacophore modeling of known β3AR agonist, we screened 20 synthetic derivatives of Aegeline from the literature. From these, the top scoring compound 10C was used for further studies. The in-slico result was further validated in HEK293T cells co-trransfected with human β3-AR and CRE-Luciferase reporter plasmid for β3-AR activity.The most active compound was selected and β3-AR activity was further validated in white and brown adipocytes differentiated from human mesenchymal stem cells (hMSCs). Insulin resistance model developed in hMSC derived adipocytes was used to study the insulin sensitizing property. 8 week HFD fed C57BL6 mice was given 50 mg/Kg of the selected compound and metabolic phenotyping was done to evaluate its anti-diabetic effect. As predicted by in-silico 3D pharmacophore modeling, the compound 10C was found to be the most active and specific β3-AR agonist with EC 50 value of 447 nM. The compound 10C activated β3AR pathway, induced lipolysis, fatty acid oxidation and increased oxygen consumption rate (OCR) in human adipocytes. Compound 10C induced expression of brown adipocytes specific markers and reverted chronic insulin induced insulin resistance in white adipocytes. The compound 10C also improved insulin sensitivity and glucose tolerance in 8 week HFD fed C57BL6 mice. This study enlightens the use of in vitro insulin resistance model close to human physiology to elucidates the insulin sensitizing activity of the compound 10C and edifies the use of β3AR agonist as therapeutic interventions for insulin resistance and type 2 diabetes. Copyright © 2018. Published by Elsevier Inc.

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).

Limit on graviton mass from galaxy cluster Abell 1689

NASA Astrophysics Data System (ADS)

Desai, Shantanu

2018-02-01

To date, the only limit on graviton mass using galaxy clusters was obtained by Goldhaber and Nieto in 1974, using the fact that the orbits of galaxy clusters are bound and closed, and extend up to 580 kpc. From positing that only a Newtonian potential gives rise to such stable bound orbits, a limit on the graviton mass m_g<10^{-29} eV was obtained (PRD 9,1119, 1974). Recently, it has been shown that one can obtain closed bound orbits for Yukawa potential (arXiv:1705.02444), thus invalidating the main ansatz used in Goldhaber and Nieto to obtain the graviton mass bound. In order to obtain a revised estimate using galaxy clusters, we use dynamical mass models of the Abell 1689 (A1689) galaxy cluster to check their compatibility with a Yukawa gravitational potential. We assume mass models for the gas, dark matter, and galaxies for A1689 from arXiv:1703.10219 and arXiv:1610.01543, who used this cluster to test various alternate gravity theories, which dispense with the need for dark matter. We quantify the deviations in the acceleration profile using these mass models assuming a Yukawa potential and that obtained assuming a Newtonian potential by calculating the χ^2 residuals between the two profiles. Our estimated bound on the graviton mass (m_g) is thereby given by, m_g < 1.37 × 10^{-29} eV or in terms of the graviton Compton wavelength of, λ_g>9.1 × 10^{19} km at 90% confidence level.

Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer.

PubMed

Markowski, Mark C; Silberstein, John L; Eshleman, James R; Eisenberger, Mario A; Luo, Jun; Antonarakis, Emmanuel S

2017-01-01

A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice. In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC- (28%), CTC+/AR-V7- (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015). Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported thatmenwithAR-V7+results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

1. OVERALL VIEW TO NORTH, SHOWING BOMBER REVETMENT AR8 IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. OVERALL VIEW TO NORTH, SHOWING BOMBER REVETMENT AR-8 IN RELATION TO THE HANGARS OF MAIN BASE IN THE FAR DISTANCE, AND THE AIRPLANE FIREFIGHTING TRAINING MODEL (STRUCTURE NO. 273) AT FAR RIGHT. PURSUIT PLANE REVETMENT AR-9 IS DIRECTLY BEHIND AR-8, THROUGH HIDDEN FROM THIS ANGLE. (Panoramic view number 1 of 2 for AR-8). - Edwards Air Force Base, South Base, Rammed Earth Aircraft Dispersal Revetments, Western Shore of Rogers Dry Lake, Boron, Kern County, CA

Three-frequency BDS precise point positioning ambiguity resolution based on raw observables

NASA Astrophysics Data System (ADS)

Li, Pan; Zhang, Xiaohong; Ge, Maorong; Schuh, Harald

2018-02-01

All BeiDou navigation satellite system (BDS) satellites are transmitting signals on three frequencies, which brings new opportunity and challenges for high-accuracy precise point positioning (PPP) with ambiguity resolution (AR). This paper proposes an effective uncalibrated phase delay (UPD) estimation and AR strategy which is based on a raw PPP model. First, triple-frequency raw PPP models are developed. The observation model and stochastic model are designed and extended to accommodate the third frequency. Then, the UPD is parameterized in raw frequency form while estimating with the high-precision and low-noise integer linear combination of float ambiguity which are derived by ambiguity decorrelation. Third, with UPD corrected, the LAMBDA method is used for resolving full or partial ambiguities which can be fixed. This method can be easily and flexibly extended for dual-, triple- or even more frequency. To verify the effectiveness and performance of triple-frequency PPP AR, tests with real BDS data from 90 stations lasting for 21 days were performed in static mode. Data were processed with three strategies: BDS triple-frequency ambiguity-float PPP, BDS triple-frequency PPP with dual-frequency (B1/B2) and three-frequency AR, respectively. Numerous experiment results showed that compared with the ambiguity-float solution, the performance in terms of convergence time and positioning biases can be significantly improved by AR. Among three groups of solutions, the triple-frequency PPP AR achieved the best performance. Compared with dual-frequency AR, additional the third frequency could apparently improve the position estimations during the initialization phase and under constraint environments when the dual-frequency PPP AR is limited by few satellite numbers.

Augmenting the access grid using augmented reality

NASA Astrophysics Data System (ADS)

Li, Ying

2012-01-01

The Access Grid (AG) targets an advanced collaboration environment, with which multi-party group of people from remote sites can collaborate over high-performance networks. However, current AG still employs VIC (Video Conferencing Tool) to offer only pure video for remote communication, while most AG users expect to collaboratively refer and manipulate the 3D geometric models of grid services' results in live videos of AG session. Augmented Reality (AR) technique can overcome the deficiencies with its characteristics of combining virtual and real, real-time interaction and 3D registration, so it is necessary for AG to utilize AR to better assist the advanced collaboration environment. This paper introduces an effort to augment the AG by adding support for AR capability, which is encapsulated in the node service infrastructure, named as Augmented Reality Service (ARS). The ARS can merge the 3D geometric models of grid services' results and real video scene of AG into one AR environment, and provide the opportunity for distributed AG users to interactively and collaboratively participate in the AR environment with better experience.

Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.

PubMed

Hou, Xiyan; Majik, Mahesh S; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-Gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2012-01-12

Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)AR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

On the relative motions of long-lived Pacific mantle plumes.

PubMed

Konrad, Kevin; Koppers, Anthony A P; Steinberger, Bernhard; Finlayson, Valerie A; Konter, Jasper G; Jackson, Matthew G

2018-02-27

Mantle plumes upwelling beneath moving tectonic plates generate age-progressive chains of volcanos (hotspot chains) used to reconstruct plate motion. However, these hotspots appear to move relative to each other, implying that plumes are not laterally fixed. The lack of age constraints on long-lived, coeval hotspot chains hinders attempts to reconstruct plate motion and quantify relative plume motions. Here we provide 40 Ar/ 39 Ar ages for a newly identified long-lived mantle plume, which formed the Rurutu hotspot chain. By comparing the inter-hotspot distances between three Pacific hotspots, we show that Hawaii is unique in its strong, rapid southward motion from 60 to 50 Myrs ago, consistent with paleomagnetic observations. Conversely, the Rurutu and Louisville chains show little motion. Current geodynamic plume motion models can reproduce the first-order motions for these plumes, but only when each plume is rooted in the lowermost mantle.

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

Suppression of Tumor Growth and Muscle Wasting in a Transgenic Mouse Model of Pancreatic Cancer by the Novel Histone Deacetylase Inhibitor AR-42.

PubMed

Henderson, Sally E; Ding, Li-Yun; Mo, Xiaokui; Bekaii-Saab, Tanios; Kulp, Samuel K; Chen, Ching-Shih; Huang, Po-Hsien

2016-12-01

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. This study was aimed at evaluating the efficacy of AR-42 (formerly OSU-HDAC42), a novel histone deacetylase (HDAC) inhibitor currently in clinical trials, in suppressing tumor growth and/or cancer-induced muscle wasting in murine models of PDAC. The in vitro antiproliferative activity of AR-42 was evaluated in six human pancreatic cancer cell lines (AsPC-1, COLO-357, PANC-1, MiaPaCa-2, BxPC-3, SW1990). AsPC-1 subcutaneous xenograft and transgenic KP fl/fl C (LSL-Kras G12D ;Trp53 flox/flox ;Pdx-1-Cre) mouse models of pancreatic cancer were used to evaluate the in vivo efficacy of AR-42 in suppressing tumor growth and/or muscle wasting. Growth suppression in AR-42-treated cells was observed in all six human pancreatic cancer cell lines with dose-dependent modulation of proliferation and apoptotic markers, which was associated with the hallmark features of HDAC inhibition, including p21 upregulation and histone H3 hyperacetylation. Oral administration of AR-42 at 50 mg/kg every other day resulted in suppression of tumor burden in the AsPC-1 xenograft and KP fl/fl C models by 78% and 55%, respectively, at the end of treatment. Tumor suppression was associated with HDAC inhibition, increased apoptosis, and inhibition of proliferation. Additionally, AR-42 as a single agent preserved muscle size and increased grip strength in KP fl/fl C mice. Finally, the combination of AR-42 and gemcitabine in transgenic mice demonstrated a significant increase in survival than either agent alone. These results suggest that AR-42 represents a therapeutically promising strategy for the treatment of pancreatic cancer. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

AR(p) -based detrended fluctuation analysis

NASA Astrophysics Data System (ADS)

Alvarez-Ramirez, J.; Rodriguez, E.

2018-07-01

Autoregressive models are commonly used for modeling time-series from nature, economics and finance. This work explored simple autoregressive AR(p) models to remove long-term trends in detrended fluctuation analysis (DFA). Crude oil prices and bitcoin exchange rate were considered, with the former corresponding to a mature market and the latter to an emergent market. Results showed that AR(p) -based DFA performs similar to traditional DFA. However, the former DFA provides information on stability of long-term trends, which is valuable for understanding and quantifying the dynamics of complex time series from financial systems.

Interaction of the androgen receptor, ETV1 and PTEN pathways in mouse prostate varies with pathological stage and predicts cancer progression

PubMed Central

Higgins, Jake; Brogley, Michele; Palanisamy, Nallasivam; Mehra, Rohit; Ittmann, Michael M.; Li, Jun Z.; Tomlins, Scott A.; Robins, Diane M.

2015-01-01

To examine the impact of common somatic mutations in prostate cancer (PCa) on androgen receptor (AR) signaling, mouse models were designed to perturb sequentially the AR, ETV1 and PTEN pathways. Mice with "humanized" AR (hAR) alleles that modified AR transcriptional strength by varying polyglutamine tract (Q-tract) length were crossed with mice expressing a prostate-specific, AR-responsive ETV1 transgene (ETV1Tg). While hAR allele did not grossly affect ETV1-induced neoplasia, ETV1 strongly antagonized global AR regulation and repressed critical androgen-induced differentiation and tumor suppressor genes, such as Nkx3-1 and Hoxb13. When Pten was varied to determine its impact on disease progression, mice lacking one Pten allele (Pten+/−) developed more frequent prostatic intraepithelial neoplasia (PIN). Yet only those with the ETV1 transgene progressed to invasive adenocarcinoma. Furthermore, progression was more frequent with the short Q-tract (stronger) AR, suggesting that the AR, ETV1 and PTEN pathways cooperate in aggressive disease. On the Pten+/− background, ETV1 had markedly less effect on AR target genes. However, a strong inflammatory gene expression signature, notably upregulation of Cxcl16, was induced by ETV1. Comparison of mouse and human patient data stratified by presence of ETS fusion genes highlighted additional factors, some not previously associated with prostate cancer but for which targeted therapies are in development for other diseases. In sum, concerted use of these mouse models illuminates the complex interplay of AR, ETV1 and PTEN pathways in pre-cancerous neoplasia and early tumorigenesis, disease stages difficult to analyze in man. PMID:25631336

3D-Printed Broadband Dielectric Tube Terahertz Waveguide with Anti-Reflection Structure

NASA Astrophysics Data System (ADS)

Vogt, Dominik Walter; Leonhardt, Rainer

2016-11-01

We demonstrate broadband, low loss, and close-to-zero dispersion guidance of terahertz (THz) radiation in a dielectric tube with an anti-reflection structure (AR-tube waveguide) in the frequency range from 0.2 to 1.0 THz. The anti-reflection structure (ARS) consists of close-packed cones in a hexagonal lattice arranged on the outer surface of the tube cladding. The feature size of the ARS is in the order of the wavelength between 0.2 and 1.0 THz. The waveguides are fabricated with the versatile and cost efficient 3D-printing method. Terahertz time-domain spectroscopy (THz-TDS) measurements as well as 3D finite-difference time-domain simulations (FDTD) are performed to extensively characterize the AR-tube waveguides. Spectrograms, attenuation spectra, effective phase refractive indices, and the group-velocity dispersion parameters β 2 of the AR-tube waveguides are presented. Both the experimental and numerical results confirm the extended bandwidth and smaller group-velocity dispersion of the AR-tube waveguide compared to a low loss plain dielectric tube THz waveguide. The AR-tube waveguide prototypes show an attenuation spectrum close to the theoretical limit given by the infinite cladding tube waveguide.

Androgen receptor mitigates postoperative disease progression of hepatocellular carcinoma by suppressing CD90+ populations and cell migration and by promoting anoikis in circulating tumor cells

PubMed Central

Lai, Hsueh-Chou; Yeh, Chun-Chieh; Jeng, Long-Bin; Huang, Shang-Fen; Liao, Pei-Ying; Lei, Fu-Ju; Cheng, Wei-Chun; Hsu, Cheng-Lung; Cai, Xiujun; Chang, Chawnshang; Ma, Wen-Lung

2016-01-01

Purpose Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence. Experimental Design CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome. AR knockout was introduced in two mouse models of spontaneous HCC (carcinogen- and hepatitis B virus-related HCC) to delineate the role that AR plays in HCC recurrence. Biological systems analysis was used to investigate the cellular and molecular mechanisms. Results We found that the expression of AR in CTCs was negatively associated with HCC recurrence/progression after hepatectomy. Our results suggest that AR-mediated suppression of HCC recurrence/progression is governed by a three-pronged mechanism. First, AR suppresses the expression of CD90 in CTCs by upregulating Histone 3H2A. Second, AR suppresses cell migration at the transcriptome level. Third, AR promotes anoikis of CTCs via dysregulation of cytoskeletal adsorption. Conclusions The results indicate that AR expression may be the gatekeeper of postoperative HCC recurrence. Therefore, targeting AR in presurgical down-staging procedures may serve as a secondary prevention measure against HCC recurrence in the future. PMID:27340775

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.

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

Integrated Projectile Systems Synthesis Model (IPSSM)

DTIC Science & Technology

1976-08-01

Lethal area effectiveness Batch mode I terior ballistics Trajectory calculations Weapon system modeling ""TRACT (Cenetsmae an revers elds It ecesuy and...Ballistics (AR) 29 E. Terminal Effectiveness Calculations (LA) 31 F. 6-D Trajectory (TR) 32 G. Recoil Mechanism Design (RM) 33 H. Sabot Design (SD) 33 I...Exterior Ballistics Program (AR) 79 Key Variable Input D2 Exterior Ballistics Program (AR) 89 List of Tables E Terminal Effectiveness Program (LA) 93

A-Train Based Observational Metrics for Model Evaluation in Extratropical Cyclones

NASA Technical Reports Server (NTRS)

Naud, Catherine M.; Booth, James F.; Del Genio, Anthony D.; van den Heever, Susan C.; Posselt, Derek J.

2015-01-01

Extratropical cyclones contribute most of the precipitation in the midlatitudes, i.e. up to 70 during winter in the northern hemisphere, and can generate flooding, extreme winds, blizzards and have large socio-economic impacts. As such, it is important that general circulation models (GCMs) accurately represent these systems so their evolution in a warming climate can be understood. However, there are still uncertainties on whether warming will increase their frequency of occurrence, their intensity and how much rain or snow they bring. Part of the issue is that models have trouble representing their strength, but models also have biases in the amount of clouds and precipitation they produce. This is caused by potential issues in various aspects of the models: convection, boundary layer, and cloud scheme to only mention a few. In order to pinpoint which aspects of the models need improvement for a better representation of extratropical cyclone precipitation and cloudiness, we will present A-train based observational metrics: cyclone-centered, warm and cold frontal composites of cloud amount and type, precipitation rate and frequency of occurrence. Using the same method to extract similar fields from the model, we will present an evaluation of the GISS-ModelE2 and the IPSL-LMDZ-5B models, based on their AR5 and more recent versions. The AR5 version of the GISS model underestimates cloud cover in extratropical cyclones while the IPSL AR5 version overestimates it. In addition, we will show how the observed CloudSat-CALIPSO cloud vertical distribution across cold fronts changes with moisture amount and cyclone strength, and test if the two models successfully represent these changes. We will also show how CloudSat-CALIPSO derived cloud type (i.e. convective vs. stratiform) evolves across warm fronts as cyclones age, and again how this is represented in the models. Our third process-based analysis concerns cumulus clouds in the post-cold frontal region and how their amount relates to the stability of the boundary layer. This test uses Aqua cloud and vertical atmospheric profiles and when applied to the model output can help assess the accuracy of the convection, boundary layer and cloud scheme.

Moisture sources of the Atmospheric Rivers making landfall in western Europe

NASA Astrophysics Data System (ADS)

Trigo, Ricardo M.; Ramos, Alexandre M.; Nieto, Raquel; Tomé, Ricardo; Gimeno, Luis; Liberato, Margarida L. R.; Lavers, David A.

2017-04-01

An automated atmospheric river (AR) detection algorithm is used for the North Atlantic Ocean basin, allowing the identification of the major ARs affecting western European coasts between 1979 and 2012. The entire western coast of Europe was divided into five domains, namely the Iberian Peninsula (9.75W, 36-43.75N), France (4.5W, 43.75-50N), UK (4.5W, 50-59N), southern Scandinavia and the Netherlands (5.25E, 50-59N), and northern Scandinavia (5.25E, 59-70N). Following the identification of the main ARs that made landfall in western Europe, a Lagrangian analysis was then applied in order to identify the main areas where the moisture uptake was anomalous and contributed to the ARs reaching each domain. The Lagrangian data set used was obtained from the FLEXPART model global simulation from 1979 to 2012. The results show that, in general, for all regions considered, the major climatological areas for the anomalous moisture uptake extend along the subtropical North Atlantic, from the Florida Peninsula (northward of 20N) to each sink region, with the nearest coast to each sink region always appearing as a local maximum. In addition, during AR events the Atlantic subtropical source is reinforced and displaced, with a slight northward movement of the sources found when the sink region is positioned at higher latitudes. In conclusion, the results confirm not only the anomalous advection of moisture linked to ARs from subtropical ocean areas but also the existence of a tropical source, together with midlatitude anomaly sources at some locations closer to AR landfalls (Ramos et al., 2016). References: Ramos et al., (2016) Atmospheric rivers moisture sources from a Lagrangian perspective, Earth Syst. Dynam., 7, 371-384. Acknowledgements This work was supported by the project IMDROFLOOD - Improving Drought and Flood Early Warning, Forecasting and Mitigation using real-time hydroclimatic indicators (WaterJPI/0004/2014) funded by Fundação para a Ciência e a Tecnologia, Portugal (FCT). A. M. Ramos was supported by a FCT postdoctoral grant (FCT/DFRH/ SFRH/BPD/84328/2012). Raquel Nieto acknowledges the support of the Xunta de Galicia, Spain, through THIS (EM2014/043) project.

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Mobile augmented reality applications for heritage preservation in UNESCO world heritage sites through adopting the UTAUT model

NASA Astrophysics Data System (ADS)

Shang, Low Wei; Siang, Tan Gek; Zakaria, Mohd Hafiz bin; Emran, Muhammad Helmy

2017-04-01

Augmented reality (AR) technology has undergone enormous advancement and now AR applications can be seamlessly executed using modern-day smartphones. This study aims to develop a mobile AR application which consists of 3D AR models of historical monuments located within the UNESCO World Heritage Site in Melaka. The application allows tourists to obtain information of the monuments from the AR models, which provide an alternative way of visiting the actual monuments to prevent overcrowding effect and promote heritage preservation. Perceived Usefulness (PU), Perceived Ease of Use (PEU), Facilitating Conditions (FC), and Perceived Playfulness (PP) are proposed as the determinants of user's Behavioural Intention to Use (BI) the application. Using 50 tourists in Melaka as respondents, a pilot study has been conducted to determine user's acceptance of the AR mobile application based on the Unified Theory of Acceptance and Use of Technology (UTAUT). Cronbach's Alpha test validated the internal consistency of the measures. Multiple Linear Regression analysis suggested that the proposed determinants explained 51.2% in user's BI the application. PU was the strongest determinant followed by FC while PEU and PP were found to be insignificant.

The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety.

PubMed

Schramm, N L; McDonald, M P; Limbird, L E

2001-07-01

The noradrenergic system is involved in the regulation of many physiological and psychological processes, including the modulation of mood. The alpha(2)-adrenergic receptors (alpha(2)-ARs) modulate norepinephrine release, as well as the release of serotonin and other neurotransmitters, and are therefore potential targets for antidepressant and anxiolytic drug development. The current studies were undertaken to examine the role of the alpha(2A) subtype of alpha(2)-AR in mouse behavioral models of depression and anxiety. We have observed that the genetic knock-out of the alpha(2A)-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, alpha(2A)-AR knock-out mice appear more anxious than wild-type C57 Bl/6 mice in the rearing and light-dark models of anxiety after injection stress. These findings suggest that the alpha(2A)-AR may play a protective role in some forms of depression and anxiety and that the antidepressant effects of imipramine may be mediated by the alpha(2A)-AR.

Cimicifugamide from Cimicifuga rhizomes functions as a nonselective β-AR agonist for cardiac and sudorific effects.

PubMed

Wang, ZengYong; Wang, Qian; Zhang, Man; Hu, XueYan; Ding, GuoYu; Jiang, Min; Bai, Gang

2017-06-01

Cimicifuga rhizomes (CR) are used in the treatment of respiratory and cardiovascular diseases in traditional Chinese medicine, but their key effective components and mechanism of action have not yet been reported. In this study, the cardiac, antipyretic and sudorific effects of CR were evaluated using the toad heart failure in vitro model and mice fever and sweating in vivo models. Moreover, the UPLC/Q-TOF-MS-integrated β2-AR luciferase reporter gene assay system was used to screen the bioactive ingredients from CR extract, and the activity of this ingredient were verified using the above-mentioned in vitro and vivo models. Our results showed that CR had anti-heart failure, antipyretic and sweating effects, which could be antagonized by propranolol. On the other hand, cimicifugamide was screened as β2-AR agonist from CR and cimicifugamide could activate β1, 2-ARs more significantly than β3-AR in β-ARs selectivity assessment. The results not only revealed the key effective components and mechanism of CR in traditional use but also supplied a characteristic complementary ingredient for quality control of CR. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Update to the USDA-ARS fixed-wing spray nozzle models

USDA-ARS?s Scientific Manuscript database

The current USDA ARS Aerial Spray Nozzle Models were updated to reflect both new standardized measurement methods and systems, as well as, to increase operational spray pressure, aircraft airspeed and nozzle orientation angle limits. The new models were developed using both Central Composite Design...

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

40Ar/39Ar geochronology of terrestrial pyroxene

NASA Astrophysics Data System (ADS)

Ware, Bryant; Jourdan, Fred

2018-06-01

Geochronological techniques such as U/Pb in zircon and baddeleyite and 40Ar/39Ar on a vast range of minerals, including sanidine, plagioclase, and biotite, provide means to date an array of different geologic processes. Many of these minerals, however, are not always present in a given rock, or can be altered by secondary processes (e.g. plagioclase in mafic rocks) limiting our ability to derive an isotopic age. Pyroxene is a primary rock forming mineral for both mafic and ultramafic rocks and is resistant to alteration process but attempts to date this phase with 40Ar/39Ar has been met with little success so far. In this study, we analyzed pyroxene crystals from two different Large Igneous Provinces using a multi-collector noble gas mass spectrometer (ARGUS VI) since those machines have been shown to significantly improve analytical precision compared to the previous single-collector instruments. We obtain geologically meaningful and relatively precise 40Ar/39Ar plateau ages ranging from 184.6 ± 3.9 to 182.4 ± 0.8 Ma (2σ uncertainties of ±1.8-0.4%) and 506.3 ± 3.4 Ma for Tasmanian and Kalkarindji dolerites, respectively. Those data are indistinguishable from new and/or published U-Pb and 40Ar/39Ar plagioclase ages showing that 40Ar/39Ar dating of pyroxene is a suitable geochronological tool. Scrutinizing the analytical results of the pyroxene analyses as well as comparing them to the analytical result from plagioclase of the same samples indicate pure pyroxene was dated. Numerical models of argon diffusion in plagioclase and pyroxene support these observations. However, we found that the viability of 40Ar/39Ar dating approach of pyroxene can be affected by irradiation-induced recoil redistribution between thin pyroxene exsolution lamellae and the main pyroxene crystal, hence requiring careful petrographic observations before analysis. Finally, diffusion modeling show that 40Ar/39Ar of pyroxene can be used as a powerful tool to date the formation age of mafic rocks affected by greenschist metamorphism and will likely play an important role in high temperature thermochronology.

Stability Estimation of ABWR on the Basis of Noise Analysis

NASA Astrophysics Data System (ADS)

Furuya, Masahiro; Fukahori, Takanori; Mizokami, Shinya; Yokoya, Jun

In order to investigate the stability of a nuclear reactor core with an oxide mixture of uranium and plutonium (MOX) fuel installed, channel stability and regional stability tests were conducted with the SIRIUS-F facility. The SIRIUS-F facility was designed and constructed to provide a highly accurate simulation of thermal-hydraulic (channel) instabilities and coupled thermalhydraulics-neutronics instabilities of the Advanced Boiling Water Reactors (ABWRs). A real-time simulation was performed by modal point kinetics of reactor neutronics and fuel-rod thermal conduction on the basis of a measured void fraction in a reactor core section of the facility. A time series analysis was performed to calculate decay ratio and resonance frequency from a dominant pole of a transfer function by applying auto regressive (AR) methods to the time-series of the core inlet flow rate. Experiments were conducted with the SIRIUS-F facility, which simulates ABWR with MOX fuel installed. The variations in the decay ratio and resonance frequency among the five common AR methods are within 0.03 and 0.01 Hz, respectively. In this system, the appropriate decay ratio and resonance frequency can be estimated on the basis of the Yule-Walker method with the model order of 30.

Assessing the Integration of Audience Response System Technology in Teaching of Anatomical Sciences

PubMed Central

Alexander, Cara J.; Crescini, Weronika M.; Juskewitch, Justin E.; Lachman, Nirusha; Pawlina, Wojciech

2009-01-01

The goals of our study were to determine the predictive value and usability of an audience response system (ARS) as a knowledge assessment tool in an undergraduate medical curriculum. Over a three year period (2006–2008), data were collected from first year didactic blocks in Genetics/Histology and Anatomy/Radiology (n=42–50 per class). During each block, students answered clinically oriented multiple choice questions using the ARS. Students’ performances were recorded and cumulative ARS scores were compared with final examination performances. Correlation coefficients between these variables were calculated to assess the existence and direction of an association between ARS and final examination score. If associations existed, univariate models were then constructed using ARS as a predictor of final examination score. Student and faculty perception of ARS difficulty, usefulness, effect on performance, and preferred use were evaluated using a questionnaire. There was a statistically significant positive correlation between ARS and final examination scores in all didactic blocks and predictive univariate models were constructed for each relationship (all P < 0.0001). Students and faculty agreed that ARS was easy to use and are liable tool for providing real-time feedback that improved their performance and participation. In conclusion, we found ARS to be an effective assessment tool benefiting the faculty and the students in a curriculum focused on interaction and self-directed learning. PMID:19670428

Inhibition of Hippocampal β-Adrenergic Receptors Impairs Retrieval But Not Reconsolidation of Cocaine-Associated Memory and Prevents Subsequent Reinstatement

PubMed Central

Otis, James M; Fitzgerald, Michael K; Mueller, Devin

2014-01-01

Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment. PMID:23907403

Inhibition of hippocampal β-adrenergic receptors impairs retrieval but not reconsolidation of cocaine-associated memory and prevents subsequent reinstatement.

PubMed

Otis, James M; Fitzgerald, Michael K; Mueller, Devin

2014-01-01

Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment.

Assessing the integration of audience response system technology in teaching of anatomical sciences.

PubMed

Alexander, Cara J; Crescini, Weronika M; Juskewitch, Justin E; Lachman, Nirusha; Pawlina, Wojciech

2009-01-01

The goals of our study were to determine the predictive value and usability of an audience response system (ARS) as a knowledge assessment tool in an undergraduate medical curriculum. Over a three year period (2006-2008), data were collected from first year didactic blocks in Genetics/Histology and Anatomy/Radiology (n = 42-50 per class). During each block, students answered clinically oriented multiple choice questions using the ARS. Students' performances were recorded and cumulative ARS scores were compared with final examination performances. Correlation coefficients between these variables were calculated to assess the existence and direction of an association between ARS and final examination score. If associations existed, univariate models were then constructed using ARS as a predictor of final examination score. Student and faculty perception of ARS difficulty, usefulness, effect on performance, and preferred use were evaluated using a questionnaire. There was a statistically significant positive correlation between ARS and final examination scores in all didactic blocks and predictive univariate models were constructed for each relationship (all P < 0.0001). Students and faculty agreed that ARS was easy to use and a reliable tool for providing real-time feedback that improved their performance and participation. In conclusion, we found ARS to be an effective assessment tool benefiting the faculty and the students in a curriculum focused on interaction and self-directed learning. 2009 American Association of Anatomists

Active isotropic slabs: conditions for amplified reflection

NASA Astrophysics Data System (ADS)

Perez, Liliana I.; Matteo, Claudia L.; Etcheverry, Javier; Duplaá, María Celeste

2012-12-01

We analyse in detail the necessary conditions to obtain amplified reflection (AR) in isotropic interfaces when a plane wave propagates from a transparent medium towards an active one. First, we demonstrate analytically that AR is not possible if a single interface is involved. Then, we study the conditions for AR in a very simple configuration: normal incidence on an active slab immersed in transparent media. Finally, we develop an analysis in the complex plane in order to establish a geometrical method that not only describes the behaviour of active slabs but also helps to simplify the calculus.

Real time closed loop control of an Ar and Ar/O2 plasma in an ICP

NASA Astrophysics Data System (ADS)

Faulkner, R.; Soberón, F.; McCarter, A.; Gahan, D.; Karkari, S.; Milosavljevic, V.; Hayden, C.; Islyaikin, A.; Law, V. J.; Hopkins, M. B.; Keville, B.; Iordanov, P.; Doherty, S.; Ringwood, J. V.

2006-10-01

Real time closed loop control for plasma assisted semiconductor manufacturing has been the subject of academic research for over a decade. However, due to process complexity and the lack of suitable real time metrology, progress has been elusive and genuine real time, multi-input, multi-output (MIMO) control of a plasma assisted process has yet to be successfully implemented in an industrial setting. A Splasma parameter control strategy T is required to be adopted whereby process recipes which are defined in terms of plasma properties such as critical species densities as opposed to input variables such as rf power and gas flow rates may be transferable between different chamber types. While PIC simulations and multidimensional fluid models have contributed considerably to the basic understanding of plasmas and the design of process equipment, such models require a large amount of processing time and are hence unsuitable for testing control algorithms. In contrast, linear dynamical empirical models, obtained through system identification techniques are ideal in some respects for control design since their computational requirements are comparatively small and their structure facilitates the application of classical control design techniques. However, such models provide little process insight and are specific to an operating point of a particular machine. An ideal first principles-based, control-oriented model would exhibit the simplicity and computational requirements of an empirical model and, in addition, despite sacrificing first principles detail, capture enough of the essential physics and chemistry of the process in order to provide reasonably accurate qualitative predictions. This paper will discuss the development of such a first-principles based, control-oriented model of a laboratory inductively coupled plasma chamber. The model consists of a global model of the chemical kinetics coupled to an analytical model of power deposition. Dynamics of actuators including mass flow controllers and exhaust throttle are included and sensor characteristics are also modelled. The application of this control-oriented model to achieve multivariable closed loop control of specific species e.g. atomic Oxygen and ion density using the actuators rf power, Oxygen and Argon flow rates, and pressure/exhaust flow rate in an Ar/O2 ICP plasma will be presented.

The Viability and Value of Student- and Teacher-Created Augmented Reality Experiences

ERIC Educational Resources Information Center

O'Shea, Patrick; Curry-Corcoran, Daniel

2013-01-01

This paper describes the process and results of a project to incorporate Augmented Reality (AR) technologies and pedagogical approaches into a Virginian elementary school. The process involved training 5th grade teachers on the design and production of narrative-based AR games in order to give them the skills that they could then pass on to their…

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

PubMed Central

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

2010-01-01

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

High Spatial Resolution 40Ar/39Ar Geochronology of Lunar Impact Melt Rocks

NASA Astrophysics Data System (ADS)

Mercer, Cameron Mark

Impact cratering has played a key role in the evolution of the solid surfaces of Solar System bodies. While much of Earth’s impact record has been erased, its Moon preserves an extensive history of bombardment. Quantifying the timing of lunar impact events is crucial to understanding how impacts have shaped the evolution of early Earth, and provides the basis for estimating the ages of other cratered surfaces in the Solar System. Many lunar impact melt rocks are complex mixtures of glassy and crystalline “melt” materials and inherited clasts of pre-impact minerals and rocks. If analyzed in bulk, these samples can yield complicated incremental release 40Ar/39Ar spectra, making it challenging to uniquely interpret impact ages. Here, I have used a combination of high-spatial resolution 40Ar/39Ar geochronology and thermal-kinetic modeling to gain new insights into the impact histories recorded by such lunar samples. To compare my data to those of previous studies, I developed a software tool to account for differences in the decay, isotopic, and monitor age parameters used for different published 40Ar/39Ar datasets. Using an ultraviolet laser ablation microprobe (UVLAMP) system I selectively dated melt and clast components of impact melt rocks collected during the Apollo 16 and 17 missions. UVLAMP 40Ar/39Ar data for samples 77135, 60315, 61015, and 63355 show evidence of open-system behavior, and provide new insights into how to interpret some complexities of published incremental heating 40Ar/39Ar spectra. Samples 77115, 63525, 63549, and 65015 have relatively simple thermal histories, and UVLAMP 40Ar/39Ar data for the melt components of these rocks indicate the timing of impact events—spanning hundreds of millions of years—that influenced the Apollo 16 and 17 sites. My modeling and UVLAMP 40Ar/39Ar data for sample 73217 indicate that some impact melt rocks can quantitatively retain evidence for multiple melt-producing impact events, and imply that such polygenetic rocks should be regarded as high-value sampling opportunities during future exploration missions to cratered planetary surfaces. Collectively, my results complement previous incremental heating 40Ar/39Ar studies, and support interpretations that the Moon experienced a prolonged period of heavy bombardment early in its history.

Study of inelastic processes in Li+-Ar, K+-Ar, and Na+-He collisions in the energy range 0.5-10 keV

NASA Astrophysics Data System (ADS)

Lomsadze, Ramaz A.; Gochitashvili, Malkhaz R.; Kezerashvili, Roman Ya; Schulz, Michael

2017-11-01

Absolute cross sections are measured for charge-exchange, ionization, and excitation processes within the same experimental setup for the Li{}+-Ar, K{}+-Ar, and Na{}+-He collisions in the ion energy range of 0.5-10 keV. The results of the measurements and schematic correlation diagrams are used to analyze and determine the mechanisms for these processes. The experimental results show that the charge-exchange processes occur with high probabilities and electrons are predominantly captured in ground states. The contributions of various partial inelastic channels to the total ionization cross section are estimated, and a primary mechanism for the process is identified. In addition, the energy-loss spectrum is applied in order to estimate the relative contribution of different inelastic channels, and to determine the mechanisms for the ionization and for some excitation processes of Ar resonance lines for the {{{K}}}+-Ar collision system. The excitation cross sections for the helium and for the sodium doublet lines for the Na{}+-He collision system both reveal some unexpected features. A mechanism to explain this observation is suggested.

ArI/ArII laser induced fluorescence system for measurement of neutral and ion dynamics in a large scale helicon plasma

NASA Astrophysics Data System (ADS)

Kelly, R. F.; Meaney, K. D.; Gilmore, M.; Desjardins, T. R.; Zhang, Y.

2016-11-01

In order to investigate the role of both neutral and ion dynamics in large-scale helicon discharges, a laser induced fluorescence (LIF) system capable of measuring both ArI and ArII fluorescence using a single tunable laser is being developed. The system is based on a >250 mW solid state laser. For ArI measurements, the laser pumps the metastable (2P03/2)4s level to the (2P01/2)4p level using 696.7352 nm light, and fluorescence radiation from decay to the (2P01/2)4s level at 772.6333 nm is observed. For ArII, currently in development, the metastable (3P)3d 4F7/2 level will be pumped to the (3P)4p 4D07/2 level using 688.8511 nm, and decay fluorescence to the (3P)4s 4P5/2 level at 434.9285 nm measured. Here all wavelengths are in a vacuum.

ArI/ArII laser induced fluorescence system for measurement of neutral and ion dynamics in a large scale helicon plasma.

PubMed

Kelly, R F; Meaney, K D; Gilmore, M; Desjardins, T R; Zhang, Y

2016-11-01

In order to investigate the role of both neutral and ion dynamics in large-scale helicon discharges, a laser induced fluorescence (LIF) system capable of measuring both ArI and ArII fluorescence using a single tunable laser is being developed. The system is based on a >250 mW solid state laser. For ArI measurements, the laser pumps the metastable ( 2 P 0 3/2 )4s level to the ( 2 P 0 1/2 )4p level using 696.7352 nm light, and fluorescence radiation from decay to the ( 2 P 0 1/2 )4s level at 772.6333 nm is observed. For ArII, currently in development, the metastable ( 3 P)3d 4 F 7/2 level will be pumped to the ( 3 P)4p 4 D 0 7/2 level using 688.8511 nm, and decay fluorescence to the ( 3 P)4s 4 P 5/2 level at 434.9285 nm measured. Here all wavelengths are in a vacuum.

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

Measurements of population densities of metastable and resonant levels of argon using laser induced fluorescence

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

Nikolić, M.; Newton, J.; Sukenik, C. I.

2015-01-14

We present a new approach to measure population densities of Ar I metastable and resonant excited states in low temperature Ar plasmas at pressures higher than 1 Torr. This approach combines the time resolved laser induced fluorescence technique with the kinetic model of Ar. The kinetic model of Ar is based on calculating the population rates of metastable and resonant levels by including contributions from the processes that affect population densities of Ar I excited states. In particular, we included collisional quenching processes between atoms in the ground state and excited states, since we are investigating plasma at higher pressures. Wemore » also determined time resolved population densities of Ar I 2 p excited states by employing optical emission spectroscopy technique. Time resolved Ar I excited state populations are presented for the case of the post-discharge of the supersonic flowing microwave discharge at pressures of 1.7 and 2.3 Torr. The experimental set-up consists of a pulsed tunable dye laser operating in the near infrared region and a cylindrical resonance cavity operating in TE{sub 111} mode at 2.45 GHz. Results show that time resolved population densities of Ar I metastable and resonant states oscillate with twice the frequency of the discharge.« less

Initial assessment of the effects of energetic ion injections in the magnetosphere due to the transport of satellite power system components from low earth orbit to geosynchronous earth orbit

NASA Astrophysics Data System (ADS)

Curtis, S. A.; Grebowsky, J. M.

1980-07-01

Potentially serious environmental effects exist when cargo orbital transfer vehicle (COTV) ion propulsion is used on the scale proposed in the preliminary definition studies of the Satellite Power System. These effects of the large scale injections of ion propulsion exhaust in the plasmasphere and in the outer magnetosphere were shown to be highly model dependent with major differences existing in the predicted effects of two models, the ion cloud model and the ion sheath model. The expected total number density deposition of the propellant Ar(+) in the plasmasphere, the energy spectra of the deposited Ar(+) and time dependent behavior of the Ar(+) injected into the plasmasphere by a fleet of COTV vehicles differ drastically between the two models. The ion sheath model was demonstrated to be applicable to the proposed Ar(+) beam physics if the beam was divergent and turbulent whereas the ion cloud model was not a realistic approximation for such a beam because the "frozen-field" assumption on which it is based is not valid.

A design of energy detector for ArF excimer lasers

NASA Astrophysics Data System (ADS)

Feng, Zebin; Han, Xiaoquan; Zhou, Yi; Bai, Lujun

2017-08-01

ArF excimer lasers with short wavelength and high photon energy are widely applied in the field of integrated circuit lithography, material processing, laser medicine, and so on. Excimer laser single pulse energy is a very important parameter in the application. In order to detect the single pulse energy on-line, one energy detector based on photodiode was designed. The signal processing circuit connected to the photodiode was designed so that the signal obtained by the photodiode was amplified and the pulse width was broadened. The amplified signal was acquired by a data acquisition card and stored in the computer for subsequent data processing. The peak of the pulse signal is used to characterize the single pulse energy of ArF excimer laser. In every condition of deferent pulse energy value levels, a series of data about laser pulses energy were acquired synchronously using the Ophir energy meter and the energy detector. A data set about the relationship between laser pulse energy and the peak of the pulse signal was acquired. Then, by using the data acquired, a model characterizing the functional relationship between the energy value and the peak value of the pulse was trained based on an algorithm of machine learning, Support Vector Regression (SVR). By using the model, the energy value can be obtained directly from the energy detector designed in this project. The result shows that the relative error between the energy obtained by the energy detector and by the Ophir energy meter is less than 2%.

Classification and virtual screening of androgen receptor antagonists.

PubMed

Li, Jiazhong; Gramatica, Paola

2010-05-24

Computational tools, such as quantitative structure-activity relationship (QSAR), are highly useful as screening support for prioritization of substances of very high concern (SVHC). From the practical point of view, QSAR models should be effective to pick out more active rather than inactive compounds, expressed as sensitivity in classification works. This research investigates the classification of a big data set of endocrine-disrupting chemicals (EDCs)-androgen receptor (AR) antagonists, mainly aiming to improve the external sensitivity and to screen for potential AR binders. The kNN, lazy IB1, and ADTree methods and the consensus approach were used to build different models, which improve the sensitivity on external chemicals from 57.1% (literature) to 76.4%. Additionally, the models' predictive abilities were further validated on a blind collected data set (sensitivity: 85.7%). Then the proposed classifiers were used: (i) to distinguish a set of AR binders into antagonists and agonists; (ii) to screen a combined estrogen receptor binder database to find out possible chemicals that can bind to both AR and ER; and (iii) to virtually screen our in-house environmental chemical database. The in silico screening results suggest: (i) that some compounds can affect the normal endocrine system through a complex mechanism binding both to ER and AR; (ii) new EDCs, which are nonER binders, but can in silico bind to AR, are recognized; and (iii) about 20% of compounds in a big data set of environmental chemicals are predicted as new AR antagonists. The priority should be given to them to experimentally test the binding activities with AR.

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

PubMed Central

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

2015-01-01

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

Early Pleistocene 40Ar/39Ar ages for Bapang Formation hominins, Central Jawa, Indonesia

PubMed Central

Larick, Roy; Ciochon, Russell L.; Zaim, Yahdi; Sudijono; Suminto; Rizal, Yan; Aziz, Fachroel; Reagan, Mark; Heizler, Matthew

2001-01-01

The Sangiran dome is the primary stratigraphic window for the Plio-Pleistocene deposits of the Solo basin of Central Jawa. The dome has yielded nearly 80 Homo erectus fossils, around 50 of which have known findspots. With a hornblende 40Ar/39Ar plateau age of 1.66 ± 0.04 mega-annum (Ma) reportedly associated with two fossils [Swisher, C.C., III, Curtis, G. H., Jacob, T., Getty, A. G., Suprijo, A. & Widiasmoro (1994) Science 263, 1118–1121), the dome offers evidence that early Homo dispersed to East Asia during the earliest Pleistocene. Unfortunately, the hornblende pumice was sampled at Jokotingkir Hill, a central locality with complex lithostratigraphic deformation and dubious specimen provenance. To address the antiquity of Sangiran H. erectus more systematically, we investigate the sedimentary framework and hornblende 40Ar/39Ar age for volcanic deposits in the southeast quadrant of the dome. In this sector, Bapang (Kabuh) sediments have their largest exposure, least deformation, and most complete tephrostratigraphy. At five locations, we identify a sequence of sedimentary cycles in which H. erectus fossils are associated with epiclastic pumice. From sampled pumice, eight hornblende separates produced 40Ar/39Ar plateau ages ranging from 1.51 ± 0.08 Ma at the Bapang/Sangiran Formation contact, to 1.02 ± 0.06 Ma, at a point above the hominin-bearing sequence. The chronological sequence of 40Ar/39Ar ages follows stratigraphic order across the southeast quadrant. An intermediate level yielding four nearly complete crania has an age of about 1.25 Ma. PMID:11309488

Early Pleistocene 40Ar/39Ar ages for Bapang Formation hominins, Central Jawa, Indonesia.

PubMed

Larick, R; Ciochon, R L; Zaim, Y; Sudijono; Suminto; Rizal, Y; Aziz, F; Reagan, M; Heizler, M

2001-04-24

The Sangiran dome is the primary stratigraphic window for the Plio-Pleistocene deposits of the Solo basin of Central Jawa. The dome has yielded nearly 80 Homo erectus fossils, around 50 of which have known findspots. With a hornblende (40)Ar/(39)Ar plateau age of 1.66 +/- 0.04 mega-annum (Ma) reportedly associated with two fossils [Swisher, C.C., III, Curtis, G. H., Jacob, T., Getty, A. G., Suprijo, A. & Widiasmoro (1994) Science 263, 1118-1121), the dome offers evidence that early Homo dispersed to East Asia during the earliest Pleistocene. Unfortunately, the hornblende pumice was sampled at Jokotingkir Hill, a central locality with complex lithostratigraphic deformation and dubious specimen provenance. To address the antiquity of Sangiran H. erectus more systematically, we investigate the sedimentary framework and hornblende (40)Ar/(39)Ar age for volcanic deposits in the southeast quadrant of the dome. In this sector, Bapang (Kabuh) sediments have their largest exposure, least deformation, and most complete tephrostratigraphy. At five locations, we identify a sequence of sedimentary cycles in which H. erectus fossils are associated with epiclastic pumice. From sampled pumice, eight hornblende separates produced (40)Ar/(39)Ar plateau ages ranging from 1.51 +/- 0.08 Ma at the Bapang/Sangiran Formation contact, to 1.02 +/- 0.06 Ma, at a point above the hominin-bearing sequence. The chronological sequence of (40)Ar/(39)Ar ages follows stratigraphic order across the southeast quadrant. An intermediate level yielding four nearly complete crania has an age of about 1.25 Ma.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

PubMed

Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin

2010-04-01

Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

PubMed Central

2010-01-01

Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens. PMID:20359358

A complex Ar⋯Agsbnd I produced by laser ablation and characterised by rotational spectroscopy and ab initio calculations: Variation of properties along the series Ar⋯Agsbnd X (X = F, Cl, Br and I)

NASA Astrophysics Data System (ADS)

Medcraft, Chris; Mullaney, John C.; Walker, Nicholas R.; Legon, Anthony C.

2017-05-01

A complex of argon with silver iodide (Ar⋯Agsbnd I) has been formed in the gas phase by laser ablation of a silver iodide rod in the presence of a pulse of argon gas and its ground-state rotational spectrum has been detected by means of a chirped-pulse, F-T microwave instrument. Ar⋯Agsbnd I was characterised both by experimental properties determined from its rotational spectrum and by ab initio calculations carried out at the CCSD(T)(F12c)/cc-pVTZ-F12 explicitly correlated level of theory. The molecule was shown to be linear in the ground state, with atoms in the order shown. The Ar⋯Ag and Agsbnd I bond lengths r0(Ar⋯Ag) = 2.6759 Å and r0(Agsbnd I) = 2.5356 Å, the dissociation energy De = 16.7 kJ mol-1 for the process Ar⋯Agsbnd I = Ar + Agsbnd I, the intermolecular quadratic stretching force constant FAr⋯Ag = F22 = 20.2(8) N m-1 and the increase 0.033 in the ionicity ic of Agsbnd I when it enters the complex are reported. The opportunity has been taken to compare the way in which these properties vary along the series Ar⋯Agsbnd X (X = F, Cl, Br and I).

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

Evaluation of groundwater artificial recharge management scenario for sustainable water resources development in Gaza Strip

NASA Astrophysics Data System (ADS)

Rusteberg, Bernd; Azizur Rahman, M.; Abusaada, Muath; Rabi, Ayman; Rahman Tamimi, A.; Sauter, Martin

2010-05-01

The water resources in Gaza Strip are currently facing extreme over-exploitation which has led to a sharp decline of the groundwater level in this Mediterranean coastal aquifer overtime. Salinity of the groundwater is very high as a result of subsequent seawater intrusion of the aquifer. The contamination of the Gaza Strip groundwater by seawater has wide-ranging effects on the regional economy as well as agricultural productivity. In order to guarantee the sustainability of regional development, which requires the access to clean water, groundwater artificial recharge (AR) is being considered as a potential solution to this current water resources problem. The objective of the present study is to analyze several strategies for the implementation and management of AR in Gaza Strip and their potential impacts on agriculture, environment, and the socio-economy. Based on the water policy on wastewater reclamation and reuse (Yr. 2005 - 2025), six AR management strategies were developed in close cooperation with the local stakeholder community. These scenarios take into consideration the development of the new North Gaza Wastewater Treatment Plant and were also judged with respect to a base-line scenario, otherwise known as the "Do Nothing Approach." Multi-Criteria Decision Analysis (MCDA) on ranking of the AR management scenarios was used. Twenty-one criteria ranging over a wide spectrum and four categories (Environmental, Public Health, Social, and Economical) were defined to ensure sound evaluation of each of the six AR management scenarios. A detailed geo-database was prepared to analyze all the related spatial, non-spatial, and temporal data. Socio-economic studies, field surveys, mathematical modeling, and GIS analysis were used for the criteria quantification. In the MCDA, Analytical Hierarchy Method (AHP) combined with weighted Linear Combination (WLC) and Composite Programming (CP) was employed. The six AR management strategies were thus compared to the "Do Nothing Approach" based on the defined environmental, health, social, and economical criteria, the most important being related to the environment and the economy. The robustness of the achieved ranking of AR management options has been tested by changing the selected criteria, criteria importance and criteria structure. The final analysis shows that all six AR management strategies are better than "doing nothing". The implementation of groundwater artificial recharge with maximum possible infiltration of secondary treated effluent in conjunction with sustainable reuse of the recharged water for agricultural development is the most effective AR solution to the water resources problems of the Gaza Strip.

Quantitative fluid inclusion gas analysis of airburst, nuclear, impact and fulgurite glasses.

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

Parnell, John; Newsom, Horton E.; Blamey, Nigel J. F.

We present quantitative fluid inclusion gas analysis on a suite of violently-formed glasses. We used the incremental crush mass spectrometry method (Norman & Blamey, 2001) to analyze eight pieces of Libyan Desert Glass (LDG). As potential analogues we also analyzed trinitite, three impact crater glasses, and three fulgurites. The 'clear' LDG has the lowest CO{sub 2} content and O{sub 2}/Ar ratios are two orders of magnitude lower than atmospheric. The 'foamy' glass samples have heterogeneous CO{sub 2} contents and O{sub 2}/Ar ratios. N{sub 2}/Ar ratios are similar to atmospheric (83.6). H{sub 2} and He are elevated but it is difficultmore » to confirm whether they are of terrestrial or meteoritic origin. Combustion cannot account for oxygen depletion that matches the amount of CO{sub 2} produced. An alternative mechanism is required that removes oxygen without producing CO{sub 2}. Trinitite has exceedingly high CO{sub 2} which we attribute to carbonate breakdown of the caliche at ground zero. The O{sub 2}/Ar ratio for trinitite is lower than atmospheric but higher than all LDG samples. N{sub 2}/Ar ratios closely match atmospheric. Samples from Lonar, Henbury and Aouelloul impact craters have atmospheric N{sub 2}/Ar ratios. O{sub 2}/Ar ratios at Lonar and Henbury are 9.5 to 9.9 whereas the O{sub 2}/Ar ratio is 0.1 for the Aouelloul sample. In most fulgurites the N{sub 2}/Ar ratio is higher than atmospheric, possibly due to interference from CO. Oxygen ranges from 1.3 to 19.3%. Gas signatures of LDG inclusions neither match those from the craters, trinitite nor fulgurites. It is difficult to explain both the observed depletion of oxygen in the LDG and a CO{sub 2} level that is lower than it would be if the CO{sub 2} were simply a product of hydrocarbon combustion in air. One possible mechanism for oxygen depletion is that as air turbulently mixed with a hot jet of vaporized asteroid from an airburst and expanded, the atmospheric oxygen reacted with the metal vapor to form metal oxides that condensed. This observation is compatible with the model of Boslough & Crawford (2008) who suggest that an airburst incinerates organic materials over a large area, melting surface materials that then quench to form glass. Bubbles would contain a mixture of pre-existing atmosphere with combustion products from organic material and products of the reaction between vaporized cosmic materials (including metals) and terrestrial surface and atmosphere.« less

A Multiscale, Mechanism-Driven, Dynamic Model for the Effects of 5α-Reductase Inhibition on Prostate Maintenance

PubMed Central

Zager, Michael G.; Barton, Hugh A.

2012-01-01

A systems-level mathematical model is presented that describes the effects of inhibiting the enzyme 5α-reductase (5aR) on the ventral prostate of the adult male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is essential for androgen regulation in males, both in normal conditions and disease states. The hormone kinetics and downstream effects on reproductive organs associated with perturbing androgen regulation are complex and not necessarily intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the potent androgen 5α-dihydrotestosterone (DHT). This results in decreased cell proliferation, fluid production and 5aR expression as well as increased apoptosis in the ventral prostate. These regulatory changes collectively result in decreased prostate size and function, which can be beneficial to men suffering from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer. There are two distinct isoforms of 5aR in male humans and rats, and thus developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on the market for treatment of BPH, including finasteride and dutasteride. In this effort, comparisons of simulated vs. experimental T and DHT levels and prostate size are depicted, demonstrating the model accurately described an approximate 77% decrease in prostate size and nearly complete depletion of prostatic DHT following 21 days of daily finasteride dosing in rats. This implies T alone is not capable of maintaining a normal prostate size. Further model analysis suggests the possibility of alternative dosing strategies resulting in similar or greater effects on prostate size, due to complex kinetics between T, DHT and gene occupancy. With appropriate scaling and parameterization for humans, this model provides a multiscale modeling platform for drug discovery teams to test and generate hypotheses about drugging strategies for indications like BPH and prostate cancer, such as compound binding properties, dosing regimens, and target validation. PMID:22970204

77 FR 58802 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... 7 CFR 2.65, the Agricultural Research Service (ARS) needs to obtain certain basic information from the public. Online forms allow the public to request from ARS research data, models, materials, and publications as well as registration for scientific studies and events. Need and Use of the Information: ARS...

Determination of kojic acid based on the interface enhancement effects of carbon nanotube/alizarin red S modified electrode.

PubMed

Liu, Jieshu; Zhou, Dazhai; Liu, Xiaopeng; Wu, Kangbing; Wan, Chidan

2009-04-01

Based on non-covalent interactions such as pi-pi stacking, van der Waals interactions and strong adsorption, alizarin red S (ARS) interacts with multi-walled carbon nanotubes (MWNT), improving the solubility of MWNT in water and resulting in a stable MWNT/ARS solution. By successive cyclic sweeps between 0.0 and 2.2V in the MWNT/ARS solution, a MWNT/ARS composite film was fabricated on an electrode surface. The electrochemical behaviors of kojic acid at the bare electrode, the ARS film-modified electrode and the MWNT/ARS film-modified electrode were investigated. It was found that the oxidation signal of kojic acid significantly increased at the MWNT/ARS film-modified electrode, which was attributed to the unique properties of MWNT such as large surface area, strong adsorptive ability and subtle electronic character. The effects of pH and cyclic number of electropolymerization were examined. A rapid, sensitive and simple electrochemical method was then developed for the determination of kojic acid. This method exhibits good linearity over the range from 4.0 x 10(-7) to 6.0 x 10(-5)mol L(-1), and the limit of detection is as low as 1.0 x 10(-7)mol L(-1). In order to validate feasibility, the MWNT/ARS film-modified electrode was used for quantitative analysis of kojic acid in food samples.

A hybrid model of biased inductively coupled discharges1

NASA Astrophysics Data System (ADS)

Wen, Deqi; Lieberman, Michael A.; Zhang, Quanzhi; Liu, Yongxin; Wang, Younian

2016-09-01

A hybrid model, i.e. a global model coupled bidirectionally with a parallel Monte-Carlo collision (MCC) sheath model, is developed to investigate an inductively coupled discharge with a bias source. To validate this model, both bulk plasma density and ion energy distribution functions (IEDFs) are compared with experimental measurements in an argon discharge, and a good agreement is obtained. On this basis, the model is extended to weakly electronegative Ar/O2 plasma. The ion energy and angular distribution functions versus bias voltage amplitude are examined. The different ion species (Ar+, O2+,O+) have various behaviors because of the different masses. A low bias voltage, Ar+ has a single energy peak distribution and O+ has a bimodal distribution. At high bias voltage, the energy peak separation of O+ is wider than Ar+. 1This work has been supported by the National Nature Science Foundation of China (Grant No. 11335004) and Specific project (Grant No 2011X02403-001) and partially supported by Department of Energy Office of Fusion Energy Science Contract DE-SC000193 and a gift from the Lam Research Corporation.

Cooperative Dynamics of AR and ER Activity in Breast Cancer

PubMed Central

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

2016-01-01

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

Phonon-mediated nuclear spin relaxation in H2O

NASA Astrophysics Data System (ADS)

Yamakawa, Koichiro; Azami, Shinya; Arakawa, Ichiro

2017-03-01

A theoretical model of the phonon-mediated nuclear spin relaxation in H2O trapped by cryomatrices has been established for the first time. In order to test the validity of this model, we measured infrared spectra of H2O trapped in solid Ar, which showed absorption peaks due to rovibrational transitions of ortho- and para-H2O in the spectral region of the bending vibration. We monitored the time evolution of the spectra and analyzed the rotational relaxation associated with the nuclear spin flip to obtain the relaxation rates of H2O at temperatures of 5-15 K. Temperature dependence of the rate is discussed in terms of the devised model.

Membrane Driven Spatial Organization of GPCRs

NASA Astrophysics Data System (ADS)

Mondal, Sayan; Johnston, Jennifer M.; Wang, Hao; Khelashvili, George; Filizola, Marta; Weinstein, Harel

2013-10-01

Spatial organization of G-protein coupled receptors (GPCRs) into dimers and higher order oligomers has been demonstrated in vitro and in vivo. The pharmacological readout was shown to depend on the specific interfaces, but why particular regions of the GPCR structure are involved, and how ligand-determined states change them remains unknown. Here we show why protein-membrane hydrophobic matching is attained upon oligomerization at specific interfaces from an analysis of coarse-grained molecular dynamics simulations of the spontaneous diffusion-interaction of the prototypical beta2-adrenergic (β2AR) receptors in a POPC lipid bilayer. The energy penalty from mismatch is significantly reduced in the spontaneously emerging oligomeric arrays, making the spatial organization of the GPCRs dependent on the pattern of mismatch in the monomer. This mismatch pattern is very different for β2AR compared to the highly homologous and structurally similar β1AR, consonant with experimentally observed oligomerization patterns of β2AR and β1AR. The results provide a mechanistic understanding of the structural context of oligomerization.

Climatological Impact of Atmospheric River Based on NARCCAP and DRI-RCM Datasets

NASA Astrophysics Data System (ADS)

Mejia, J. F.; Perryman, N. M.

2012-12-01

This study evaluates spatial responses of extreme precipitation environments, typically associated with Atmospheric River events, using Regional Climate Model (RCM) output from NARCCAP dataset (50km grid size) and the Desert Research Institute-RCM simulations (36 and 12 km grid size). For this study, a pattern-detection algorithm was developed to characterize Atmospheric Rivers (ARs)-like features from climate models. Topological analysis of the enhanced elongated moisture flux (500-300hPa; daily means) cores is used to objectively characterize such AR features in two distinct groups: (i) zonal, north Pacific ARs, and (ii) subtropical ARs, also known as "Pineapple Express" events. We computed the climatological responses of the different RCMs upon these two AR groups, from which intricate differences among RCMs stand out. This study presents these climatological responses from historical and scenario driven simulations, as well as implications for precipitation extreme-value analyses.

Slow-proton reemission from noble-gas solids

NASA Astrophysics Data System (ADS)

Mills, A. P., Jr.; Leventhal, M.; Lanzerotti, M. Y.; Zuckerman, D. M.; Gullikson, E. M.; Brandes, G. R.

1990-10-01

A 1-μsec pulsed proton beam is being used to study H+ thermalization and reemission from solid target surfaces in ultrahigh vacuum in order to help clarify analogous experiments using muon beams. Using a solid Ar target, vapor deposited on an ~=6-K Cu substrate, the reemission probability Y is 6×10-4 at a proton implantation energy E+H=1.4 keV and falls with increasing energy to 3×10-4 at E+H=5 keV and 2×10-4 at E+H=15 keV. Ne exhibits a 25% larger yield, while the yield for Kr is a factor of 4 lower. The reemitted protons are slow, with kinetic energies of order 1 eV. The reemitted proton yield Y decreases with an ~=100-m time constant, presumably due to deposition of neutral contaminants associated with the incoming beam, and thus ruling out the possibility that the slow protons originate from surface contaminants. For Ar, the observed variation of Y with E+H is interpreted with the help of a Monte Carlo calculation of the stopping and backscattering of the incident protons. The observed magnitude of Y is significantly greater than the calculated backscattering yield at the higher values of E+H. We therefore hypothesize that few-eV protons in the solid, which are considered ``stopped'' by the simulation, can diffuse a significant distance and escape into the vacuum. In our model, the diffusion length for few-eV protons in pristine solid Ar, λ0, is found to be λ0=(50+70-20) Å. However, the diffusion length we deduce from our measurements and simulations varies with E+H, possibly because of the interaction of the slow proton with its implantation trail. The vacancy density is computed to be too low for few-eV protons near the surface to be trapped at defects created by the energetic incoming particle. On the other hand, the proton neutralization probability could be dependent on the availability of free electrons in the ion trail of the implanted particle [O. E. Mogensen, J. Chem. Phys. 60, 998 (1974)]. Extension of our model to the case of positive muons suggests that an experiment to moderate 4-MeV μ+ with a solid Ar target [Harshman et al., Phys. Rev. B 36, 8850 (1987)] may have underestimated λ0 for μ+ due to sample impurities. It appears that the prospects for making a slow μ+ beam are better than we thought, but that remoderation of a few-keV μ+ beam using an Ar surface might have an efficiency less than 1% due to the high muonium-formation probability.

Particle-in-cell/Monte Carlo collisions treatment of an Ar/O2 magnetron discharge used for the reactive sputter deposition of TiOx films

NASA Astrophysics Data System (ADS)

Bultinck, E.; Bogaerts, A.

2009-10-01

The physical processes in an Ar/O2 magnetron discharge used for the reactive sputter deposition of TiOx thin films were simulated with a 2d3v particle-in-cell/Monte Carlo collisions (PIC/MCC) model. The plasma species taken into account are electrons, Ar+ ions, fast Arf atoms, metastable Arm* atoms, Ti+ ions, Ti atoms, O+ ions, O2+ ions, O- ions and O atoms. This model accounts for plasma-target interactions, such as secondary electron emission and target sputtering, and the effects of target poisoning. Furthermore, the deposition process is described by an analytical surface model. The influence of the O2/Ar gas ratio on the plasma potential and on the species densities and fluxes is investigated. Among others, it is shown that a higher O2 pressure causes the region of positive plasma potential and the O- density to be more spread, and the latter to decrease. On the other hand, the deposition rates of Ti and O are not much affected by the O2/Ar proportion. Indeed, the predicted stoichiometry of the deposited TiOx film approaches x=2 for nearly all the investigated O2/Ar proportions.

Flow Structure and Force Variation with Aspect Ratio for a Two-Degree-of-Freedom Flapping Wing

NASA Astrophysics Data System (ADS)

Burge, Matthew; Favale, James; Ringuette, Matthew

2014-11-01

We investigate experimentally the effect of aspect ratio (AR) on the flow structure and forces of a two-degree-of-freedom flapping wing. Flapping wings are known to produce complex and unsteady vortex loop structures, and the objective is to characterize their variation with AR and how this influences the lift force. Previous results on rotating wings demonstrated that changes in AR significantly affect the three-dimensional flow structure and lift coefficient. This is primarily due to the relatively greater influence of the tip vortex for lower AR. At Reynolds number of order O(103) we test wings of AR = 2-4, values typically found in nature, with simplified planform shapes. The lift force is measured using a submersible transducer at the base of the wing in a glycerin-water mixture. The qualitative, three-dimensional vortex loop structure for different ARs is obtained using multi-color dye flow visualization. Guided by this, quantitative three-component flow information, namely vorticity, the Q-criterion, and circulation, is acquired from stereoscopic particle image velocimetry in key planes. Of interest is how these parameters and the vortex loop topology vary with AR, and their connection to features in the unsteady force signal. This work is supported by the National Science Foundation, Award Number 1336548, supervised by Dr. Dimitrios Papavassiliou.

Role of beta1-adrenoceptor in the basolateral amygdala of rats with anxiety-like behavior.

PubMed

Fu, Ailing; Li, Xiaorong; Zhao, Baoquan

2008-05-23

There are evidence suggesting that the function of adrenergic receptor is affected in the amygdala of animals with anxiety-like behavior. However, beta-adrenoceptor (beta-AR) subtypes, consisting of three subtypes, exert different effects on anxiety regulation. In order to determine the function of the beta1-AR subtype in anxiety-like behavior, we investigated the change of beta1-AR expression by immunostaining in the basolateral amygdala (BLA) of rats treated by conditional fear training. The results indicated that the level of beta1-AR was significantly increased in the BLA of fear-conditioned animals as compared that of controls. In animal behavioral tests, animals treated with selective beta1-AR antagonist metoprolol before conditional fear training exhibited a significant attenuation of anxiety-like behavior characterized by increased percentage of time spent and percentage of entries in the open arms, and increased number of head-dips in the elevated plus-maze (EPM) test compared with the animals treated with only saline. Furthermore, the rats pretreated with metoprolol in the conditional fear training significantly decreased the freezing behavior in the test compared with the controls. The results suggested that the beta1-AR played an important role in anxiety-like behavior, and inhibition of the beta1-AR in the BLA could produce anxiolytic effect.

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis

PubMed Central

Tosetti, Valentina; Sassone, Jenny; Ferri, Anna L. M.; Taiana, Michela; Bedini, Gloria; Nava, Sara; Brenna, Greta; Di Resta, Chiara; Pareyson, Davide; Di Giulio, Anna Maria; Carelli, Stephana

2017-01-01

The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE), and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT. PMID:28704421

Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis.

PubMed

Tosetti, Valentina; Sassone, Jenny; Ferri, Anna L M; Taiana, Michela; Bedini, Gloria; Nava, Sara; Brenna, Greta; Di Resta, Chiara; Pareyson, Davide; Di Giulio, Anna Maria; Carelli, Stephana; Parati, Eugenio A; Gorio, Alfredo

2017-01-01

The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE), and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.

Augmented reality-guided artery-first pancreatico-duodenectomy.

PubMed

Marzano, Ettore; Piardi, Tullio; Soler, Luc; Diana, Michele; Mutter, Didier; Marescaux, Jacques; Pessaux, Patrick

2013-11-01

Augmented Reality (AR) in surgery consists in the fusion of synthetic computer-generated images (3D virtual model) obtained from medical imaging preoperative work-up and real-time patient images with the aim to visualize unapparent anatomical details. The potential of AR navigation as a tool to improve safety of the surgical dissection is presented in a case of pancreatico-duodenectomy (PD). A 77-year-old male patient underwent an AR-assisted PD. The 3D virtual anatomical model was obtained from thoraco-abdominal CT scan using customary software (VR-RENDER®, IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM®, Karl Storz, Tüttlingen, Germany) as well as different visible landmarks (inferior vena cava, left renal vein, aorta, superior mesenteric vein, inferior margin of the pancreas). A computer scientist manually registered virtual and real images using a video mixer (MX 70; Panasonic, Secaucus, NJ) in real time. Dissection of the superior mesenteric artery and the hanging maneuver were performed under AR guidance along the hanging plane. AR allowed for precise and safe recognition of all the important vascular structures. Operative time was 360 min. AR display and fine registration was performed within 6 min. The postoperative course was uneventful. The pathology was positive for ampullary adenocarcinoma; the final stage was pT1N0 (0/43 retrieved lymph nodes) with clear surgical margins. AR is a valuable navigation tool that can enhance the ability to achieve a safe surgical resection during PD.

Evaluation of Visual Acuity Measurements after Autorefraction versus Manual Refraction in Eyes with and without Diabetic Macular Edema

PubMed Central

Sun, Jennifer K.; Qin, Haijing; Aiello, Lloyd Paul; Melia, Michele; Beck, Roy W.; Andreoli, Christopher M.; Edwards, Paul A.; Glassman, Adam R.; Pavlica, Michael R.

2012-01-01

Objective To compare visual acuity (VA) scores after autorefraction versus research protocol manual refraction in eyes of patients with diabetes and a wide range of VA. Methods Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) VA Test© letter score (EVA) was measured after autorefraction (AR-EVA) and after Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction (MR-EVA). Testing order was randomized, study participants and VA examiners were masked to refraction source, and a second EVA utilizing an identical manual refraction (MR-EVAsupl) was performed to determine test-retest variability. Results In 878 eyes of 456 study participants, median MR-EVA was 74 (Snellen equivalent approximately 20/32). Spherical equivalent was often similar for manual and autorefraction (median difference: 0.00, 5th and 95th percentiles −1.75 to +1.13 Diopters). However, on average, MR-EVA results were slightly better than AR-EVA results across the entire VA range. Furthermore, variability between AR-EVA and MR-EVA was substantially greater than the test-retest variability of MR-EVA (P<0.001). Variability of differences was highly dependent on autorefractor model. Conclusions Across a wide range of VA at multiple sites using a variety of autorefractors, VA measurements tend to be worse with autorefraction than manual refraction. Differences between individual autorefractor models were identified. However, even among autorefractor models comparing most favorably to manual refraction, VA variability between autorefraction and manual refraction is higher than the test-retest variability of manual refraction. The results suggest that with current instruments, autorefraction is not an acceptable substitute for manual refraction for most clinical trials with primary outcomes dependent on best-corrected VA. PMID:22159173

Atmospheric River Frequency and Intensity Changes in CMIP5 Climate Model Projections

NASA Astrophysics Data System (ADS)

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

2012-12-01

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 currently unclear how these events will change in frequency and intensity as a result of climate change in the coming century. While climate model global mean precipitation match observations reasonably well in historical runs, precipitation frequency and intensity is generally poorly represented at local scales; however, synoptic-scale features are more realistically simulated by climate models, and AR events can be identified by extremely high values of integrated water vapor flux at points near the West Coast. There have been many recent studies indicating changes in synoptic-scale features under climate change that could have meaningful impacts on the frequency and intensity of ARs. In this study, a suite of CMIP5 models are used to analyze predicted changes in frequency and intensity of AR events impacting the West Coast from the contemporary period (1970-1999) to the end of this century (2070-2099). Generally, integrated water vapor is predicted to increase in these models (both the mean and extremes) while low-level wind decreases and upper-level wind increases. This study aims to determine the influence of these changes on precipitation intensity in AR events in future climate simulations.

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.

Use of argon to measure gas exchange in turbulent mountain streams

NASA Astrophysics Data System (ADS)

Hall, Robert O., Jr.; Madinger, Hilary L.

2018-05-01

Gas exchange is a parameter needed in stream metabolism and trace gas emissions models. One way to estimate gas exchange is via measuring the decline of added tracer gases such as sulfur hexafluoride (SF6). Estimates of oxygen (O2) gas exchange derived from SF6 additions require scaling via Schmidt number (Sc) ratio, but this scaling is uncertain under conditions of high gas exchange via bubbles because scaling depends on gas solubility as well as Sc. Because argon (Ar) and O2 have nearly identical Schmidt numbers and solubility, Ar may be a useful tracer gas for estimating stream O2 exchange. Here we compared rates of gas exchange measured via Ar and SF6 for turbulent mountain streams in Wyoming, USA. We measured Ar as the ratio of Ar : N2 using a membrane inlet mass spectrometer (MIMS). Normalizing to N2 confers higher precision than simply measuring [Ar] alone. We consistently enriched streams with Ar from 1 to 18 % of ambient Ar concentration and could estimate gas exchange rate using an exponential decline model. The mean ratio of gas exchange of Ar relative to SF6 was 1.8 (credible interval 1.1 to 2.5) compared to the theoretical estimate 1.35, showing that using SF6 would have underestimated exchange of Ar. Steep streams (slopes 11-12 %) had high rates of gas exchange velocity normalized to Sc = 600 (k600, 57-210 m d-1), and slope strongly predicted variation in k600 among all streams. We suggest that Ar is a useful tracer because it is easily measured, requires no scaling assumptions to estimate rates of O2 exchange, and is not an intense greenhouse gas as is SF6. We caution that scaling from rates of either Ar or SF6 gas exchange to CO2 is uncertain due to solubility effects in conditions of bubble-mediated gas transfer.

Modeling and Optimization of GEDIT for In Situ Contaminant Destruction in the Vadose Zone

DTIC Science & Technology

2012-04-01

010.7264E+01 AP 8AP 9 10.4817E-010.5290E-010.7264E+01 AQ 8AQ 9 10.4817E-010.5290E-010.7264E+01 AR 8AR 9...010.1000E+010.3207E+001. AP 8AQ 8 30.1000E+010.1000E+010.3207E+001. AQ 8AR 8 30.1000E+010.1000E+010.3207E+001. AR

Automation and Robotics for Human Mars Exploration (AROMA)

NASA Technical Reports Server (NTRS)

Hofmann, Peter; von Richter, Andreas

2003-01-01

Automation and Robotics (A&R) systems are a key technology for Mars exploration. All over the world initiatives in this field aim at developing new A&R systems and technologies for planetary surface exploration. From December 2000 to February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA (Automation and Robotics for Human Mars Exploration) under ESA contract in order to define a reference architecture of A&R elements in support of a human Mars exploration program. One of the goals of this effort is to initiate new developments and to maintain the competitiveness of European industry within this field. c2003 Published by Elsevier Science Ltd.

Automation and Robotics for Human Mars Exploration (AROMA).

PubMed

Hofmann, Peter; von Richter, Andreas

2003-01-01

Automation and Robotics (A&R) systems are a key technology for Mars exploration. All over the world initiatives in this field aim at developing new A&R systems and technologies for planetary surface exploration. From December 2000 to February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA (Automation and Robotics for Human Mars Exploration) under ESA contract in order to define a reference architecture of A&R elements in support of a human Mars exploration program. One of the goals of this effort is to initiate new developments and to maintain the competitiveness of European industry within this field. c2003 Published by Elsevier Science Ltd.

Climate change, atmospheric rivers, and floods in California - a multimodel analysis of storm frequency and magnitude changes

USGS Publications Warehouse

Dettinger, M.

2011-01-01

Recent studies have documented the important role that "atmospheric rivers" (ARs) of concentrated near-surface water vapor above the Pacific Ocean play in the storms and floods in California, Oregon, and Washington. By delivering large masses of warm, moist air (sometimes directly from the Tropics), ARs establish conditions for the kinds of high snowlines and copious orographic rainfall that have caused the largest historical storms. In many California rivers, essentially all major historical floods have been associated with AR storms. As an example of the kinds of storm changes that may influence future flood frequencies, the occurrence of such storms in historical observations and in a 7-model ensemble of historical-climate and projected future climate simulations is evaluated. Under an A2 greenhouse-gas emissions scenario (with emissions accelerating throughout the 21st Century), average AR statistics do not change much in most climate models; however, extremes change notably. Years with many AR episodes increase, ARs with higher-than-historical water-vapor transport rates increase, and AR storm-temperatures increase. Furthermore, the peak season within which most ARs occur is commonly projected to lengthen, extending the flood-hazard season. All of these tendencies could increase opportunities for both more frequent and more severe floods in California under projected climate changes. ?? 2011 American Water Resources Association.

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

PubMed

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

2017-01-29

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

Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA.

PubMed

Zboray, Lori; Pluciennik, Anna; Curtis, Dana; Liu, Yuhong; Berman-Booty, Lisa D; Orr, Christopher; Kesler, Cristina T; Berger, Tamar; Gioeli, Daniel; Paschal, Bryce M; Merry, Diane E

2015-12-15

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by a polyglutamine expansion in the androgen receptor (AR) and is associated with misfolding and aggregation of the mutant AR. We investigated the role of an interdomain interaction between the amino (N)-terminal FxxLF motif and carboxyl (C)-terminal AF-2 domain in a mouse model of SBMA. Male transgenic mice expressing polyQ-expanded AR with a mutation in the FxxLF motif (F23A) to prevent the N/C interaction displayed substantially improved motor function compared with N/C-intact AR-expressing mice and showed reduced pathological features of SBMA. Serine 16 phosphorylation was substantially enhanced by the F23A mutation; moreover, the protective effect of AR F23A was dependent on this phosphorylation. These results reveal an important role for the N/C interaction on disease onset in mice and suggest that targeting AR conformation could be a therapeutic strategy for patients with SBMA. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Gas Chromatography Data Classification Based on Complex Coefficients of an Autoregressive Model

DOE PAGES

Zhao, Weixiang; Morgan, Joshua T.; Davis, Cristina E.

2008-01-01

This paper introduces autoregressive (AR) modeling as a novel method to classify outputs from gas chromatography (GC). The inverse Fourier transformation was applied to the original sensor data, and then an AR model was applied to transform data to generate AR model complex coefficients. This series of coefficients effectively contains a compressed version of all of the information in the original GC signal output. We applied this method to chromatograms resulting from proliferating bacteria species grown in culture. Three types of neural networks were used to classify the AR coefficients: backward propagating neural network (BPNN), radial basis function-principal component analysismore » (RBF-PCA) approach, and radial basis function-partial least squares regression (RBF-PLSR) approach. This exploratory study demonstrates the feasibility of using complex root coefficient patterns to distinguish various classes of experimental data, such as those from the different bacteria species. This cognition approach also proved to be robust and potentially useful for freeing us from time alignment of GC signals.« less

Prediction of muscle performance during dynamic repetitive movement

NASA Technical Reports Server (NTRS)

Byerly, D. L.; Byerly, K. A.; Sognier, M. A.; Squires, W. G.

2003-01-01

BACKGROUND: During long-duration spaceflight, astronauts experience progressive muscle atrophy and often perform strenuous extravehicular activities. Post-flight, there is a lengthy recovery period with an increased risk for injury. Currently, there is a critical need for an enabling tool to optimize muscle performance and to minimize the risk of injury to astronauts while on-orbit and during post-flight recovery. Consequently, these studies were performed to develop a method to address this need. METHODS: Eight test subjects performed a repetitive dynamic exercise to failure at 65% of their upper torso weight using a Lordex spinal machine. Surface electromyography (SEMG) data was collected from the erector spinae back muscle. The SEMG data was evaluated using a 5th order autoregressive (AR) model and linear regression analysis. RESULTS: The best predictor found was an AR parameter, the mean average magnitude of AR poles, with r = 0.75 and p = 0.03. This parameter can predict performance to failure as early as the second repetition of the exercise. CONCLUSION: A method for predicting human muscle performance early during dynamic repetitive exercise was developed. The capability to predict performance to failure has many potential applications to the space program including evaluating countermeasure effectiveness on-orbit, optimizing post-flight recovery, and potential future real-time monitoring capability during extravehicular activity.

Application of Optical Diagnosis to Aged Low-Voltage Cable Insulation in Nuclear Plants

NASA Astrophysics Data System (ADS)

Katagiri, Junichi; Takezawa, Yoshitaka; Shouji, Hiroshi

We have developed a novel non-destructive optical diagnosis technique for low-voltage cable insulations used in nuclear power plants. The key features of this diagnosis are the use of two wavelengths to measure the change in reflective absorbance (ΔAR), the use of polarized light to measure crystallinity and the use of element volatilizing to measure fluorescence. Chemical kinetics is used to predict the lifetimes of the cable insulations. When cable insulations darken and harden by time degradation, the ΔAR and depolarization parameters increase. This means that the cross-linking density in the cable insulations increases due to deterioration reactions. When the cross-linking density of insulation increases, its elasticity, corresponding to the material's life, increases. Similarly, as the crystallinity increases due to the change in the high-order structure of the insulating resin caused by irradiation, its elongation property decreases. The elongation property of insulation is one of the most important parameters that can be used to evaluate material lifetimes, because it relates to elasticity. The ΔAR correlated with the elongation property, and the correlation coefficient of an accelerated experiment using model pieces was over 0.9. Thus, we concluded that this optical diagnosis should be applied to evaluate the degradation of cable insulations used in nuclear power plants.

Implicit–explicit (IMEX) Runge–Kutta methods for non-hydrostatic atmospheric models

DOE PAGES

Gardner, David J.; Guerra, Jorge E.; Hamon, François P.; ...

2018-04-17

The efficient simulation of non-hydrostatic atmospheric dynamics requires time integration methods capable of overcoming the explicit stability constraints on time step size arising from acoustic waves. In this work, we investigate various implicit–explicit (IMEX) additive Runge–Kutta (ARK) methods for evolving acoustic waves implicitly to enable larger time step sizes in a global non-hydrostatic atmospheric model. The IMEX formulations considered include horizontally explicit – vertically implicit (HEVI) approaches as well as splittings that treat some horizontal dynamics implicitly. In each case, the impact of solving nonlinear systems in each implicit ARK stage in a linearly implicit fashion is also explored.The accuracymore » and efficiency of the IMEX splittings, ARK methods, and solver options are evaluated on a gravity wave and baroclinic wave test case. HEVI splittings that treat some vertical dynamics explicitly do not show a benefit in solution quality or run time over the most implicit HEVI formulation. While splittings that implicitly evolve some horizontal dynamics increase the maximum stable step size of a method, the gains are insufficient to overcome the additional cost of solving a globally coupled system. Solving implicit stage systems in a linearly implicit manner limits the solver cost but this is offset by a reduction in step size to achieve the desired accuracy for some methods. Overall, the third-order ARS343 and ARK324 methods performed the best, followed by the second-order ARS232 and ARK232 methods.« less

Implicit-explicit (IMEX) Runge-Kutta methods for non-hydrostatic atmospheric models

NASA Astrophysics Data System (ADS)

Gardner, David J.; Guerra, Jorge E.; Hamon, François P.; Reynolds, Daniel R.; Ullrich, Paul A.; Woodward, Carol S.

2018-04-01

The efficient simulation of non-hydrostatic atmospheric dynamics requires time integration methods capable of overcoming the explicit stability constraints on time step size arising from acoustic waves. In this work, we investigate various implicit-explicit (IMEX) additive Runge-Kutta (ARK) methods for evolving acoustic waves implicitly to enable larger time step sizes in a global non-hydrostatic atmospheric model. The IMEX formulations considered include horizontally explicit - vertically implicit (HEVI) approaches as well as splittings that treat some horizontal dynamics implicitly. In each case, the impact of solving nonlinear systems in each implicit ARK stage in a linearly implicit fashion is also explored. The accuracy and efficiency of the IMEX splittings, ARK methods, and solver options are evaluated on a gravity wave and baroclinic wave test case. HEVI splittings that treat some vertical dynamics explicitly do not show a benefit in solution quality or run time over the most implicit HEVI formulation. While splittings that implicitly evolve some horizontal dynamics increase the maximum stable step size of a method, the gains are insufficient to overcome the additional cost of solving a globally coupled system. Solving implicit stage systems in a linearly implicit manner limits the solver cost but this is offset by a reduction in step size to achieve the desired accuracy for some methods. Overall, the third-order ARS343 and ARK324 methods performed the best, followed by the second-order ARS232 and ARK232 methods.

Implicit–explicit (IMEX) Runge–Kutta methods for non-hydrostatic atmospheric models

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

Gardner, David J.; Guerra, Jorge E.; Hamon, François P.

The efficient simulation of non-hydrostatic atmospheric dynamics requires time integration methods capable of overcoming the explicit stability constraints on time step size arising from acoustic waves. In this work, we investigate various implicit–explicit (IMEX) additive Runge–Kutta (ARK) methods for evolving acoustic waves implicitly to enable larger time step sizes in a global non-hydrostatic atmospheric model. The IMEX formulations considered include horizontally explicit – vertically implicit (HEVI) approaches as well as splittings that treat some horizontal dynamics implicitly. In each case, the impact of solving nonlinear systems in each implicit ARK stage in a linearly implicit fashion is also explored.The accuracymore » and efficiency of the IMEX splittings, ARK methods, and solver options are evaluated on a gravity wave and baroclinic wave test case. HEVI splittings that treat some vertical dynamics explicitly do not show a benefit in solution quality or run time over the most implicit HEVI formulation. While splittings that implicitly evolve some horizontal dynamics increase the maximum stable step size of a method, the gains are insufficient to overcome the additional cost of solving a globally coupled system. Solving implicit stage systems in a linearly implicit manner limits the solver cost but this is offset by a reduction in step size to achieve the desired accuracy for some methods. Overall, the third-order ARS343 and ARK324 methods performed the best, followed by the second-order ARS232 and ARK232 methods.« less

A Quaternary Geomagnetic Instability Time Scale

NASA Astrophysics Data System (ADS)

Singer, B. S.

2013-12-01

Reversals and excursions of Earth's geomagnetic field create marker horizons that are readily detected in sedimentary and volcanic rocks worldwide. An accurate and precise chronology of these geomagnetic field instabilities is fundamental to understanding several aspects of Quaternary climate, dynamo processes, and surface processes. For example, stratigraphic correlation between marine sediment and polar ice records of climate change across the cryospheres benefits from a highly resolved record of reversals and excursions. The temporal patterns of dynamo behavior may reflect physical interactions between the molten outer core and the solid inner core or lowermost mantle. These interactions may control reversal frequency and shape the weak magnetic fields that arise during successive dynamo instabilities. Moreover, weakening of the axial dipole during reversals and excursions enhances the production of cosmogenic isotopes that are used in sediment and ice core stratigraphy and surface exposure dating. The Geomagnetic Instability Time Scale (GITS) is based on the direct dating of transitional polarity states recorded by lava flows using the 40Ar/39Ar method, in parallel with astrochronologic age models of marine sediments in which O isotope and magnetic records have been obtained. A review of data from Quaternary lava flows and sediments yields a GITS comprising 10 polarity reversals and 27 excursions during the past 2.6 million years. Nine of the ten reversals bounding chrons and subchrons are associated with 40Ar/39Ar ages of transitionally-magnetized lava flows. The tenth, the Guass-Matuyama chron boundary, is tightly bracketed by 40Ar/39Ar dated ash deposits. Of the 27 well-documented excursions, 14 occurred during the Matuyama chron and 13 during the Brunhes chron; 19 have been dated directly using the 40Ar/39Ar method on transitionally-magnetized volcanic rocks and form the backbone of the GITS. Excursions are clearly not the rare phenomena once thought. Rather, during the Quaternary period, they occur nearly three times as often as full polarity reversals. I will address analytical issues, including the size and consistency of system blanks, that have led to the recognition of minor (1%) discrepencies between the 40Ar/39Ar age for a particular reversal or excursion and the best astrochronologic estimates from ODP sediment cores. For example, re-analysis of lava flows from Haleakala volcano, Maui that record in detail the Matuyama-Brunhes polarity reversal have been undertaken with blanks an order of magntitude smaller and more stable than was common a decade ago. Using the modern astrochronologic calibration of 28.201 Ma for the age of the Fish Canyon sanidine standard, results thus far yield an 40Ar/39Ar age of 772 × 11 ka for the reversal that is identical to the most precise and accurate astrochronologic age of 773 × 2 ka for this reversal from ODP cores. Similarly, new dating of sanidine in the Cerro Santa Rosa I rhyolite dome, New Mexico reveals an age of 932 × 5 ka for the excursion it records, in perfect agreement with astrochronologically dated ODP core records. Work underway aims at refining the 40Ar/39Ar ages that underpin the entire GITS by further eliminating the bias between the radioisotopic and astrochronologically determined ages for several reversals and excursions.

40Ar/39Ar Dating of Volcanic Glass

NASA Astrophysics Data System (ADS)

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

2007-12-01

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

Extreme-ultraviolet-initiated high-order harmonic generation in Ar+

NASA Astrophysics Data System (ADS)

Clarke, D. D. A.; van der Hart, H. W.; Brown, A. C.

2018-02-01

We employ the R matrix with time dependence method to investigate extreme-ultraviolet-initiated high-order harmonic generation (XIHHG) in Ar+. Using a combination of extreme-ultraviolet (XUV, 92 nm, 3 ×1012W cm-2 ) and time-delayed, infrared (IR, 800 nm, 3 ×1014W cm-2 ) laser pulses, we demonstrate that control over both the mechanism and timing of ionization can afford significant enhancements in the yield of plateau and subthreshold harmonics alike. The presence of the XUV pulse is also shown to alter the relative contribution of different electron emission pathways. Manifestation of the Ar+ electronic structure is found in the appearance of a pronounced Cooper minimum. Interferences among the outer-valence 3 p and inner-valence 3 s electrons are found to incur only a minor suppression of the harmonic intensities, at least for the present combination of XUV and IR laser light. Additionally, the dependence of the XIHHG efficiency on time delay is discussed and rationalized with the aid of classical trajectory simulations.

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.

Three-Dimensional Modeling of Aircraft High-Lift Components with Vehicle Sketch Pad

NASA Technical Reports Server (NTRS)

Olson, Erik D.

2016-01-01

Vehicle Sketch Pad (OpenVSP) is a parametric geometry modeler that has been used extensively for conceptual design studies of aircraft, including studies using higher-order analysis. OpenVSP can model flap and slat surfaces using simple shearing of the airfoil coordinates, which is an appropriate level of complexity for lower-order aerodynamic analysis methods. For three-dimensional analysis, however, there is not a built-in method for defining the high-lift components in OpenVSP in a realistic manner, or for controlling their complex motions in a parametric manner that is intuitive to the designer. This paper seeks instead to utilize OpenVSP's existing capabilities, and establish a set of best practices for modeling high-lift components at a level of complexity suitable for higher-order analysis methods. Techniques are described for modeling the flap and slat components as separate three-dimensional surfaces, and for controlling their motion using simple parameters defined in the local hinge-axis frame of reference. To demonstrate the methodology, an OpenVSP model for the Energy-Efficient Transport (EET) AR12 wind-tunnel model has been created, taking advantage of OpenVSP's Advanced Parameter Linking capability to translate the motions of the high-lift components from the hinge-axis coordinate system to a set of transformations in OpenVSP's frame of reference.

Fluid simulation of species concentrations in capacitively coupled N2/Ar plasmas: Effect of gas proportion

NASA Astrophysics Data System (ADS)

Liang, Ying-Shuang; Liu, Gang-Hu; Xue, Chan; Liu, Yong-Xin; Wang, You-Nian

2017-05-01

A two-dimensional self-consistent fluid model and the experimental diagnostic are employed to investigate the dependencies of species concentrations on the gas proportion in the capacitive N2/Ar discharges operated at 60 MHz, 50 Pa, and 140 W. The results indicate that the N2/Ar proportion has a considerable impact on the species densities. As the N2 fraction increases, the electron density, as well as the Ar+ and Arm densities, decreases remarkably. On the contrary, the N2 + density is demonstrated to increase monotonically with the N2 fraction. Moreover, the N density is observed to increase significantly with the N2 fraction at the N2 fractions below 40%, beyond which it decreases slightly. The electrons are primarily generated via the electron impact ionization of the feed gases. The electron impact ionization of Ar essentially determines the Ar+ density. For the N2 + production, the charge transition process between the Ar+ ions and the feed gas N2 dominates at low N2 fraction, while the electron impact ionization of N2 plays the more important role at high N2 fraction. At any gas mixtures, more than 60% Arm atoms are generated through the radiative decay process from Ar(4p). The dissociation of the feed gas N2 by the excited Ar atoms and by the electrons is responsible for the N formation at low N2 fraction and high N2 fraction, respectively. To validate the simulation results, the floating double probe and the optical emission spectroscopy are employed to measure the total positive ion density and the emission intensity originating from Ar(4p) transitions, respectively. The results from the simulation show a qualitative agreement with that from the experiment, which indicates the reliable model.

Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer

PubMed Central

Siddiqui, Imtiaz A.; Asim, Mohammad; Hafeez, Bilal B.; Adhami, Vaqar M.; Tarapore, Rohinton S.; Mukhtar, Hasan

2011-01-01

Androgen deprivation therapy is the major treatment for advanced prostate cancer (PCa). However, it is a temporary remission, and the patients almost inevitably develop hormone refractory prostate cancer (HRPC). HRPC is almost incurable, although most HRPC cells still express androgen receptor (AR) and depend on the AR for growth, making AR a prime drug target. Here, we provide evidence that epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is a direct antagonist of androgen action. In silico modeling and FRET-based competition assay showed that EGCG physically interacts with the ligand-binding domain of AR by replacing a high-affinity labeled ligand (IC50 0.4 μM). The functional consequence of this interaction was a decrease in AR-mediated transcriptional activation, which was due to EGCG mediated inhibition of interdomain N-C termini interaction of AR. Treatment with EGCG also repressed the transcriptional activation by a hotspot mutant AR (T877A) expressed ectopically as well as the endogenous AR mutant. As the physiological consequence of AR antagonism, EGCG repressed R1881-induced PCa cell growth. In a xenograft model, EGCG was found to inhibit AR nuclear translocation and protein expression. We also observed a significant down-regulation of androgen-regulated miRNA-21 and up-regulation of a tumor suppressor, miRNA-330, in tumors of mice treated with EGCG. Taken together, we provide evidence that EGCG functionally antagonizes androgen action at multiple levels, resulting in inhibition of PCa growth.—Siddiqui, I. A., Asim, M., Hafeez, B. B., Adhami, V. M., Tarapore, R. S., Mukhtar, H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. PMID:21177307

The complement factor 5a receptor 1 has a pathogenic role in chronic inflammation and renal fibrosis in a murine model of chronic pyelonephritis.

PubMed

Choudhry, Naheed; Li, Ke; Zhang, Ting; Wu, Kun-Yi; Song, Yun; Farrar, Conrad A; Wang, Na; Liu, Cheng-Fei; Peng, Qi; Wu, Weiju; Sacks, Steven H; Zhou, Wuding

2016-09-01

Complement factor 5a (C5a) interaction with its receptor (C5aR1) contributes to the pathogenesis of inflammatory diseases, including acute kidney injury. However, its role in chronic inflammation, particularly in pathogen-associated disorders, is largely unknown. Here we tested whether the development of chronic inflammation and renal fibrosis is dependent on C5aR1 in a murine model of chronic pyelonephritis. C5aR1-deficient (C5aR1-/-) mice showed a significant reduction in bacterial load, tubule injury and tubulointerstitial fibrosis in the kidneys following infection, compared with C5aR1-sufficient mice. This was associated with reduced renal leukocyte infiltration specifically for the population of Ly6Chi proinflammatory monocytes/macrophages and reduced intrarenal gene expression of key proinflammatory and profibrogenic factors in C5aR1-/- mice following infection. Antagonizing C5aR1 decreased renal bacterial load, tissue inflammation and tubulointerstitial fibrosis. Ex vivo and in vitro studies showed that under infection conditions, C5a/C5aR1 interaction upregulated the production of proinflammatory and profibrogenic factors by renal tubular epithelial cells and monocytes/macrophages, whereas the phagocytic function of monocytes/macrophages was down-regulated. Thus, C5aR1-dependent bacterial colonization of the tubular epithelium, C5a/C5aR1-mediated upregulation of local inflammatory responses to uropathogenic E. coli and impairment of phagocytic function of phagocytes contribute to persistent bacterial colonization of the kidney, chronic renal inflammation and subsequent tubulointerstitial fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice

PubMed Central

Yang, Jun; Xie, Sheng-Xue; Huang, Yiling; Ling, Min; Liu, Jihong; Ran, Yali; Wang, Yanlin; Thrasher, J Brantley; Berkland, Cory; Li, Benyi

2012-01-01

Background Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft tumor eradication. In this study, we utilized a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct specifically to prostate cancer cells. Materials & methods The biodegradable nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer and the AR shRNA constructs were loaded inside the particles. The surface of the nanoparticles were then conjugated with prostate-specific membrane antigen aptamer A10 for prostate cancer cell-specific targeting. Results A10-conjugation largely enhanced cellular uptake of nanoparticles in both cell culture- and xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was evaluated in xenograft models with different prostate cancer cell lines: 22RV1, LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid tumor regression was observed over 2 weeks. Consistent with previous reports, A10 aptamer conjugation significantly enhanced xenograft tumor regression compared with nonconjugated nanoparticles. Discussion These data demonstrated that tissue-specific delivery of AR shRNA using a biodegradable nanoparticle approach represents a novel therapy for life-threatening prostate cancers. PMID:22583574

Polarization sensitivity of ordered and random antireflective surface structures in silica and spinel

NASA Astrophysics Data System (ADS)

Frantz, J. A.; Selby, J.; Busse, L. E.; Shaw, L. B.; Aggarwal, I. D.; Sanghera, J. S.

2018-02-01

Both ordered and random anti-reflective surface structures (ARSS) have been shown to increase the transmission of an optical surface to >99.9%. These structures are of great interest as an alternative to traditional thin film anti-reflection (AR) coatings for a variety of reasons. Unlike traditional AR coatings, they are patterned directly into the surface of an optic rather than deposited on its surface and are thus not prone to the delamination under thermal cycling that can occur with thin film coatings. Their laser-induced damage thresholds can also be considerably higher. In addition, they provide AR performance over a larger spectral and angular range. It has been previously demonstrated that random ARSSs in silica are remarkably insensitive to incident polarization, with nearly zero variation in transmittance with respect to polarization of the incident beam at fixed wavelength for angles of incidence up to at least 30°. In this work, we evaluate polarization sensitivity of ARSS as a function of wavelength for both random and ordered ARSS. We demonstrate that ordered ARSS is significantly more sensitive to polarization than random ARSS and explain the reason for this difference. In the case of ordered ARSS, we observe significant differences as a function of wavelength, with the transmittance of s- and p-polarized light diverging near the diffraction edge. We present results for both silica and spinel samples and discuss differences observed for these two sets of samples.

Non-expanded dispersion energies and damping functions for Ar 2 and Li 2

NASA Astrophysics Data System (ADS)

Knowles, Peter J.; Meath, William J.

1986-02-01

The non-expanded second-order dispersion energies and damping functions associated with the long-range dispersion energies varying as R-6, R-8and R-10 have been calculated for Ar 2 and Li 2 with the time-dependent Hartree-Fock method, using extended Gaussian basis sets. These results are used to discuss the difficulties associated with ab initio computations of these quantities.

75 FR 49005 - In the Matter of Geotec, Inc., InnoPet Brands Corp., Marbledge Group, Inc. (n/k/a AR Growth...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] In the Matter of Geotec, Inc., InnoPet Brands Corp., Marbledge Group, Inc. (n/k/a AR Growth Finance Corp.), Phlo Corp., Pliant Systems, Inc., Southeast Banking Corp., TNX Television Holdings, Inc., and WestPoint Stevens, Inc.; Order of Suspension of Trading August 10, 2010. It appears to the...

The Space Station air revitalization subsystem design concept

NASA Technical Reports Server (NTRS)

Ray, C. D.; Ogle, K. Y.; Tipps, R. W.; Carrasquillo, R. L.; Wieland, P.

1987-01-01

The current status of the Space Station (SS) Environmental Control and Life Support System (ECLSS) Air Revitalization Subsystem (ARS) design is outlined. ARS performance requirements are provided, along with subsystem options for each ARS function and selected evaluations of the relative merits of each subsystem. Detailed computer models that have been developed to analyze individual subsystem performance capabilities are also discussed. A summary of ARS subsystem level testing planned and completed by NASA Marshall Space Flight Center (MSFC) is given.

Binding of [3H]MSX-2 (3-(3-hydroxypropyl)-7-methyl-8-(m-methoxystyryl)-1-propargylxanthine) to rat striatal membranes--a new, selective antagonist radioligand for A(2A) adenosine receptors.

PubMed

Müller, C E; Maurinsh, J; Sauer, R

2000-01-01

The present study describes the preparation and binding properties of a new, potent, and selective A(2A) adenosine receptor (AR) antagonist radioligand, [3H]3-(3-hydroxypropyl)-7-methyl-8-(m-methoxystyryl)-1-propargy lxanth ine ([3H]MSX-2). [3H]MSX-2 binding to rat striatal membranes was saturable and reversible. Saturation experiments showed that [3H]MSX-2 labeled a single class of binding sites with high affinity (K(d)=8.0 nM) and limited capacity (B(max)=1.16 fmol.mg(-1) of protein). The presence of 100 microM GTP, or 10 mM magnesium chloride, respectively, had no effect on [3H]MSX-2 binding. AR agonists competed with the binding of 1 nM [3H]MSX-2 with the following order of potency: 5'-N-ethylcarboxamidoadenosine (NECA)>2-[4-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxami doaden osine (CGS-21680)>2-chloroadenosine (2-CADO)>N(6)-cyclopentyladenosine (CPA). AR antagonists showed the following order of potency: 8-(m-bromostyryl)-3, 7-dimethyl-1-propargylxanthine (BS-DMPX)>1, 3-dipropyl-8-cyclopentylxanthine (DPCPX)>(R)-5, 6-dimethyl-7-(1-phenylethyl)-2-(4-pyridyl)-7H-pyrrolo[2, 3-d]pyrimidine-4-amine (SH-128)>3,7-dimethyl-1-propargylxanthine (DMPX)>caffeine. The K(i) values for antagonists were in accordance with data from binding studies with the agonist radioligand [3H]CGS21680, while agonist affinities were 3-7-fold lower. [3H]MSX-2 is a highly selective A(2A) AR antagonist radioligand exhibiting a selectivity of at least two orders of magnitude versus all other AR subtypes. The new radioligand shows high specific radioactivity (85 Ci/mmol, 3150 GBq/mmol) and acceptable nonspecific binding at rat striatal membranes of 20-30%, at 1 nM.

Volatile composition of microinclusions in diamonds from the Panda kimberlite, Canada: Implications for chemical and isotopic heterogeneity in the mantle

NASA Astrophysics Data System (ADS)

Burgess, Ray; Cartigny, Pierre; Harrison, Darrell; Hobson, Emily; Harris, Jeff

2009-03-01

In order to better investigate the compositions and the origins of fluids associated with diamond growth, we have carried-out combined noble gas (He and Ar), C and N isotope, K, Ca and halogen (Cl, Br, I) determinations on fragments of individual microinclusion-bearing diamonds from the Panda kimberlite, North West Territories, Canada. The fluid concentrations of halogens and noble gases in Panda diamonds are enriched by several orders of magnitude over typical upper mantle abundances. However, noble gas, C and N isotopic ratios ( 3He/ 4He = 4-6 Ra, 40Ar/ 36Ar = 20,000-30,000, δ 13C = -4.5‰ to -6.9‰ and δ 15N = -1.2‰ to -8.8‰) are within the worldwide range determined for fibrous diamonds and similar to the mid ocean ridge basalt (MORB) source value. The high 36Ar content of the diamonds (>1 × 10 -9 cm 3/g) is at least an order of magnitude higher than any previously reported mantle sample and enables the 36Ar content of the subcontinental lithospheric mantle to be estimated at ˜0.6 × 10 -12 cm 3/g, again similar to estimates for the MORB source. Three fluid types distinguished on the basis of Ca-K-Cl compositions are consistent with carbonatitic, silicic and saline end-members identified in previous studies of diamonds from worldwide sources. These fluid end-members also have distinct halogen ratios (Br/Cl and I/Cl). The role of subducted seawater-derived halogens, originally invoked to explain some of the halogen ratio variations in diamonds, is not considered an essential component in the formation of the fluids. In contrast, it is considered that large halogen fractionation of a primitive mantle ratio occurs during fluid-melt partitioning in forming silicic fluids, and during separation of an immiscible saline fluid.

The influence of aspect ratio and stroke pattern on force generation of a bat-inspired membrane wing.

PubMed

Schunk, Cosima; Swartz, Sharon M; Breuer, Kenneth S

2017-02-06

Aspect ratio (AR) is one parameter used to predict the flight performance of a bat species based on wing shape. Bats with high AR wings are thought to have superior lift-to-drag ratios and are therefore predicted to be able to fly faster or to sustain longer flights. By contrast, bats with lower AR wings are usually thought to exhibit higher manoeuvrability. However, the half-span ARs of most bat wings fall into a narrow range of about 2.5-4.5. Furthermore, these predictions do not take into account the wide variation in flapping motion observed in bats. To examine the influence of different stroke patterns, we measured lift and drag of highly compliant membrane wings with different bat-relevant ARs. A two degrees of freedom shoulder joint allowed for independent control of flapping amplitude and wing sweep. We tested five models with the same variations of stroke patterns, flapping frequencies and wind speed velocities. Our results suggest that within the relatively small AR range of bat wings, AR has no clear effect on force generation. Instead, the generation of lift by our simple model mostly depends on wingbeat frequency, flapping amplitude and freestream velocity; drag is mostly affected by the flapping amplitude.

The influence of aspect ratio and stroke pattern on force generation of a bat-inspired membrane wing

PubMed Central

Swartz, Sharon M.; Breuer, Kenneth S.

2017-01-01

Aspect ratio (AR) is one parameter used to predict the flight performance of a bat species based on wing shape. Bats with high AR wings are thought to have superior lift-to-drag ratios and are therefore predicted to be able to fly faster or to sustain longer flights. By contrast, bats with lower AR wings are usually thought to exhibit higher manoeuvrability. However, the half-span ARs of most bat wings fall into a narrow range of about 2.5–4.5. Furthermore, these predictions do not take into account the wide variation in flapping motion observed in bats. To examine the influence of different stroke patterns, we measured lift and drag of highly compliant membrane wings with different bat-relevant ARs. A two degrees of freedom shoulder joint allowed for independent control of flapping amplitude and wing sweep. We tested five models with the same variations of stroke patterns, flapping frequencies and wind speed velocities. Our results suggest that within the relatively small AR range of bat wings, AR has no clear effect on force generation. Instead, the generation of lift by our simple model mostly depends on wingbeat frequency, flapping amplitude and freestream velocity; drag is mostly affected by the flapping amplitude. PMID:28163875

Genetic and ecological outcomes of Inga vera subsp. affinis (Leguminosae) tree plantations in a fragmented tropical landscape.

PubMed

Cruz Neto, Oswaldo; Aguiar, Antonio V; Twyford, Alex D; Neaves, Linda E; Pennington, R Toby; Lopes, Ariadna V

2014-01-01

Planting of native trees for habitat restoration is a widespread practice, but the consequences for the retention and transmission of genetic diversity in planted and natural populations are unclear. Using Inga vera subsp. affinis as a model species, we genotyped five natural and five planted populations in the Atlantic forest of northeastern Brazil at polymorphic microsatellite loci. We studied the breeding system and population structure to test how much genetic diversity is retained in planted relative to natural populations. We then genotyped seedlings from these populations to test whether genetic diversity in planted populations is restored by outcrossing to natural populations of I. vera. The breeding system of natural I. vera populations was confirmed to be highly outcrossing (t = 0.92; FIS = -0.061, P = 0.04), with populations showing weak population substructure (FST = 0.028). Genetic diversity in planted populations was 50% less than that of natural populations (planted: AR = 14.9, HO = 0.865 and natural: AR = 30.8, HO = 0.655). However, seedlings from planted populations showed a 30% higher allelic richness relative to their parents (seedlings AR = 10.5, parents AR = 7.6). Understanding the processes and interactions that shape this system are necessary to provide ecologically sensible goals and successfully restore hyper-fragmented habitats. Future restoration plans for I. vera must consider the genetic diversity of planted populations and the potential for gene flow between natural populations in the landscape, in order to preserve ecological interactions (i.e. pollination), and promote opportunities for outcrossing.

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.

(234)U/(238)U signatures associated with uranium ore bodies: part 3 Koongarra.

PubMed

Lowson, Richard T

2013-04-01

The Koongarra ore body is an early Proterozoic U ore body in the Alligator Rivers U province, Northern Territory, Australia. It has surface expression with a redox front located ∼30 m below the surface. The (234)U/(238)U activity ratios (AR) for the ground water and the amorphous phase of the solid have been analysed for the ore zone and dispersion halo as a function of depth. The results display a (234)U/(238)U AR signature with depth which may be common to all U ore bodies. The (234)U/(238)U AR is depressed below secular equilibrium in the weathered material above the redox front; rises significantly above secular equilibrium in the vicinity of the redox front; and is followed by a gradual decrease with depth below the redox front. The amplitude of the profile is a function of local conditions. A model is proposed for the signature in which oxidising waters preferentially leach the (234)U sites at the redox front due to preconditioning of the (234)U sites by α recoil during the decay of (23)(8)U to (23)(4)U. Mass balance requires the solid material left behind the redox front to have a (234)U/(238)U AR reduced below 1. Local second order effects may be superimposed on the signature. The signature may have application to calibrating scenarios for nuclear waste repositories, assisting in understanding historical climates, economic evaluation of U ore bodies and U exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Use of circulation types classifications to evaluate AR4 climate models over the Euro-Atlantic region

NASA Astrophysics Data System (ADS)

Pastor, M. A.; Casado, M. J.

2012-10-01

This paper presents an evaluation of the multi-model simulations for the 4th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) in terms of their ability to simulate the ERA40 circulation types over the Euro-Atlantic region in winter season. Two classification schemes, k-means and SANDRA, have been considered to test the sensitivity of the evaluation results to the classification procedure. The assessment allows establishing different rankings attending spatial and temporal features of the circulation types. Regarding temporal characteristics, in general, all AR4 models tend to underestimate the frequency of occurrence. The best model simulating spatial characteristics is the UKMO-HadGEM1 whereas CCSM3, UKMO-HadGEM1 and CGCM3.1(T63) are the best simulating the temporal features, for both classification schemes. This result agrees with the AR4 models ranking obtained when having analysed the ability of the same AR4 models to simulate Euro-Atlantic variability modes. This study has proved the utility of applying such a synoptic climatology approach as a diagnostic tool for models' assessment. The ability of the models to properly reproduce the position of ridges and troughs and the frequency of synoptic patterns, will therefore improve our confidence in the response of models to future climate changes.

Möglichkeiten und Grenzen der Validierung flächenhaft modellierter Nitrateinträge ins Grundwasser mit der N2/Ar-Methode

NASA Astrophysics Data System (ADS)

Eschenbach, Wolfram; Budziak, Dörte; Elbracht, Jörg; Höper, Heinrich; Krienen, Lisa; Kunkel, Ralf; Meyer, Knut; Well, Reinhard; Wendland, Frank

2018-06-01

Valid models for estimating nitrate emissions from agriculture to groundwater are an indispensable forecasting tool. A major challenge for model validation is the spatial and temporal inconsistency between data from groundwater monitoring points and modelled nitrate inputs into groundwater, and the fact that many existing groundwater monitoring wells cannot be used for validation. With the help of the N2/Ar-method, groundwater monitoring wells in areas with reduced groundwater can now be used for model validation. For this purpose, 484 groundwater monitoring wells were sampled in Lower Saxony. For the first time, modelled potential nitrate concentrations in groundwater recharge (from the DENUZ model) were compared with nitrate input concentrations, which were calculated using the N2/Ar method. The results show a good agreement between both methods for glacial outwash plains and moraine deposits. Although the nitrate degradation processes in groundwater and soil merge seamlessly in areas with a shallow groundwater table, the DENUZ model only calculates denitrification in the soil zone. The DENUZ model thus predicts 27% higher nitrate emissions into the groundwater than the N2/Ar method in such areas. To account for high temporal and spatial variability of nitrate emissions into groundwater, a large number of groundwater monitoring points must be investigated for model validation.

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.

2014-12-01

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 thermodynamic and dynamic changes in the atmosphere, such as increases in water vapor content and, thus, precipitation, and shifts in the climatological jet stream. Since AR events are associated with extreme values of integrated water vapor (IWV) near the West Coast, increases in IWV could impact the intensity of AR events intersecting the coast. Additionally, ARs 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. 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. Global climate models have sufficient resolution to simulate synoptic features associated with AR events, such as high values of vertically integrated vapor transport (IVT) approaching the coast. Ten Coupled Model Intercomparison Project (CMIP5) simulations are used to identify changes in ARs impacting the west coast of North America between historical (1970-1999) and end-of-century (2070-2099) runs, using representative concentration pathway (RCP) 8.5. The most extreme ARs are identified in both time periods by the 99th percentile of IVT days along a north-south transect offshore of the coast. Integrated water vapor (IWV) and IVT are predicted to increase, while lower-tropospheric winds change little. Winter-mean precipitation along the West Coast increases by 11-18% (4-6% C-1) while precipitation on extreme IVT days increases by 15-39% (5-19% C-1). The frequency of IVT days above the historical 99th percentile threshold increases as much as 290% by the end of this century.

Mouse models for the study of postnatal cardiac hypertrophy.

PubMed

Del Olmo-Turrubiarte, A; Calzada-Torres, A; Díaz-Rosas, G; Palma-Lara, I; Sánchez-Urbina, R; Balderrábano-Saucedo, N A; González-Márquez, H; Garcia-Alonso, P; Contreras-Ramos, A

2015-06-01

The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH), in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP) isoproterenol (ISO) was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB), neonates (7-15 days) and young adults (6 weeks of age). Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR), alpha and beta myosins (α-MHC, β-MHC) and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS). Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

Exploding Pusher Targets for Electron-Ion Coupling Measurements

NASA Astrophysics Data System (ADS)

Whitley, Heather D.; Pino, Jesse; Schneider, Marilyn; Shepherd, Ronnie; Benedict, Lorin; Bauer, Joseph; Graziani, Frank; Garbett, Warren

2015-11-01

Over the past several years, we have conducted theoretical investigations of electron-ion coupling and electronic transport in plasmas. In the regime of weakly coupled plasmas, we have identified models that we believe describe the physics well, but experimental data is still needed to validate the models. We are currently designing spectroscopic experiments to study electron-ion equilibration and/or electron heat transport using exploding pusher (XP) targets for experiments at the National Ignition Facility. Two platforms are being investigated: an indirect drive XP (IDXP) with a plastic ablator and a polar-direct drive XP (PDXP) with a glass ablator. The fill gas for both designs is D2. We propose to use a higher-Z dopant, such as Ar, as a spectroscopic tracer for time-resolved electron and ion temperature measurements. We perform 1D simulations using the ARES hydrodynamic code, in order to produce the time-resolved plasma conditions, which are then post-processed with CRETIN to assess the feasibility of a spectroscopic measurement. We examine target performance with respect to variations in gas fill pressure, ablator thickness, atom fraction of the Ar dopant, and drive energy, and assess the sensitivity of the predicted spectra to variations in the models for electron-ion equilibration and thermal conductivity. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-675219.

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

Measurements and kinetic modeling of atomic species in fuel-oxidizer mixtures excited by a repetitive nanosecond pulse discharge

NASA Astrophysics Data System (ADS)

Winters, C.; Eckert, Z.; Yin, Z.; Frederickson, K.; Adamovich, I. V.

2018-01-01

This work presents the results of number density measurements of metastable Ar atoms and ground state H atoms in diluted mixtures of H2 and O2 with Ar, as well as ground state O atoms in diluted H2-O2-Ar, CH4-O2-Ar, C3H8-O2-Ar, and C2H4-O2-Ar mixtures excited by a repetitive nanosecond pulse discharge. The measurements have been made in a nanosecond pulse, double dielectric barrier discharge plasma sustained in a flow reactor between two plane electrodes encapsulated within dielectric material, at an initial temperature of 500 K and pressures ranging from 300 Torr to 700 Torr. Metastable Ar atom number density distribution in the afterglow is measured by tunable diode laser absorption spectroscopy, and used to characterize plasma uniformity. Temperature rise in the reacting flow is measured by Rayleigh scattering. H atom and O atom number densities are measured by two-photon absorption laser induced fluorescence. The results are compared with kinetic model predictions, showing good agreement, with the exception of extremely lean mixtures. O atoms and H atoms in the plasma are produced mainly during quenching of electronically excited Ar atoms generated by electron impact. In H2-Ar and O2-Ar mixtures, the atoms decay by three-body recombination. In H2-O2-Ar, CH4-O2-Ar, and C3H8-O2-Ar mixtures, O atoms decay in a reaction with OH, generated during H atom reaction with HO2, with the latter produced by three-body H atom recombination with O2. The net process of O atom decay is O  +  H  →  OH, such that the decay rate is controlled by the amount of H atoms produced in the discharge. In extra lean mixtures of propane and ethylene with O2-Ar the model underpredicts the O atom decay rate. At these conditions, when fuel is completely oxidized by the end of the discharge burst, the net process of O atom decay, O  +  O  →  O2, becomes nearly independent of H atom number density. Lack of agreement with the data at these conditions is likely due to diffusion of H atoms from the partially oxidized regions near the side walls of the reactor into the plasma. Although significant fractions of hydrogen and hydrocarbon fuels are oxidized by O atoms produced in the plasma, chain branching remains a minor effect at these relatively low temperature conditions.

Properties of some statistics for AR-ARCH model with application to technical analysis

NASA Astrophysics Data System (ADS)

Huang, Xudong; Liu, Wei

2009-03-01

In this paper, we investigate some popular technical analysis indexes for AR-ARCH model as real stock market. Under the given conditions, we show that the corresponding statistics are asymptotically stationary and the law of large numbers hold for frequencies of the stock prices falling out normal scope of these technical analysis indexes under AR-ARCH, and give the rate of convergence in the case of nonstationary initial values, which give a mathematical rationale for these methods of technical analysis in supervising the security trends.

Medium- and Long-term Prediction of LOD Change with the Leap-step Autoregressive Model

NASA Astrophysics Data System (ADS)

Liu, Q. B.; Wang, Q. J.; Lei, M. F.

2015-09-01

It is known that the accuracies of medium- and long-term prediction of changes of length of day (LOD) based on the combined least-square and autoregressive (LS+AR) decrease gradually. The leap-step autoregressive (LSAR) model is more accurate and stable in medium- and long-term prediction, therefore it is used to forecast the LOD changes in this work. Then the LOD series from EOP 08 C04 provided by IERS (International Earth Rotation and Reference Systems Service) is used to compare the effectiveness of the LSAR and traditional AR methods. The predicted series resulted from the two models show that the prediction accuracy with the LSAR model is better than that from AR model in medium- and long-term prediction.

32 CFR Appendix C to Subpart M of... - Authorized Activities for Maneuver Training Area Access

Code of Federal Regulations, 2010 CFR

2010-07-01

... commercial use (AR 405-80) Installation service and maintenance (AR 420-74, FL Reg 350-30) Non-DoD personnel...-1) Horseback riding on roads and vehicle tracks Walking, distance running Model airplane and rocket...) Installation service and maintenance (AR 420-74) Non-Commercial recreational use: Hunting, fishing and trapping...

New Approach To Hour-By-Hour Weather Forecast

NASA Astrophysics Data System (ADS)

Liao, Q. Q.; Wang, B.

2017-12-01

Fine hourly forecast in single station weather forecast is required in many human production and life application situations. Most previous MOS (Model Output Statistics) which used a linear regression model are hard to solve nonlinear natures of the weather prediction and forecast accuracy has not been sufficient at high temporal resolution. This study is to predict the future meteorological elements including temperature, precipitation, relative humidity and wind speed in a local region over a relatively short period of time at hourly level. By means of hour-to-hour NWP (Numeral Weather Prediction)meteorological field from Forcastio (https://darksky.net/dev/docs/forecast) and real-time instrumental observation including 29 stations in Yunnan and 3 stations in Tianjin of China from June to October 2016, predictions are made of the 24-hour hour-by-hour ahead. This study presents an ensemble approach to combine the information of instrumental observation itself and NWP. Use autoregressive-moving-average (ARMA) model to predict future values of the observation time series. Put newest NWP products into the equations derived from the multiple linear regression MOS technique. Handle residual series of MOS outputs with autoregressive (AR) model for the linear property presented in time series. Due to the complexity of non-linear property of atmospheric flow, support vector machine (SVM) is also introduced . Therefore basic data quality control and cross validation makes it able to optimize the model function parameters , and do 24 hours ahead residual reduction with AR/SVM model. Results show that AR model technique is better than corresponding multi-variant MOS regression method especially at the early 4 hours when the predictor is temperature. MOS-AR combined model which is comparable to MOS-SVM model outperform than MOS. Both of their root mean square error and correlation coefficients for 2 m temperature are reduced to 1.6 degree Celsius and 0.91 respectively. The forecast accuracy of 24- hour forecast deviation no more than 2 degree Celsius is 78.75 % for MOS-AR model and 81.23 % for AR model.

Liquid crystal true 3D displays for augmented reality applications

NASA Astrophysics Data System (ADS)

Li, Yan; Liu, Shuxin; Zhou, Pengcheng; Chen, Quanming; Su, Yikai

2018-02-01

Augmented reality (AR) technology, which integrates virtual computer-generated information into the real world scene, is believed to be the next-generation human-machine interface. However, most AR products adopt stereoscopic 3D display technique, which causes the accommodation-vergence conflict. To solve this problem, we have proposed two approaches. The first is a multi-planar volumetric display using fast switching polymer-stabilized liquid crystal (PSLC) films. By rapidly switching the films between scattering and transparent states while synchronizing with a high-speed projector, the 2D slices of a 3D volume could be displayed in time sequence. We delved into the research on developing high-performance PSLC films in both normal mode and reverse mode; moreover, we also realized the demonstration of four-depth AR images with correct accommodation cues. For the second approach, we realized a holographic AR display using digital blazed gratings and a 4f system to eliminate zero-order and higher-order noise. With a 4k liquid crystal on silicon device, we achieved a field of view (FOV) of 32 deg. Moreover, we designed a compact waveguidebased holographic 3D display. In the design, there are two holographic optical elements (HOEs), each of which functions as a diffractive grating and a Fresnel lens. Because of the grating effect, holographic 3D image light is coupled into and decoupled out of the waveguide by modifying incident angles. Because of the lens effect, the collimated zero order light is focused at a point, and got filtered out. The optical power of the second HOE also helps enlarge FOV.

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.

The androgen receptor malignancy shift in prostate cancer.

PubMed

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

2018-05-01

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

Contractile dysfunction in muscle may underlie androgen-dependent motor dysfunction in spinal bulbar muscular atrophy

PubMed Central

Oki, Kentaro; Halievski, Katherine; Vicente, Laura; Xu, Youfen; Zeolla, Donald; Poort, Jessica; Katsuno, Masahisa; Adachi, Hiroaki; Sobue, Gen; Wiseman, Robert W.; Breedlove, S. Marc

2015-01-01

Spinal and bulbar muscular atrophy (SBMA) is characterized by progressive muscle weakness linked to a polyglutamine expansion in the androgen receptor (AR). Current evidence indicates that mutant AR causes SBMA by acting in muscle to perturb its function. However, information about how muscle function is impaired is scant. One fundamental question is whether the intrinsic strength of muscles, an attribute of muscle independent of its mass, is affected. In the current study, we assess the contractile properties of hindlimb muscles in vitro from chronically diseased males of three different SBMA mouse models: a transgenic (Tg) model that broadly expresses a full-length human AR with 97 CAGs (97Q), a knock-in (KI) model that expresses a humanized AR containing a CAG expansion in the first exon, and a Tg myogenic model that overexpresses wild-type AR only in skeletal muscle fibers. We found that hindlimb muscles in the two Tg models (97Q and myogenic) showed marked losses in their intrinsic strength and resistance to fatigue, but were minimally affected in KI males. However, diseased muscles of all three models showed symptoms consistent with myotonic dystrophy type 1, namely, reduced resting membrane potential and deficits in chloride channel mRNA. These data indicate that muscle dysfunction is a core feature of SBMA caused by at least some of the same pathogenic mechanisms as myotonic dystrophy. Thus mechanisms controlling muscle function per se independent of mass are prime targets for SBMA therapeutics. PMID:25663674

Vibration based condition monitoring of a multistage epicyclic gearbox in lifting cranes

NASA Astrophysics Data System (ADS)

Assaad, Bassel; Eltabach, Mario; Antoni, Jérôme

2014-01-01

This paper proposes a model-based technique for detecting wear in a multistage planetary gearbox used by lifting cranes. The proposed method establishes a vibration signal model which deals with cyclostationary and autoregressive models. First-order cyclostationarity is addressed by the analysis of the time synchronous average (TSA) of the angular resampled vibration signal. Then an autoregressive model (AR) is applied to the TSA part in order to extract a residual signal containing pertinent fault signatures. The paper also explores a number of methods commonly used in vibration monitoring of planetary gearboxes, in order to make comparisons. In the experimental part of this study, these techniques are applied to accelerated lifetime test bench data for the lifting winch. After processing raw signals recorded with an accelerometer mounted on the outside of the gearbox, a number of condition indicators (CIs) are derived from the TSA signal, the residual autoregressive signal and other signals derived using standard signal processing methods. The goal is to check the evolution of the CIs during the accelerated lifetime test (ALT). Clarity and fluctuation level of the historical trends are finally considered as a criteria for comparing between the extracted CIs.

An Approximately 4.35 Ga Ar-Ar Age for GRA 8 and the Complex Chronology of its Parent Body

NASA Technical Reports Server (NTRS)

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

2010-01-01

GRA06128 and GRA06129 (hereafter GRA 8 and GRA 9) are partial melts of a parent body of approximately chondritic composition. We reported a conventional Sm-147-Nd-143 isochron age of 4.559+/-0.096 Ga and a 146 Sm-142Nd model age of 4.549+/-0.036 for combined data for the two rocks. Plagioclase plus whole rock and leachate (approx.phosphate) samples gave a secondary Sm-147-Nd-143 age of 3.4+/-0.4 Ga. An Ar-39-Ar-40 age of 4.460+/-0.028 Ga was interpreted as dating metamorphism in GRA 9. We report Ar-39-Ar-40 ages in the range approx.4344-4366 Ma for GRA 8, establishing similar but different Ar-39-Ar-40 ages for the two rocks, consistent with their different Sr-isotopic systematics, and discuss these ages in the context of the complex sequence of events that affected these samples.

An Approximately 4.35 Ga Ar-Ar Age for GRA 8 and the Complex Chronology of its Parent Body

NASA Technical Reports Server (NTRS)

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

2010-01-01

GRA06128 and GRA06129 (hereafter GRA 8 and GRA 9) are partial melts of a parent body of approximately chondritic composition. We reported a conventional SM-147Sm-ND_143 isochron age of 4.559 +/-.096 Ga and a SM-146-142Nd model age of 4.549 +/- 0.036 for combined data for the two rocks. Plagioclase plus whole rock and leachate (approximately phosphate) samples gave a secondary SM-147-ND-143 age of 3.4 +/-0.4 Ga. An Ar-39-Ar-40 age of 4.460+/-0.028 Ga was interpreted by as dating metamorphism in GRA 9. We report Ar-39-Ar-40 ages in the range approximately 4344-4366 Ma for GRA 8, establishing similar but different Ar-39-Ar-40 ages for the two rocks, consistent with their different Sr-istopic systematics, and discuss these ages in the context of the complex sequence of events that affected these samples

Experimental study of 38Ar+α reaction cross sections relevant to the 41Ca abundance in the solar system

NASA Astrophysics Data System (ADS)

Talwar, R.; Bojazi, M. J.; Mohr, P.; Auranen, K.; Avila, M. L.; Ayangeakaa, A. D.; Harker, J.; Hoffman, C. R.; Jiang, C. L.; Kuvin, S. A.; Meyer, B. S.; Rehm, K. E.; Santiago-Gonzalez, D.; Sethi, J.; Ugalde, C.; Winkelbauer, J. R.

2018-05-01

In massive stars, the 41Ca(n ,α )38Ar and 41K(p ,α )38Ar reactions have been identified as the key reactions governing the abundance of 41Ca, which is considered as a potential chronometer for solar system formation. So far, due to experimental limitations, the 41Ca(n ,α )38Ar reaction rate is solely based on statistical model calculations. In the present study, we have measured the time-inverse 38Ar(α ,n )41Ca and 38Ar(α ,p )41K reactions using an active target detector. The reactions were studied in inverse kinematics using a 133-MeV 38Ar beam and 4He as the active-gas target. Both excitation functions were measured simultaneously in the energy range of 6.8 ≤Ec .m .≤9.3 MeV. Using detailed balance the 41Ca(n ,α )38Ar and 41K(p ,α )38Ar reaction rates were determined, which suggested a 20% increase in the 41Ca yield from massive stars.

Comprehensive data resources and analytical tools for pathological association of aminoacyl tRNA synthetases with cancer

PubMed Central

Lee, Ji-Hyun; You, Sungyong; Hyeon, Do Young; Kang, Byeongsoo; Kim, Hyerim; Park, Kyoung Mii; Han, Byungwoo; Hwang, Daehee; Kim, Sunghoon

2015-01-01

Mammalian cells have cytoplasmic and mitochondrial aminoacyl-tRNA synthetases (ARSs) that catalyze aminoacylation of tRNAs during protein synthesis. Despite their housekeeping functions in protein synthesis, recently, ARSs and ARS-interacting multifunctional proteins (AIMPs) have been shown to play important roles in disease pathogenesis through their interactions with disease-related molecules. However, there are lacks of data resources and analytical tools that can be used to examine disease associations of ARS/AIMPs. Here, we developed an Integrated Database for ARSs (IDA), a resource database including cancer genomic/proteomic and interaction data of ARS/AIMPs. IDA includes mRNA expression, somatic mutation, copy number variation and phosphorylation data of ARS/AIMPs and their interacting proteins in various cancers. IDA further includes an array of analytical tools for exploration of disease association of ARS/AIMPs, identification of disease-associated ARS/AIMP interactors and reconstruction of ARS-dependent disease-perturbed network models. Therefore, IDA provides both comprehensive data resources and analytical tools for understanding potential roles of ARS/AIMPs in cancers. Database URL: http://ida.biocon.re.kr/, http://ars.biocon.re.kr/ PMID:25824651

Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms.

PubMed

Feng, J; Li, L; Zhang, N; Liu, J; Zhang, L; Gao, H; Wang, G; Li, Y; Zhang, Y; Li, X; Liu, D; Lu, J; Huang, B

2017-05-18

The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin. In vivo, DHT promotes metastasis in a nude mouse model, and AR and LSD1 are indispensable in this process. We establish that higher expression of nucleus AR to cytoplasm AR associated with worse prognostic outcomes in breast cancer patient samples. This study maps an 'androgen-AR/LSD1-target genes' pathway in breast carcinogenesis, implicating the importance of hormonal balance in women, and the potential clinical significance of serum androgen and AR in prediction of breast cancer and selection of breast cancer therapy.

β2‑adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

PubMed

Roca, Reyes; Esteban, Pablo; Zapater, Pedro; Inda, María-Del-Mar; Conte, Anna Lucia; Gómez-Escolar, Laura; Martínez, Helena; Horga, José F; Palazon, José M; Peiró, Ana M

2018-06-01

The present study was designed to investigate the functional status of β2 adrenoceptors (β2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The β2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte β2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren‑Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10‑9 to 10‑4 mM), and β2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. β2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the β2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the β2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.

Effect of oral tolerance in a mouse model of allergic rhinitis.

PubMed

Shin, Ji-Hyeon; Kang, Jun Myung; Kim, Sung Won; Cho, Jin-Hee; Park, Yong Jin; Kim, Soo Whan

2010-03-01

Induction of oral tolerance (OT) is known to prevent allergic inflammation in models of asthma. This study investigated the preventive effect of OT and airway remodeling in a mouse model of allergic rhinitis (AR). An in vivo study using an animal model. Catholic Research Institutes of Medical Science. Forty six-week-old, female BALB/c mice were divided into four groups: control, AR, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/aluminum hydroxide, 1 mg for six days in the low-dose OT group and a 25 mg single dose in the high-dose OT group. Mice in the AR group were fed phosphate-buffered saline. After sensitization followed by challenges with OVA during six weeks, nasal behaviors, interleukin (IL)-13 and interferon gamma (IFN-gamma) levels in nasal lavage (NAL) fluids, as well as OVA-specific IgE levels in serum, were measured. The degree of goblet cell hyperplasia and thickness of lamina propria were observed in nasal tissues by periodic acid-Schiff and Masson's trichrome stain. A P value < 0.05 was accepted as statistically significant. Both OT groups showed a significant decrease in inflammatory cells, IL-13 and IFN-gamma in NAL fluids, as well as OVA-specific IgE levels in serum compared with the AR group. In addition, the degree of goblet cell hyperplasia and thickness of lamina propria were attenuated in both OT groups compared with the AR group. Further, these alterations did not differ significantly between the two OT groups. These results suggest that OT may effectively reduce allergic inflammation as well as airway remodeling in a mouse model of AR. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

ACTH Action on StAR Biology

PubMed Central

Clark, Barbara J.

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

ACTH Action on StAR Biology.

PubMed

Clark, Barbara J

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

PubMed

Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

2015-02-01

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Development of a multi-variate calibration approach for quantitative analysis of oxidation resistant Mo-Si-B coatings using laser ablation inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Cakara, Anja; Bonta, Maximilian; Riedl, Helmut; Mayrhofer, Paul H.; Limbeck, Andreas

2016-06-01

Nowadays, for the production of oxidation protection coatings in ultrahigh temperature environments, alloys of Mo-Si-B are employed. The properties of the material, mainly the oxidation resistance, are strongly influenced by the Si to B ratio; thus reliable analytical methods are needed to assure exact determination of the material composition for the respective applications. For analysis of such coatings, laser ablation inductively coupled mass spectrometry (LA-ICP-MS) has been reported as a versatile method with no specific requirements on the nature of the sample. However, matrix effects represent the main limitation of laser-based solid sampling techniques and usually the use of matrix-matched standards for quantitative analysis is required. In this work, LA-ICP-MS analysis of samples with known composition and varying Mo, Si and B content was carried out. Between known analyte concentrations and derived LA-ICP-MS signal intensities no linear correlation could be found. In order to allow quantitative analysis independent of matrix effects, a multiple linear regression model was developed. Besides the three target analytes also the signals of possible argides (40Ar36Ar and 98Mo40Ar) as well as detected impurities of the Mo-Si-B coatings (108Pd) were considered. Applicability of the model to unknown samples was confirmed using external validation. Relative deviations from the values determined using conventional liquid analysis after sample digestion between 5 and 10% for the main components Mo and Si were observed.

Point-contact Andreev reflection spectroscopy on Bi 2 Se 3 single crystals

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

Granstrom, C. R.; Fridman, I.; Lei, H. -C.

In order to study how Andreev reflection (AR) occurs between a superconductor and a three-dimensional topological insulator (TI), we use superconducting Nb tips to perform point-contact AR spectroscopy at 4.2 K on as-grown single crystals of Bi 2Se 3. Scanning tunneling spectroscopy and scanning tunneling microscopy are also used to characterize the superconducting tip and both the doping level and surface condition of the TI sample. Furthermore, the point-contact measurements show clear spectral signatures of AR, as well as a depression of zero-bias conductance with decreasing junction impedance. The latter observation can be attributed to interfacial Rashba spin-orbit coupling, andmore » the presence of bulk bands at the Fermi level in our samples suggests that bulk states of Bi2Se3 are involved in the observed AR.« less

Point-contact Andreev reflection spectroscopy on Bi 2 Se 3 single crystals

DOE PAGES

Granstrom, C. R.; Fridman, I.; Lei, H. -C.; ...

2016-04-27

In order to study how Andreev reflection (AR) occurs between a superconductor and a three-dimensional topological insulator (TI), we use superconducting Nb tips to perform point-contact AR spectroscopy at 4.2 K on as-grown single crystals of Bi 2Se 3. Scanning tunneling spectroscopy and scanning tunneling microscopy are also used to characterize the superconducting tip and both the doping level and surface condition of the TI sample. Furthermore, the point-contact measurements show clear spectral signatures of AR, as well as a depression of zero-bias conductance with decreasing junction impedance. The latter observation can be attributed to interfacial Rashba spin-orbit coupling, andmore » the presence of bulk bands at the Fermi level in our samples suggests that bulk states of Bi2Se3 are involved in the observed AR.« less

A Solution Space for a System of Null-State Partial Differential Equations: Part 3

NASA Astrophysics Data System (ADS)

Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the third of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations (PDEs) in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE κ ). The system comprises 2 N null-state equations and three conformal Ward identities that govern CFT correlation functions of 2 N one-leg boundary operators. In the first two articles (Flores and Kleban, in Commun Math Phys, arXiv:1212.2301, 2012; Commun Math Phys, arXiv:1404.0035, 2014), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. Extending these results, we prove in this article that dim and entirely consists of (real-valued) solutions constructed with the CFT Coulomb gas (contour integral) formalism. In order to prove this claim, we show that a certain set of C N such solutions is linearly independent. Because the formulas for these solutions are complicated, we prove linear independence indirectly. We use the linear injective map of Lemma 15 in Flores and Kleban (Commun Math Phys, arXiv:1212.2301, 2012) to send each solution of the mentioned set to a vector in , whose components we find as inner products of elements in a Temperley-Lieb algebra. We gather these vectors together as columns of a symmetric matrix, with the form of a meander matrix. If the determinant of this matrix does not vanish, then the set of C N Coulomb gas solutions is linearly independent. And if this determinant does vanish, then we construct an alternative set of C N Coulomb gas solutions and follow a similar procedure to show that this set is linearly independent. The latter situation is closely related to CFT minimal models. We emphasize that, although the system of PDEs arises in CFT in away that is typically non-rigorous, our treatment of this system here and in Flores and Kleban (Commun Math Phys, arXiv:1212.2301, 2012; Commun Math Phys, arXiv:1404.0035, 2014; Commun Math Phys, arXiv:1405.2747, 2014) is completely rigorous.

Diffusive loss of argon in response to melt vein formation in polygenetic impact melt breccias

NASA Astrophysics Data System (ADS)

Mercer, Cameron M.; Hodges, Kip V.

2017-08-01

Many planetary surfaces in the solar system have experienced prolonged bombardment. With each impact, new rocks can be assembled that incorporate freshly generated impact melts with fragments of older rocks. Some breccias can become polygenetic, containing multiple generations of impact melt products, and can potentially provide important insights into the extensive bombardment history of a region. However, the amount of chronological information that can be extracted from such samples depends on how well the mineral isotopic systems of geochronometers can preserve the ages of individual melt generations without being disturbed by younger events. We model the thermal evolution of impact melt veins and the resulting loss of Ar from K-bearing phases common in impact melt breccias to assess the potential for preserving the 40Ar/39Ar ages of individual melt generations. Our model results demonstrate that millimeter-scale, clast-free melt veins cause significant heating of adjacent host rock minerals and can cause detectable Ar loss in contact zones that are generally thinner than, and at most about the same thickness as, the vein width. The incorporation of cold clasts in melt veins reduces the magnitudes of heating and Ar loss in the host rocks, and Ar loss can be virtually undetectable for sufficiently clast-rich veins. Quantitative evidence of the timing of impacts, as measured with the 40Ar/39Ar method, can be preserved in polygenetic impact melt breccias, particularly for those containing millimeter-scale bodies of clast-bearing melt products.

Spectral shapes of rovibrational lines of CO broadened by He, Ar, Kr and SF6: A test case of the Hartmann-Tran profile

NASA Astrophysics Data System (ADS)

Ngo, N. H.; Lin, H.; Hodges, J. T.; Tran, H.

2017-12-01

High signal-to-noise ratio spectra of the (3-0) band P(1) and P(17) lines of CO broadened by He, Ar, Kr and SF6 were measured with a frequency-stabilized cavity ring-down spectroscopy system. For each collision-partner and both lines, multiple spectra were measured over pressures spanning nearly three decades up to 130 kPa. These data were analyzed with a multispectrum fitting procedure. Line shapes were modeled using the Hartmann-Tran (HT) profile with first-order line mixing as well as several other simplified profiles. The results show that for all considered collision partners (with the exception of SF6), the HT profile captures the measured line shapes with maximum absolute residuals that are within 0.1% of the peak absorption. In the case of SF6, which is the heaviest perturber investigated here, the maximum residuals for the HT profile are twice as large as for the other collision partners.

Influence of platelet aspect ratio on the mechanical behaviour of bio-inspired nanocomposites using molecular dynamics.

PubMed

Mathiazhagan, S; Anup, S

2016-06-01

Superior mechanical properties of biocomposites such as nacre and bone are attributed to their basic building blocks. These basic building blocks have nanoscale features and play a major role in achieving combined stiffening, strengthening and toughening mechanisms. Bioinspired nanocomposites based on these basic building blocks, regularly and stairwise staggered arrangements of hard platelets in soft matrix, have huge potential for developing advanced materials. The study of applicability of mechanical principles of biological materials to engineered materials will guide designing advanced materials. To probe the generic mechanical characteristics of these bioinspired nanocomposites, the model material concept in molecular dynamics (MD) is used. In this paper, the effect of platelets aspect ratio (AR) on the mechanical behaviour of bioinspired nanocomposites is investigated. The obtained Young׳s moduli of both the models and the strengths of the regularly staggered models agree with the available theories. However, the strengths of the stairwise staggered models show significant difference. For the stairwise staggered model, we demonstrate the existence of two critical ARs, a smaller critical AR above which platelet fracture occurs and a higher critical AR above which composite strength remains constant. Our MD study also shows the existence of mechanisms of platelet pull-out and breakage for lower and higher ARs. Pullout mechanism acts as a major source of plasticity. Further, we find that the regularly staggered model can achieve an optimal combination of high Young׳s modulus, flow strength and toughness, and the stairwise staggered model is efficient in obtaining high Young׳s modulus and tensile strength. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Situ Observations of Agglomeration of Non-metallic Inclusions at Steel/Ar and Steel/Slag Interfaces by High-Temperature Confocal Laser Scanning Microscope: A Review

NASA Astrophysics Data System (ADS)

Mu, Wangzhong; Dogan, Neslihan; Coley, Kenneth S.

2018-05-01

The agglomeration behavior of non-metallic inclusions in the steelmaking process is important for controlling the cleanliness of the steel. In this work, the observation of agglomeration behaviors of inclusions at steel/Ar and steel/slag interfaces using a high-temperature confocal laser scanning microscope (HT-CLSM) is summarized. This HT-CLSM technique has been applied to observe phase transformation during solidification and heat treatment and the engulfment and pushing behavior of inclusions in front of the solidified interface. In the current work, the inclusion agglomeration behavior at steel/Ar and steel/slag interfaces is summarized and discussed. Subsequently, the development of the theoretical work investigating inclusion agglomeration at steel/Ar and steel/slag interfaces including the initial capillary force model and Kralchevsky-Paunov model is described. Finally, the Kralchevsky-Paunov model is applied to investigating nitride inclusion agglomeration at high-manganese steel/Ar interfaces. This work aims to give a critical review of the application of HT-CLSM in secondary refining as well as a better control of inclusion elimination for clean steel production.

VUV Emission of Microwave Driven Argon Plasma Source

NASA Astrophysics Data System (ADS)

Henriques, Julio; Espinho, Susana; Felizardo, Edgar; Tatarova, Elena; Dias, Francisco; Ferreira, Carlos

2013-09-01

An experimental and kinetic modeling investigation of a low-pressure (0.1-1.2 mbar), surface wave (2.45 GHz) induced Ar plasma as a source vacuum ultraviolet (VUV) light is presented, using visible and VUV optical spectroscopy. The electron density and the relative VUV emission intensities of excited Ar atoms (at 104.8 nm and 106.6 nm) and ions (at 92.0 nm and 93.2 nm) were determined as a function of the microwave power and pressure. The experimental results were analyzed using a 2D self-consistent theoretical model based on a set of coupled equations including the electron Boltzmann equation, the rate balance equations for the most important electronic excited species and for charged particles, the gas thermal balance equation, and the wave electrodynamics. The principal collisional and radiative processes for neutral Ar(3p54s) and Ar(3p54p) and ionized Ar(3s3p6 2S1/2) levels are accounted for. Model predictions are in good agreement with the experimental measurements. This study was funded by the Foundation for Science and Technology, Portuguese Ministry of Education and Science, under the research contract PTDC/FIS/108411/2008.

Potassium Isotopic Compositions of NIST Potassium Standards and 40Ar/39Ar Mineral Standards

NASA Technical Reports Server (NTRS)

Morgan, Leah; Tappa, Mike; Ellam, Rob; Mark, Darren; Higgins, John; Simon, Justin I.

2013-01-01

Knowledge of the isotopic ratios of standards, spikes, and reference materials is fundamental to the accuracy of many geochronological methods. For example, the 238U/235U ratio relevant to U-Pb geochronology was recently re-determined [1] and shown to differ significantly from the previously accepted value employed during age determinations. These underlying values are fundamental to accurate age calculations in many isotopic systems, and uncertainty in these values can represent a significant (and often unrecognized) portion of the uncertainty budget for determined ages. The potassium isotopic composition of mineral standards, or neutron flux monitors, is a critical, but often overlooked component in the calculation of K-Ar and 40Ar/39Ar ages. It is currently assumed that all terrestrial materials have abundances indistinguishable from that of NIST SRM 985 [2]; this is apparently a reasonable assumption at the 0.25per mille level (1s) [3]. The 40Ar/39Ar method further relies on the assumption that standards and samples (including primary and secondary standards) have indistinguishable 40K/39K values. We will present data establishing the potassium isotopic compositions of NIST isotopic K SRM 985, elemental K SRM 999b, and 40Ar/39Ar biotite mineral standard GA1550 (sample MD-2). Stable isotopic compositions (41K/39K) were measured by the peak shoulder method with high resolution MC-ICP-MS (Thermo Scientific NEPTUNE Plus), using the accepted value of NIST isotopic SRM 985 [2] for fractionation [4] corrections [5]. 40K abundances were measured by TIMS (Thermo Scientific TRITON), using 41K/39K values from ICP-MS measurements (or, for SRM 985, values from [2]) for internal fractionation corrections. Collectively these data represent an important step towards a metrologically traceable calibration of 40K concentrations in primary 40Ar/39Ar mineral standards and improve uncertainties by ca. an order of magnitude in the potassium isotopic compositions of standards.

Investigation of galvanic corrosion in laser-welded stainless steel sheets

NASA Astrophysics Data System (ADS)

Kwok, Chi-Tat; Fong, Siu Lung; Cheng, Fai Tsun; Man, Hau-Chung

2004-10-01

In the present study, bead-on-plate specimens of 1-mm sheets of austenitic and duplex stainless steels were fabricated by laser penetration welding with a 2.5-kW CW Nd:YAG laser. The galvanic corrosion behavior of laser-weldment (LW) against as-received (AR) specimens with an area rato of 1:1 in 3.5% NaCL solution was studied by means of a zero-resistance ammeter. The free corrosion potentials of as-received specimens were found to be considerably higher than those of laser weldments, indicating that the weldments are more active and always act as anodes. The ranking of galvanic current densities (IG) of the couples in ascending order is: AR S31603-LW S31603 < AR S31803-LW S31803 < AR S32760-LW S32760 < AR S30400-LW S30400. For the galvanic couple between AR S30400 and LW S30400, the IG is the highest (78.6 nA/cm2) because large amount of δ-ferrite in the weld zone acts as active sites. On the other hand, the IG of the galvanic couple between AR S31603 and LW S31603 is the lowest (-26 nA/cm2) because no δ-ferrite is present after laser welding. The recorded IG of all couples revealed constantly low values (in the rnage of nA/cm2) and sometimes stayed negative, which indicated polarity reversal.

[Fundamental aspects for accrediting medical equipment calibration laboratories in Colombia].

PubMed

Llamosa-Rincón, Luis E; López-Isaza, Giovanni A; Villarreal-Castro, Milton F

2010-02-01

Analysing the fundamental methodological aspects which should be considered when drawing up calibration procedure for electro-medical equipment, thereby permitting international standard-based accreditation of electro-medical metrology laboratories in Colombia. NTC-ISO-IEC 17025:2005 and GTC-51-based procedures for calibrating electro-medical equipment were implemented and then used as patterns. The mathematical model for determining the estimated uncertainty value when calibrating electro-medical equipment for accreditation by the Electrical Variable Metrology Laboratory's Electro-medical Equipment Calibration Area accredited in compliance with Superintendence of Industry and Commerce Resolution 25771 May 26th 2009 consists of two equations depending on the case; they are: E = (Ai + sigmaAi) - (Ar + sigmaAr + deltaAr1) and E = (Ai + sigmaAi) - (Ar + sigmaA + deltaAr1). The mathematical modelling implemented for measuring uncertainty in the Universidad Tecnológica de Pereira's Electrical Variable Metrology Laboratory (Electro-medical Equipment Calibration Area) will become a good guide for calibration initiated in other laboratories in Colombia and Latin-America.

Dynamical and thermodynamical modulations of future changes in landfalling atmospheric rivers over North America

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

Gao, Yang; Lu, Jian; Leung, Lai-Yung R.

This study examines the changes of landfalling atmospheric rivers (ARs) over the west coast of North America in response to future warming using model outputs from the Coupled Model Intercomparison Project phase 5 (CMIP5). The result reveals a strikingly large magnitude of increase of AR days by the end of the 21st century in the RCP8.5 climate change scenario, with fractional increases ranging between ~50% and 600%, depending on the seasons and the landfall locations. These increases are predominantly controlled by the super-Clausius-Clapeyron rate of increase of atmospheric water vapor with warming, while changes of winds that transport moisture inmore » the ARs, or dynamical effect, mostly counter the thermodynamical effect of increasing water vapor, limiting the increase of AR events in the future. The consistent negative effect of wind changes on AR days during spring and fall can be further linked to the robust poleward shift of the subtropical jet in the North Pacific basin.« less

High Precision 40Ar/39Ar Geochronology of Servilleta Basalts of the Rio Grande Gorge, New Mexico

NASA Astrophysics Data System (ADS)

Cosca, M. A.; Thompson, R. A.; Turner, K. J.

2014-12-01

New geologic mapping and high-precision 40Ar/39Ar geochronology within the Taos Plateau in northern New Mexico indicate a period of vigorous volcanic activity between ~5.5 and ~1 Ma. Over 50 visible volcanic centers formed during this time together with an unresolved number of vents, fissures, and volcanic centers buried by intercalated volcanic rock and sedimentary basin fill. Defining the volcanic stratigraphy is essential for models of regional groundwater flow and for understanding the geologic evolution of the Pliocene to Recent Rio Grande rift. A spectacular stratigraphic section of volcanic rock related to Rio Grande rifting is visible from the High Bridge, just a few miles outside of Taos, NM, where a 240 m canyon is incised through the basal, middle, and upper Servilleta basalt flow packages (Dungan et al., 1984). Fresh basalt from a vertical transect of the canyon near the High Bridge were analyzed by 40Ar/39Ar methods on ~3 mm3 rock fragments using an ARGUS VI mass spectrometer and the resulting 40Ar/39Ar ages define a precise emplacement chronology of the entire stratigraphic section. The basal flow package records ages of 4.78 ± 0.03 Ma (relative to FCT sanidine = 28.204 Ma; all errors 2 sigma) at river level, 4.77 ± 0.03 Ma at mid flow, and 4.50 ± 0.04 Ma at the top of the flow. The middle flow package records ages of 4.11 ± 0.03 Ma at the base of the flow, 4.08 ± 0.04 Ma mid flow, and 4.02 ± 0.06 Ma at the top of the flow. The upper basalt package records ages of 3.69 ± 0.06 Ma at the base of the flow and 3.59 ± 0.08 Ma at the top of the flow. These data support rapid effusion of voluminous lava flows on time scales of 100-200 ka. Two reddish paleosols separating the Servilleta packages each developed during a 400 ka period of volcanic quiescence. First order calculations using exposed lava thicknesses in the gorge and areal exposures suggest each flow package represents emplacement of ~200 km3 of basalt. Because no exposed vent of appropriate age has been identified that could produce such basalt volumes, the Servilleta basalts probably erputed from buried vents and/or fissures, possibly oriented along the northwest trending fault systems defining the Rio Grande rift graben.

Affordances of Augmented Reality in Science Learning: Suggestions for Future Research

NASA Astrophysics Data System (ADS)

Cheng, Kun-Hung; Tsai, Chin-Chung

2013-08-01

Augmented reality (AR) is currently considered as having potential for pedagogical applications. However, in science education, research regarding AR-aided learning is in its infancy. To understand how AR could help science learning, this review paper firstly has identified two major approaches of utilizing AR technology in science education, which are named as image- based AR and location- based AR. These approaches may result in different affordances for science learning. It is then found that students' spatial ability, practical skills, and conceptual understanding are often afforded by image-based AR and location-based AR usually supports inquiry-based scientific activities. After examining what has been done in science learning with AR supports, several suggestions for future research are proposed. For example, more research is required to explore learning experience (e.g., motivation or cognitive load) and learner characteristics (e.g., spatial ability or perceived presence) involved in AR. Mixed methods of investigating learning process (e.g., a content analysis and a sequential analysis) and in-depth examination of user experience beyond usability (e.g., affective variables of esthetic pleasure or emotional fulfillment) should be considered. Combining image-based and location-based AR technology may bring new possibility for supporting science learning. Theories including mental models, spatial cognition, situated cognition, and social constructivist learning are suggested for the profitable uses of future AR research in science education.

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.

Argon-40 as a Constraint on the Volcanic Degassing History and Thermal Evolution of Mars

NASA Astrophysics Data System (ADS)

Kiefer, W. S.

2017-12-01

Models for the thermal and magmatic evolution of Mars are strongly controlled by the volcanic degassing of water from the interior. Water affects the mantle's viscosity and hence the vigor of convective flow. It also affects the mantle's solidus temperature and hence the rate of magma generation. This set of coupled feedback loops affects both the volume of crustal production and the possible production of a magnetic field via a core dynamo (e.g., Sandu and Kiefer, GRL 2012, 2011GL050225). Volcanic degassing also affects other atmospheric components. Argon-40, which is a radioactive decay product of potassium-40, can potentially serve as an additional test of thermal evolution models. As a noble gas, 40Ar is highly incompatible in mantle and crustal rocks and thus tends to degas to the atmosphere during magmatic events. 40K has a half-life of 1.25 billion years and thus 40Ar measures volcanic degassing throughout martian history. It is relatively insensitive to atmospheric loss processes during the earliest part of solar system history, and long-term loss of 40Ar from the atmosphere can be estimated from fractionation of the 38Ar/36Ar ratio relative to solar (MAVEN results indicate that 66% of 36Ar has been lost from the martian atmosphere, Jakosky et al., Science 2017). The noble gas composition of the martian atmosphere has been measured both in situ using the SAM mass spectrometer on NASA's Curiosity rover and via measurements of trapped atmospheric gases in martian meteorites. One important application of 40Ar degassing models is as a constraint on the bulk silicate composition of Mars. The most widely accepted composition model for Mars has a potassium abundance of 305-310 ppm, slightly higher than the bulk silicate Earth. However, several other models assume a bulk silicate Mars K of up to 1040 ppm. Preliminary Ar degassing modeling favors K in the lower half of this range, consistent with results from long-term and present-day magma production models. Constraints on the bulk silicate K abundance are important to understanding the thermal and magmatic history of Mars because 40K is a radioactive heat source. In addition, the expected abundances of K and Na are correlated and elevated values of Na act to lower the peridotite solidus and thus to enhance the magma production rate (Kiefer et al., Geochimica, 2015).

Spectrum of Th-Ar Hollow Cathode Lamps

National Institute of Standards and Technology Data Gateway

SRD 161 NIST Spectrum of Th-Ar Hollow Cathode Lamps (Web, free access)   This atlas presents observations of the infra-red (IR) spectrum of a low current Th-Ar hollow cathode lamp with the 2-m Fourier transform spectrometer (FTS) at NIST. These observations establish more than 2400 lines that are suitable for use as wavelength standards in the range 691 nm to 5804 nm. The observations were made in collaboration with the European Southern Observatory (ESO), in order to provide calibration reference data for new high-resolution Echelle spectrographs, such as the Cryogenic High-Resolution IR Echelle Spectrograph ([CRIRES]), ESO's new IR spectrograph at the Very Large Telescope in Chile.

A time series model: First-order integer-valued autoregressive (INAR(1))

NASA Astrophysics Data System (ADS)

Simarmata, D. M.; Novkaniza, F.; Widyaningsih, Y.

2017-07-01

Nonnegative integer-valued time series arises in many applications. A time series model: first-order Integer-valued AutoRegressive (INAR(1)) is constructed by binomial thinning operator to model nonnegative integer-valued time series. INAR (1) depends on one period from the process before. The parameter of the model can be estimated by Conditional Least Squares (CLS). Specification of INAR(1) is following the specification of (AR(1)). Forecasting in INAR(1) uses median or Bayesian forecasting methodology. Median forecasting methodology obtains integer s, which is cumulative density function (CDF) until s, is more than or equal to 0.5. Bayesian forecasting methodology forecasts h-step-ahead of generating the parameter of the model and parameter of innovation term using Adaptive Rejection Metropolis Sampling within Gibbs sampling (ARMS), then finding the least integer s, where CDF until s is more than or equal to u . u is a value taken from the Uniform(0,1) distribution. INAR(1) is applied on pneumonia case in Penjaringan, Jakarta Utara, January 2008 until April 2016 monthly.

Metabolic analysis of the increased adventitious rooting mutant of Artemisia annua reveals a role for the plant monoterpene borneol in adventitious root formation.

PubMed

Tian, Na; Liu, Shuoqian; Li, Juan; Xu, Wenwen; Yuan, Lin; Huang, Jianan; Liu, Zhonghua

2014-08-01

Adventitious root (AR) formation is a critical process for plant clonal propagation. The role of plant secondary metabolites in AR formation is still poorly understood. Chemical and physical mutagenesis in combination with somatic variation were performed on Artemisia annua in order to obtain a mutant with changes in adventitious rooting and composition of plant secondary metabolites. Metabolic and morphological analyses of the iar (increased adventitious rooting) mutant coupled with in vitro assays were used to elucidate the relationship between plant secondary metabolites and AR formation. The only detected differences between the iar mutant and wild-type were rooting capacity and borneol/camphor content. Consistent with this, treatment with borneol in vitro promoted adventitious rooting in wild-type. The enhanced rooting did not continue upon removal of borneol. The iar mutant displayed no significant differences in AR formation upon treatment with camphor. Together, our results suggest that borneol promotes adventitious rooting whereas camphor has no effect on AR formation. © 2013 Scandinavian Plant Physiology Society.

Zebrafish (Danio rerio) androgen receptor: sequence homology and up-regulation by the fungicide vinclozolin.

PubMed

Smolinsky, Amanda N; Doughman, Jennifer M; Kratzke, Liên-Thành C; Lassiter, Christopher S

2010-03-01

Steroid hormones regulate gene expression in organisms by binding to receptor proteins. These hormones include the androgens, which signal through androgen receptors (ARs). Endocrine disrupters (EDCs) are chemicals in the environment that adversely affect organisms by binding to nuclear receptors, including ARs. Vinclozolin, a fungicide used on fruit and vegetable crops, is a known anti-androgen, a type of EDC that blocks signals from testosterone and its derivatives. In order to better understand the effects of EDCs, further research on androgen receptors and other hormone signaling pathways is necessary. In this study, we demonstrate the evolutionary conservation between the genomic structure of the human and zebrafish ar genes and find that ar mRNA expression increases in zebrafish embryos exposed to vinclozolin, which may be evolutionarily conserved as well. At 48 and 72 h post-fertilization, vinclozolin-treated embryos express ar mRNA 8-fold higher than the control level. These findings suggest that zebrafish embryos attempt to compensate for the presence of an anti-androgen by increasing the number of androgen receptors available.

Comparative study of the Ar and He atmospheric pressure plasmas on E-cadherin protein regulation for plasma-mediated transdermal drug delivery

NASA Astrophysics Data System (ADS)

Lee, Hyun Young; Hae Choi, Jeong; Hong, Jin Woo; Kim, Gyoo Cheon; Lee, Hae June

2018-05-01

The effects of argon plasma (ArP) and helium plasma (HeP) jets on E-cadherin protein function have been tested in order to choose the working gas for a better plasma-mediated transdermal drug delivery. The plasma-mediated changes of the E-cadherin function and the skin penetration efficacies of epidermal growth factor (EGF) were monitored in vitro using HaCaT human keratinocytes and in vivo using hairless mice. The ArP showed higher efficacy for E-cadherin regulation and EGF absorption than HeP under the same applied voltage and the same gas flow rate. The ArP generates higher volume power density, higher discharge current peak, and more reactive species than HeP, especially for OH with the same operating parameters. Moreover, the effect of ArP on E-cadherin function was blocked by the use of a grounded metal mesh. Taken together, this study presents the possibility that the synergetic effect of negative charges with radicals plays an important role in plasma-mediated E-cadherin regulation, which leads to enhanced transdermal drug delivery.

Improvement of an automated protein crystal exchange system PAM for high-throughput data collection

PubMed Central

Hiraki, Masahiko; Yamada, Yusuke; Chavas, Leonard M. G.; Wakatsuki, Soichi; Matsugaki, Naohiro

2013-01-01

Photon Factory Automated Mounting system (PAM) protein crystal exchange systems are available at the following Photon Factory macromolecular beamlines: BL-1A, BL-5A, BL-17A, AR-NW12A and AR-NE3A. The beamline AR-NE3A has been constructed for high-throughput macromolecular crystallography and is dedicated to structure-based drug design. The PAM liquid-nitrogen Dewar can store a maximum of three SSRL cassettes. Therefore, users have to interrupt their experiments and replace the cassettes when using four or more of them during their beam time. As a result of investigation, four or more cassettes were used in AR-NE3A alone. For continuous automated data collection, the size of the liquid-nitrogen Dewar for the AR-NE3A PAM was increased, doubling the capacity. In order to check the calibration with the new Dewar and the cassette stand, calibration experiments were repeatedly performed. Compared with the current system, the parameters of the novel system are shown to be stable. PMID:24121334

Utilization of ICU Data to Improve 30 and 60 Day HENRE Mortality Models, Revision 1

DTIC Science & Technology

2017-05-12

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary...a large dose of radiation in a short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an...individual may experience the hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in

A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants

PubMed Central

Sun, Feng; Indran, Inthrani R.; Zhang, Zhi Wei; Tan, M.H.Eileen; Li, Yu; Lim, Z.L.Ryan; Hua, Rui; Yang, Chong; Soon, Fen-Fen; Li, Jun; Xu, H.Eric; Cheung, Edwin; Yong, Eu-Leong

2015-01-01

Persistent androgen receptor (AR) signaling is the key driving force behind progression and development of castration-resistant prostate cancer (CRPC). In many patients, AR COOH-terminal truncated splice variants (ARvs) play a critical role in contributing to the resistance against androgen depletion therapy. Unfortunately, clinically used antiandrogens like bicalutamide (BIC) and enzalutamide (MDV), which target the ligand binding domain, have failed to suppress these AR variants. Here, we report for the first time that a natural prenylflavonoid, icaritin (ICT), can co-target both persistent AR and ARvs. ICT was found to inhibit transcription of key AR-regulated genes, such as KLK3 [prostate-specific antigen (PSA)] and ARvs-regulated genes, such as UBE2C and induce apoptosis in AR-positive prostate cancer (PC) cells. Mechanistically, ICT promoted the degradation of both AR and ARvs by binding to arylhydrocarbon-receptor (AhR) to mediate ubiquitin-proteasomal degradation. Therefore, ICT impaired AR transactivation in PC cells. Knockdown of AhR gene restored AR stability and partially prevented ICT-induced growth suppression. In clinically relevant murine models orthotopically implanted with androgen-sensitive and CRPC cells, ICT was able to target AR and ARvs, to inhibit AR signaling and tumor growth with no apparent toxicity. Our results provide a mechanistic framework for the development of ICT, as a novel lead compound for AR-positive PC therapeutics, especially for those bearing AR splice variants. PMID:25908644

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Atmospheric rivers moisture transport from a Lagrangian perspective

NASA Astrophysics Data System (ADS)

Ramos, A. M.; Nieto, R.; Tomé, R.; Gimeno, L.; Trigo, R. M.; Liberato, M. L. R.; Lavers, D. A.

2015-12-01

An automated atmospheric rivers (ARs) detection algorithm is used for the North Atlantic Ocean Basin allowing the identification of the major ARs that affected western European coasts between 1979 and 2014 over the winter half-year (October to March). The entire west coast of Europe was divided into five domains, namely, the Iberian Peninsula (9.75° W; 36-43.75° N), France (4.5° W; 43.75-50° N), UK (4.5° W; 50-59° N), southern Scandinavia and the Netherlands (5.25° E; 50-59° N), and northern Scandinavia (5.25° E; 59-70° N). Following the identification of the main ARs that made landfall in western Europe, a Lagrangian analysis was then applied in order to identify the main sources of moisture that reach each domain. The Lagrangian dataset used was obtained from the FLEXPART model global simulation from 1979 to 2012, where the atmosphere was divided into approximately 2.0 million parcels, and it was forced by ERA-Interim reanalysis on a 1° latitude-longitude grid. Results show that, in general, for all regions considered, the major climatological source of moisture extends along the subtropical North Atlantic, from the Florida Peninsula (northward of 20° N), to each sink region, with the nearest coast to each sink region always appearing as a local maximum of evaporation. In addition, during the AR events, the Atlantic subtropical source is reinforced and displaced, with a slight northward movement of the moisture sources is found when the sink region is positioned at higher latitudes. In conclusion, the results confirm the advection of moisture linked to ARs from subtropical ocean areas, but also the existence of a tropical one, and the mid-latitude sources further the analysed longitude along the North Atlantic is located eastward.

Combined Effect of an Atmospheric River and a Cut-off Low in Hiroshima Flooding Event on August 19, 2014

NASA Astrophysics Data System (ADS)

Takayabu, Y. N.; Hirota, N.; Kato, M.; Arakane, S.

2015-12-01

An extraordinary precipitation over 100 mmhr-1in Hiroshima on August 19, 2014, caused a flash flood which resulted in 74 fatalities and collapse of 330 houses. In order to examine the meteorological background of this flooding event, we carried out a detailed analysis utilizing rain gauge data, satellite precipitation dataset, and a meso scale and a global scale objective analyses provided from the Japan Meteorological Agency. Then, we performed numerical experiments using a nonhydrostatic compressible equation model called the Cloud-Resolving Storm Simulator (CReSS). As a result, a combined effect of an atmospheric river (AR) and a cut-off low (COL) in this flooding event was elucidated. During the event, a filamentary transport of moisture extending from the Indochina Peninsula to the Japanese Islands was observed along the southern side of the subtropical jet, forming an AR. This AR had a deep structure with an amount of free tropospheric moisture comparable to that of the boundary layer. Concurrently, there was a COL, detached from the Mid-Pacific Trough, moving northwestward toward the Japanese Archipelago. With various sensitivity experiments, we concluded that a mid-tropospheric instability associated with the cold core of the COL and a dynamical ascent induced in its foreside, collaboratively worked with the anomalous moisture in the free troposphere associated with the AR, to extraordinarily enhance the precipitation over Hiroshima region. An orographic effect to concentrate the precipitation in this region was also confirmed. An implication on a difference in effects of AR in this event with a climatologically moist boundary layer, from those in the US west coast with a very dry environment, was also obtained. Acknowledgment: This study is supported by the Environment Research and Technology Development Fund (2-1503) of the Ministry of the Environment, Japan, and by the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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

USGS Publications Warehouse

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

2011-01-01

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

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

The Yeast Anaerobic Response Element AR1b Regulates Aerobic Antifungal Drug-dependent Sterol Gene Expression*

PubMed Central

Gallo-Ebert, Christina; Donigan, Melissa; Liu, Hsing-Yin; Pascual, Florencia; Manners, Melissa; Pandya, Devanshi; Swanson, Robert; Gallagher, Denise; Chen, WeiWei; Carman, George M.; Nickels, Joseph T.

2013-01-01

Saccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis in mammals, is regulated at the transcriptional level by a sterol feedback mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 7-bp consensus SRE is identical to the anaerobic response element, AR1c. Data indicate that Upc2 and Ecm22 function through binding to this SRE site. We now show that it is two novel anaerobic AR1b elements in the UPC2 promoter that direct global ERG gene expression in response to a block in de novo ergosterol biosynthesis, brought about by antifungal drug treatment. The AR1b elements are absolutely required for auto-induction of UPC2 gene expression and protein and require Upc2 and Ecm22 for function. We further demonstrate the direct binding of recombinant expressed S. cerevisiae ScUpc2 and pathogenic Candida albicans CaUpc2 and Candida glabrata CgUpc2 to AR1b and SRE/AR1c elements. Recombinant endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in trans to regulate ergosterol gene expression. Our results indicate that Upc2 must occupy UPC2 AR1b elements in order for ERG gene expression induction to take place. Thus, the two UPC2-AR1b elements drive expression of all ERG genes necessary for maintaining normal antifungal susceptibility, as wild type cells lacking these elements have increased susceptibility to azole antifungal drugs. Therefore, targeting these specific sites for antifungal therapy represents a novel approach to treat systemic fungal infections. PMID:24163365

Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle.

PubMed

Chino, Daisuke; Sone, Tomoyo; Yamazaki, Kumi; Tsuruoka, Yuri; Yamagishi, Risa; Shiina, Shunsuke; Obara, Keisuke; Yamaki, Fumiko; Higai, Koji; Tanaka, Yoshio

2018-01-01

Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10 -7 M). Atenolol (a selective β 1 -AR antagonist; 3 × 10 -7 -10 -6  M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA 2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β 2 -AR antagonist) at 10 -9 -10 -8  M, but was competitively antagonized by 10 -7 -3 × 10 -7  M, with a pA 2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10 -7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA 2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β 1 -AR and β 3 -AR.

Modeling of block copolymer dry etching for directed self-assembly lithography

NASA Astrophysics Data System (ADS)

Belete, Zelalem; Baer, Eberhard; Erdmann, Andreas

2018-03-01

Directed self-assembly (DSA) of block copolymers (BCP) is a promising alternative technology to overcome the limits of patterning for the semiconductor industry. DSA exploits the self-assembling property of BCPs for nano-scale manufacturing and to repair defects in patterns created during photolithography. After self-assembly of BCPs, to transfer the created pattern to the underlying substrate, selective etching of PMMA (poly (methyl methacrylate)) to PS (polystyrene) is required. However, the etch process to transfer the self-assemble "fingerprint" DSA patterns to the underlying layer is still a challenge. Using combined experimental and modelling studies increases understanding of plasma interaction with BCP materials during the etch process and supports the development of selective process that form well-defined patterns. In this paper, a simple model based on a generic surface model has been developed and an investigation to understand the etch behavior of PS-b-PMMA for Ar, and Ar/O2 plasma chemistries has been conducted. The implemented model is calibrated for etch rates and etch profiles with literature data to extract parameters and conduct simulations. In order to understand the effect of the plasma on the block copolymers, first the etch model was calibrated for polystyrene (PS) and poly (methyl methacrylate) (PMMA) homopolymers. After calibration of the model with the homopolymers etch rate, a full Monte-Carlo simulation was conducted and simulation results are compared with the critical-dimension (CD) and selectivity of etch profile measurement. In addition, etch simulations for lamellae pattern have been demonstrated, using the implemented model.

Realization of a collection of reference minerals to develop a technique for in situ dating of the Martian rocks

NASA Astrophysics Data System (ADS)

Cattani, F.; Gillot, P. Y.; Hildenbrand, A.; Quidelleur, X.; Courtade, F.; Boukari, C.; Lefevre, J. C.

2017-12-01

Absolute dating within ± 20% is needed to check and to calibrate the relative Martian chronology presently available. For that purpose, a K-Ar dating system has been developed to experiment the feasibility of such dating in future landing planetary missions. It consists in a laser ablation-based system built to vaporize a reproducible volume of rock. Potassium content is measured by laser-induced breakdown spectroscopy (LIBS) and argon by quadrupole mass spectrometry (QMS). Improvements of LIBS acquisition (optimization of optics part and normalization by total intensity spectrum) and QMS calibration (by reproducible known amount of argon) have been achieved. In addition, we have test the determination of ablated mass from volume measurement performed by profilometry technique. Instrument calibration for Martian analyses requires terrestrial analogues to determine the most suitable analytical conditions. For that purpose, total chemistry, electron microprobe analyses, flame absorption spectrometry and mass spectrometry have been performed in order to qualify stoichiometry, mineralogy, K concentration and Ar content from a collection of old terrestrial rocks. These analyses coupled with those published have helped to select 14 mineral phases (e.g. feldspars) showing a large range of K content (0.15 - 11%). The objective is to calibrate the LIBS on different geological material with Mars-like %K values ( 0.4%), and assess the detection limit of the LIBS with extreme %K values. All these mineral phases display a K-Ar age older than 260 Ma. Hence, the content of radiogenic Ar atoms per gram is within the range of Martian samples (on the order of 1 Ga for 0.4 %K). Furthermore, the ablated mass is estimated by measurement of Ar extracted from an analogue mineral of known amount of radiogenic Ar content per gram. This quantification is then compared with the mass estimated from the volume measured by profilometry technique. Finally, it provides a well-defined relationship between the ablation time and the type of ablated mineral. Experiments have been conducted to test our dating system for rocks with similar features than those from the Martian surface. Our preliminary results show that our QMS and LIBS instruments are suitable for in-situ K-Ar analyses with an uncertainty for K-Ar age much better than 15%.

"Asparagus Racemosus" Enhances Memory and Protects against Amnesia in Rodent Models

ERIC Educational Resources Information Center

Ojha, Rakesh; Sahu, Alakh N.; Muruganandam, A. V.; Singh, Gireesh Kumar; Krishnamurthy, Sairam

2010-01-01

"Asparagus Racemosus" (AR) is an Ayurvedic rasayana possessing multiple neuropharmacological activities. The adpatogenic and antidepressant activity of AR is well documented. The present study was undertaken to assess nootropic and anti-amnesic activities of MAR in rats. The Morris water maze (MWM) and elevated plus maze (EPM) models were employed…

Androgen signaling in myocytes contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue.

PubMed

Ophoff, Jill; Van Proeyen, Karen; Callewaert, Filip; De Gendt, Karel; De Bock, Katrien; Vanden Bosch, An; Verhoeven, Guido; Hespel, Peter; Vanderschueren, Dirk

2009-08-01

Muscle frailty is considered a major cause of disability in the elderly and chronically ill. However, the exact role of androgen receptor (AR) signaling in muscle remains unclear. Therefore, a postmitotic myocyte-specific AR knockout (mARKO) mouse model was created and investigated together with a mouse model with ubiquitous AR deletion. Muscles from mARKO mice displayed a marked reduction in AR protein (60-88%). Interestingly, body weights and lean body mass were lower in mARKO vs. control mice (-8%). The weight of the highly androgen-sensitive musculus levator ani was significantly reduced (-46%), whereas the weights of other peripheral skeletal muscles were not or only slightly reduced. mARKO mice had lower intra-abdominal fat but did not demonstrate a cortical or trabecular bone phenotype, indicating that selective ablation of the AR in myocytes affected male body composition but not skeletal homeostasis. Furthermore, muscle contractile performance in mARKO mice did not differ from their controls. Myocyte-specific AR ablation resulted in a conversion of fast toward slow fibers, without affecting muscle strength or fatigue. Similar results were obtained in ubiquitous AR deletion, showing lower body weight, whereas some but not all muscle weights were reduced. The percent slow fibers was increased, but no changes in muscle strength or fatigue could be detected. Together, our findings show that myocyte AR signaling contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. The levator ani weight remains the most sensitive and specific marker of AR-mediated anabolic action on muscle.

Exclusion of aldose reductase as a mediator of ERG deficits in a mouse model of diabetic eye disease.

PubMed

Samuels, Ivy S; Lee, Chieh-Allen; Petrash, J Mark; Peachey, Neal S; Kern, Timothy S

2012-11-01

Streptozotocin (STZ)-induced diabetes is associated with reductions in the electrical response of the outer retina and retinal pigment epithelium (RPE) to light. Aldose reductase (AR) is the first enzyme required in the polyol-mediated metabolism of glucose, and AR inhibitors have been shown to improve diabetes-induced electroretinogram (ERG) defects. Here, we used control and AR -/- mice to determine if genetic inactivation of this enzyme likewise inhibits retinal electrophysiological defects observed in a mouse model of type 1 diabetes. STZ was used to induce hyperglycemia and type 1 diabetes. Diabetic and age-matched nondiabetic controls of each genotype were maintained for 22 weeks, after which ERGs were used to measure the light-evoked components of the RPE (dc-ERG) and the neural retina (a-wave, b-wave). In comparison to their nondiabetic controls, wildtype (WT) and AR -/- diabetic mice displayed significant decreases in the c-wave, fast oscillation, and off response components of the dc-ERG but not in the light peak response. Nondiabetic AR -/- mice displayed larger ERG component amplitudes than did nondiabetic WT mice; however, the amplitude of dc-ERG components in diabetic AR -/- animals were similar to WT diabetics. ERG a-wave amplitudes were not reduced in either diabetic group, but b-wave amplitudes were lower in WT and AR -/-diabetic mice. These findings demonstrate that the light-induced responses of the RPE and outer retina are disrupted in diabetic mice, but these defects are not due to photoreceptor dysfunction, nor are they ameliorated by deletion of AR. This latter finding suggests that benefits observed in other studies utilizing pharmacological inhibitors of AR might have been secondary to off-target effects of the drugs.

Nanoscale organization of {beta}{sub 2}-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

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

Vobornik, Dusan; Rouleau, Yanouchka; Haley, Jennifer

2009-04-24

Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize {beta}{sub 2}-adrenergic receptors ({beta}{sub 2}AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the {beta}{sub 2}AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline,more » the size of domains containing the {beta}{sub 2}AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of {beta}{sub 2}AR are observed in the membrane of the HEK293 cells that stably overexpress {beta}{sub 2}AR-GFP and {beta}{sub 2}AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use {beta}{sub 2}AR-Venus fusion proteins as models for {beta}{sub 2}AR function. These observations are critical for designing future cell models and assays based on {beta}{sub 2}AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.« less

New Possibilities for the Accurate in Situ Determination of Chalcophile and Siderophile Trace Elements by Laser Ablation Collision and Reaction Cell ICP-MS

NASA Astrophysics Data System (ADS)

Mason, P. R.

2004-05-01

Our knowledge of how chalcophile and siderophile elements partition in minerals is limited, mainly due to the lack of suitable techniques for their accurate in situ determination. Host minerals (e.g. sulphides) are typically of small size (<30 μ m) and highly heterogeneous in composition, requiring analysis of high spatial resolution. Concentrations of chalcophile elements in silicates and oxides are low (sub μ gg-1) and thus challenging to measure. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), offering high sensitivity and good spatial resolution (10-100 μ m) is thus highly suited for this purpose. Unfortunately, the widespread use of this technique has been limited by enhanced problems specific to chalcophile and siderophile elements. These include inaccuracy due to the presence of spectral interferences, elemental fractionation during ablation/ionization and the lack of suitable calibration standards. Polyatomic spectral interferences, present either as a background component (e.g. O2+, ArAr+) or based around the recombination of matrix elements with argon (e.g. ArS+, ArNi+) hinder accurate analysis. These depend upon the relative concentrations of major matrix components and trace elements to be measured and are significant in many relevant minerals (e.g. sulphides). The use of a collision and reaction cells in ICP-MS is a new method for selective interference attenuation, significantly improving detection limits for elements such as Fe, S and Se by between 1 and 4 orders of magnitude. ArNi+ and ArCu+ interferences in sulphides can be attenuated by at least an order of magnitude leading to improved accuracy for the measurement of the Platinum Group elements Rh and Ru. Sulphur isotopes can be measured interference-free at m/z=32 and 34 by eliminating background O2+. These improvements open up new possibilities for the use of LA-ICP-MS in trace element and isotopic studies at the lowest concentration levels or where sample preparation creates additional problems (e.g. NiS fire assay beads). I will give examples of applications for this technique in the study of ore minerals, meteorites and precipitates from hydrothermal vents.

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.

Syringic Acid Extracted from Herba dendrobii Prevents Diabetic Cataract Pathogenesis by Inhibiting Aldose Reductase Activity

PubMed Central

Wei, Xiaoyong; Chen, Dan; Yi, Yanchun; Qi, Hui; Gao, Xinxin; Fang, Hua; Gu, Qiong; Wang, Ling; Gu, Lianquan

2012-01-01

Objective. Effects of Syringic acid (SA) extracted from dendrobii on diabetic cataract (DC) pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17 μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC. PMID:23365598

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

PubMed

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

2010-01-01

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

Advancements in cosmogenic 38Ar exposure dating of terrestrial rocks

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Effects of a Proteasome Inhibitor on Cardiomyocytes in a Pressure-Overload Hypertrophy Rat Model: An Animal Study.

PubMed

Kim, In-Sub; Jo, Won-Min

2017-06-01

The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and NF-κB was measured in the left ventricle. Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not NF-κB, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, NF-κB expression levels were not related to UPS function.

Molecular modeling of the effects of 40Ar recoil in illite particles on their K-Ar isotope dating

NASA Astrophysics Data System (ADS)

Szczerba, Marek; Derkowski, Arkadiusz; Kalinichev, Andrey G.; Środoń, Jan

2015-06-01

The radioactive decay of 40K to 40Ar is the basis of isotope age determination of micaceous clay minerals formed during diagenesis. The difference in K-Ar ages between fine and coarse grained illite particles has been interpreted using detrital-authigenic components system, its crystallization history or post-crystallization diffusion. Yet another mechanism should also be considered: natural 40Ar recoil. Whether this recoil mechanism can result in a significant enough loss of 40Ar to provide observable decrease of K-Ar age of the finest illite crystallites at diagenetic temperatures - is the primary objective of this study which is based on molecular dynamics (MD) computer simulations. All the simulations were performed for the same kinetic energy (initial velocity) of the 40Ar atom, but for varying recoil angles that cover the entire range of their possible values. The results show that 40Ar recoil can lead to various deformations of the illite structure, often accompanied by the displacement of OH groups or breaking of the Si-O bonds. Depending on the recoil angle, there are four possible final positions of the 40Ar atom with respect to the 2:1 layer at the end of the simulation: it can remain in the interlayer space or end up in the closest tetrahedral, octahedral or the opposite tetrahedral sheet. No simulation angles were found for which the 40Ar atom after recoil passes completely through the 2:1 layer. The energy barrier for 40Ar passing through the hexagonal cavity from the tetrahedral sheet into the interlayer was calculated to be 17 kcal/mol. This reaction is strongly exothermic, therefore there is almost no possibility for 40Ar to remain in the tetrahedral sheet of the 2:1 layer over geological time periods. It will either leave the crystal, if close enough to the edge, or return to the interlayer space. On the other hand, if 40Ar ends up in the octahedral sheet after recoil, a substantially higher energy barrier of 55 kcal/mol prevents it from leaving the TOT layer over geological time. Based on the results of MD simulations, the estimates of the potential effect of 40Ar recoil on the K-Ar dating of illite show that some of 40Ar is lost and the loss is substantially dependent on the crystallite dimensions. The 40Ar loss can vary from 10% for the finest crystallites (two 2:1 layers thickness and <0.02 μm in diameter) to close to zero for the thickest and largest (in the ab plane) ones. Because the decrease of the K-Ar estimated age is approximately proportional to the 40Ar loss, the finer crystallites show lower apparent age than the coarser ones, although the age of crystallization is assumed equal for all the crystallites. From the model it is also clear that the lack of K removal from illite fringes (potentially Ar-free) strongly increases the apparent age differences among crystallites of different size.

The importance of different frequency bands in predicting subcutaneous glucose concentration in type 1 diabetic patients.

PubMed

Lu, Yinghui; Gribok, Andrei V; Ward, W Kenneth; Reifman, Jaques

2010-08-01

We investigated the relative importance and predictive power of different frequency bands of subcutaneous glucose signals for the short-term (0-50 min) forecasting of glucose concentrations in type 1 diabetic patients with data-driven autoregressive (AR) models. The study data consisted of minute-by-minute glucose signals collected from nine deidentified patients over a five-day period using continuous glucose monitoring devices. AR models were developed using single and pairwise combinations of frequency bands of the glucose signal and compared with a reference model including all bands. The results suggest that: for open-loop applications, there is no need to explicitly represent exogenous inputs, such as meals and insulin intake, in AR models; models based on a single-frequency band, with periods between 60-120 min and 150-500 min, yield good predictive power (error <3 mg/dL) for prediction horizons of up to 25 min; models based on pairs of bands produce predictions that are indistinguishable from those of the reference model as long as the 60-120 min period band is included; and AR models can be developed on signals of short length (approximately 300 min), i.e., ignoring long circadian rhythms, without any detriment in prediction accuracy. Together, these findings provide insights into efficient development of more effective and parsimonious data-driven models for short-term prediction of glucose concentrations in diabetic patients.

Detection of shallow buried objects using an autoregressive model on the ground penetrating radar signal

NASA Astrophysics Data System (ADS)

Nabelek, Daniel P.; Ho, K. C.

2013-06-01

The detection of shallow buried low-metal content objects using ground penetrating radar (GPR) is a challenging task. This is because these targets are right underneath the ground and the ground bounce reflection interferes with their detections. They do not create distinctive hyperbolic signatures as required by most existing GPR detection algorithms due to their special geometric shapes and low metal content. This paper proposes the use of the Autoregressive (AR) modeling method for the detection of these targets. We fit an A-scan of the GPR data to an AR model. It is found that the fitting error will be small when such a target is present and large when it is absent. The ratio of the energy in an Ascan before and after AR model fitting is used as the confidence value for detection. We also apply AR model fitting over scans and utilize the fitting residual energies over several scans to form a feature vector for improving the detections. Using the data collected from a government test site, the proposed method can improve the detection of this kind of targets by 30% compared to the pre-screener, at a false alarm rate of 0.002/m2.

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

NASA Astrophysics Data System (ADS)

Sudo, Masafumi; Altenberger, Uwe; Günter, Christina

2014-05-01

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

Synthesis and Evaluation of Phenylxanthine Derivatives as Potential Dual A2AR Antagonists/MAO-B Inhibitors for Parkinson's Disease.

PubMed

Wang, Xuebao; Han, Chao; Xu, Yong; Wu, Kaiqi; Chen, Shuangya; Hu, Mangsha; Wang, Luyao; Ye, Yun; Ye, Faqing

2017-06-17

The aim of this research was to prove the speculation that phenylxanthine (PX) derivatives possess adenosine A2A receptor (A2AR)-blocking properties and to screening and evaluate these PX derivatives as dual A2AR antagonists/MAO-B inhibitors for Parkinson's disease. To explore this hypothesis, two series of PX derivatives were prepared and their antagonism against A2AR and inhibition against MAO-B were determined in vitro. In order to evaluate further the antiparkinsonian properties, pharmacokinetic and haloperidol-induced catalepsy experiments were carried out in vivo. The PX-D and PX-E analogues acted as potent A2AR antagonists with Ki values ranging from 0.27 to 10 μM, and these analogues displayed relatively mild MAO-B inhibition potencies, with inhibitor dissociation constants (Ki values) ranging from 0.25 to 10 μM. Further, the compounds PX-D-P6 and PX-E-P8 displayed efficacious antiparkinsonian properties in haloperidol-induced catalepsy experiments, verifying that these two compounds were potent A2AR antagonists and MAO-B inhibitors. We conclude that PX-D and PX-E analogues are a promising candidate class of dual-acting compounds for treating Parkinson's disease.

An ion source for radiofrequency-pulsed glow discharge time-of-flight mass spectrometry

NASA Astrophysics Data System (ADS)

González Gago, C.; Lobo, L.; Pisonero, J.; Bordel, N.; Pereiro, R.; Sanz-Medel, A.

2012-10-01

A Grimm-type glow discharge (GD) has been designed and constructed as an ion source for pulsed radiofrequency GD spectrometry when coupled to an orthogonal time of flight mass spectrometer. Pulse shapes of argon species and analytes were studied as a function of the discharge conditions using a new in-house ion source (UNIOVI GD) and results have been compared with a previous design (PROTOTYPE GD). Different behavior and shapes of the pulse profiles have been observed for the two sources evaluated, particularly for the plasma gas ionic species detected. In the more analytically relevant region (afterglow), signals for 40Ar+ with this new design were negligible, while maximum intensity was reached earlier in time for 41(ArH)+ than when using the PROTOTYPE GD. Moreover, while maximum 40Ar+ signals measured along the pulse period were similar in both sources, 41(ArH)+ and 80(Ar2)+ signals tend to be noticeable higher using the PROTOTYPE chamber. The UNIOVI GD design was shown to be adequate for sensitive direct analysis of solid samples, offering linear calibration graphs and good crater shapes. Limits of detection (LODs) are in the same order of magnitude for both sources, although the UNIOVI source provides slightly better LODs for those analytes with masses slightly higher than 41(ArH)+.

A Pilot Study of Augmented Reality Technology Applied to the Acetabular Cup Placement During Total Hip Arthroplasty.

PubMed

Ogawa, Hiroyuki; Hasegawa, Seiichirou; Tsukada, Sachiyuki; Matsubara, Masaaki

2018-06-01

We developed an acetabular cup placement device, the AR-HIP system, using augmented reality (AR). The AR-HIP system allows the surgeon to view an acetabular cup image superimposed in the surgical field through a smartphone. The smartphone also shows the placement angle of the acetabular cup. This preliminary study was performed to assess the accuracy of the AR-HIP system for acetabular cup placement during total hip arthroplasty (THA). We prospectively measured the placement angles using both a goniometer and AR-HIP system in 56 hips of 54 patients undergoing primary THA. We randomly determined the order of intraoperative measurement using the 2 devices. At 3 months after THA, the placement angle of the acetabular cup was measured on computed tomography images. The primary outcome was the absolute value of the difference between intraoperative and postoperative computed tomography measurements. The measurement angle using AR-HIP was significantly more accurate in terms of radiographic anteversion than that using a goniometer (2.7° vs 6.8°, respectively; mean difference 4.1°; 95% confidence interval, 3.0-5.2; P < .0001). There was no statistically significant difference in terms of radiographic inclination (2.1° vs 2.6°; mean difference 0.5°; 95% confidence interval, -1.1 to 0.1; P = .13). In this pilot study, the AR-HIP system provided more accurate information regarding acetabular cup placement angle than the conventional method. Further studies are required to confirm the utility of the AR-HIP system as a navigation tool. Copyright © 2018 Elsevier Inc. All rights reserved.

A comparative study of capacitively coupled HBr/He, HBr/Ar plasmas for etching applications: Numerical investigation by fluid model

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

Gul, Banat, E-mail: banatgul@gmail.com; Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp; Aman-ur-Rehman, E-mail: amansadiq@gmail.com

Fluid model has been applied to perform a comparative study of hydrogen bromide (HBr)/He and HBr/Ar capacitively coupled plasma discharges that are being used for anisotropic etching process. This model has been used to identify the most dominant species in HBr based plasmas. Our simulation results show that the neutral species like H and Br, which are the key player in chemical etching, have bell shape distribution, while ions like HBr{sup +}, Br{sup +}, which play a dominant rule in the physical etching, have double humped distribution and show peaks near electrodes. It was found that the dilution of HBrmore » by Ar and/or He results in an increase in electron density and electron temperature, which results in more ionization and dissociation and hence higher densities of neutral and charged species can be achieved. The ratio of positive ion flux to the neutral flux increases with an increase in additive gas fraction. Compare to HBr/He plasma, the HBr/Ar plasma shows a maximum change in the ion density and flux and hence the etching rate can be considered in the ion-assisted and in the ion-flux etch regime in HBr/Ar discharge. The densities of electron and other dominant species in HBr/Ar plasma are higher than those of HBr/He plasma. The densities and fluxes of the active neutrals and positive ions for etching and subsequently chemical etching versus physical sputtering in HBr/Ar and HBr/He plasmas discharge can be controlled by tuning gas mixture ratio and the desire etching can be achieved.« less

Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons

PubMed Central

Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T.

2016-01-01

Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

An augmented reality tool for learning spatial anatomy on mobile devices.

PubMed

Jain, Nishant; Youngblood, Patricia; Hasel, Matthew; Srivastava, Sakti

2017-09-01

Augmented Realty (AR) offers a novel method of blending virtual and real anatomy for intuitive spatial learning. Our first aim in the study was to create a prototype AR tool for mobile devices. Our second aim was to complete a technical evaluation of our prototype AR tool focused on measuring the system's ability to accurately render digital content in the real world. We imported Computed Tomography (CT) data derived virtual surface models into a 3D Unity engine environment and implemented an AR algorithm to display these on mobile devices. We investigated the accuracy of the virtual renderings by comparing a physical cube with an identical virtual cube for dimensional accuracy. Our comparative study confirms that our AR tool renders 3D virtual objects with a high level of accuracy as evidenced by the degree of similarity between measurements of the dimensions of a virtual object (a cube) and the corresponding physical object. We developed an inexpensive and user-friendly prototype AR tool for mobile devices that creates highly accurate renderings. This prototype demonstrates an intuitive, portable, and integrated interface for spatial interaction with virtual anatomical specimens. Integrating this AR tool with a library of CT derived surface models provides a platform for spatial learning in the anatomy curriculum. The segmentation methodology implemented to optimize human CT data for mobile viewing can be extended to include anatomical variations and pathologies. The ability of this inexpensive educational platform to deliver a library of interactive, 3D models to students worldwide demonstrates its utility as a supplemental teaching tool that could greatly benefit anatomical instruction. Clin. Anat. 30:736-741, 2017. © 2017Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Extensive intestinal first-pass metabolism of arctigenin: evidenced by simultaneous monitoring of both parent drug and its major metabolites.

PubMed

Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

2014-03-01

The current study aims to investigate intestinal absorption and metabolism of arctigenin (AR) through simultaneous monitoring of AR and its major metabolites in rat plasma. An UPLC/MS/MS assay was developed with chromatographic separation of all analytes achieved by a C18 Column (3.9mm×150mm, 3.5μm) and a gradient elution with acetonitrile and 0.1% formic acid within 9min. Sample extraction with acetonitrile was optimized to achieve satisfactory recovery for both AR and its major metabolites. The lower limit of quantification (LLOQ) for all analytes was 25ng/ml. The intra-day and inter-day precision and accuracy of each analyte at LLOQ and three quality control (QC) concentrations (low, middle and high) in rat plasma was within 15.0% RSD and 15.0% bias. The extraction recoveries were within the range of 83.8-94.0% for all analytes. The developed and validated assay was then applied to the absorption study of AR in both Caco-2 cell monolayer model and in situ single-pass rat intestinal perfusion model. High absorption permeability of AR was demonstrated in both models with Papp of (1.76±0.48)×10(-5) (A→B) (Caco-2) and Pblood of (8.6±3.0)×10(-6)cm/s (intestinal perfusion). Extensive first-pass metabolism of AR to arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was identified in rat intestinal perfusion study with Cummins's extraction ratios of 0.458±0.012 and 0.085±0.013, respectively. The current assay method demonstrated to be a practical tool for pharmacokinetics investigation of AR with complicated metabolism pathways and multiple metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

PubMed

Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

2015-03-01

Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

Predicting the Pathogenicity of Aminoacyl-tRNA Synthetase Mutations

PubMed Central

Oprescu, Stephanie N.; Griffin, Laurie B.; Beg, Asim A.; Antonellis, Anthony

2016-01-01

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for charging tRNA with cognate amino acids—the first step in protein synthesis. ARSs are required for protein translation in the cytoplasm and mitochondria of all cells. Surprisingly, mutations in 28 of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data sustains that impaired enzyme function is a robust predictor of the pathogenicity of ARS mutations. However, experimental model systems that distinguish between pathogenic and non-pathogenic ARS variants are required for implicating newly identified ARS mutations in disease. Here, we outline strategies to assist in predicting the pathogenicity of ARS variants and urge cautious evaluation of genetic and functional data prior to linking an ARS mutation to a human disease phenotype. PMID:27876679

Kinetic Study of the Aroxyl-Radical-Scavenging Activity of Five Fatty Acid Esters and Six Carotenoids in Toluene Solution: Structure-Activity Relationship for the Hydrogen Abstraction Reaction.

PubMed

Mukai, Kazuo; Yoshimoto, Maya; Ishikura, Masaharu; Nagaoka, Shin-Ichi

2017-08-17

A kinetic study of the reaction between an aroxyl radical (ArO • ) and fatty acid esters (LHs 1-5, ethyl stearate 1, ethyl oleate 2, ethyl linoleate 3, ethyl linolenate 4, and ethyl arachidonate 5) has been undertaken. The second-order rate constants (k s ) for the reaction of ArO • with LHs 1-5 in toluene at 25.0 °C have been determined spectrophotometrically. The k s values obtained increased in the order of LH 1 < 2 < 3 < 4 < 5, that is, with increasing the number of double bonds included in LHs 1-5. The k s value for LH 5 was 2.93 × 10 -3 M -1 s -1 . From the result, it has been clarified that the reaction of ArO • with LHs 1-5 was explained by an allylic hydrogen abstraction reaction. A similar kinetic study was performed for the reaction of ArO • with six carotenoids (Car-Hs 1-6, astaxanthin 1, β-carotene 2, lycopene 3, capsanthin 4, zeaxanthin 5, and lutein 6). The k s values obtained increased in the order of Car-H 1 < 2 < 3 < 4 < 5 < 6. The k s value for Car-H 6 was 8.4 × 10 -4 M -1 s -1 . The k s values obtained for Car-Hs 1-6 are in the same order as that of the values for LHs 1-5. The results of detailed analyses of the k s values for the above reaction indicated that the reaction was also explained by an allylic hydrogen abstraction reaction. Furthermore, the structure-activity relationship for the reaction was discussed by taking the result of density functional theory calculation reported by Martinez and Barbosa into account.

Processing on weak electric signals by the autoregressive model

NASA Astrophysics Data System (ADS)

Ding, Jinli; Zhao, Jiayin; Wang, Lanzhou; Li, Qiao

2008-10-01

A model of the autoregressive model of weak electric signals in two plants was set up for the first time. The result of the AR model to forecast 10 values of the weak electric signals is well. It will construct a standard set of the AR model coefficient of the plant electric signal and the environmental factor, and can be used as the preferences for the intelligent autocontrol system based on the adaptive characteristic of plants to achieve the energy saving on agricultural productions.

Utilization of ICU Data to Improve 30 and 60 Day Mortality Models

DTIC Science & Technology

2017-01-06

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary Differential...short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an individual may experience the...hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in Maciàă I Garau et al., 2011). For acute

Inhibition of androgen receptor and β-catenin activity in prostate cancer

PubMed Central

Lee, Eugine; Madar, Aviv; David, Gregory; Garabedian, Michael J.; DasGupta, Ramanuj; Logan, Susan K.

2013-01-01

Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective approach to treating prostate cancer. Here we provide proof-of-concept that a small-molecule inhibitor of nuclear β-catenin activity (called C3) can inhibit both the AR and β-catenin–signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both β-catenin/T-cell factor and β-catenin/AR protein interaction, reflecting the fact that T-cell factor and AR have overlapping binding sites on β-catenin. Given that AR interacts with, and is transcriptionally regulated by β-catenin, C3 treatment also resulted in decreased occupancy of β-catenin on the AR promoter and diminished AR and AR/β-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and β-catenin cofactor, coactivator-associated arginine methyltransferase 1 (CARM1), providing insight into the unrecognized function of β-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model and blocked renewal of bicalutamide-resistant sphere-forming cells, indicating the therapeutic potential of this approach. PMID:24019458

Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer

PubMed Central

Narizhneva, Natalia V.; Tararova, Natalia D.; Ryabokon, Petro; Shyshynova, Inna; Prokvolit, Anatoly; Komarov, Pavel G.; Purmal, Andrei A.; Gudkov, Andrei V.; Gurova, Katerina V.

2010-01-01

In prostate cancer (PCa) patients, initial responsiveness to androgen deprivation therapy is frequently followed by relapse due to development of treatment-resistant androgen-independent PCa. This is typically associated with acquisition of mutations in AR that allow activity as a transcription factor in the absence of ligand, indicating that androgen-independent PCa remains dependent on AR function. Our strategy to effectively target AR in androgen-independent PCa involved using a cell-based readout to isolate small molecules that inhibit AR transactivation function through mechanisms other than modulation of ligand binding. A number of the identified inhibitors were toxic to AR-expressing PCa cells regardless of their androgen dependence. Among these, some only suppressed PCa cell growth (ARTIS), while others induced cell death (ARTIK). ARTIK, but not ARTIS, compounds caused disappearance of AR protein from treated cells. siRNA against AR behaved like ARTIK compounds, while a dominant negative AR mutant that prevents AR-mediated transactivation but does not eliminate the protein showed only a growth suppressive effect. These observations reveal a transcription-independent function of AR that is essential for PCa cell viability and, therefore, is an ideal target for anti-PCa treatment. Indeed, several of the identified AR inhibitors demonstrated in vivo efficacy in mouse models of PCa and are candidates for pharmacologic optimization. PMID:19946220

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

PubMed

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

2010-01-15

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

Chronology and petrogenesis of a 1.8 g lunar granitic clast:14321,1062

NASA Technical Reports Server (NTRS)

Shih, C.-Y.; Bansal, B. M.; Wiesmann, H.; Nyquist, L. E.; Bogard, D. D.; Wooden, J. L.

1985-01-01

Geochronological, isotopic, and trace element data for a pristine granite clast from Apollo 14 breccia 14321 obtained using Rb-Sr, Sm-Nd, and (Ar-39)-(Ar-40) methods are presented. Trace element data for a possibly related evolved rock, the quartz-monodiorite clast from breccia 15404 are also presented, and the relationship between these two rock types is discussed. The concordancy of the Rb-Sr and Sm-Nd internal isochron ages and especially the Rb-Sr model age strongly suggest that the granite clast formed 4.1 AE ago. It probably crystallized slowly in the crust and was later excavated and brecciated about 3.88 AE ago, as indicated by the Ar-Ar age. A two-stage model involving crystal fractionation followed by silicate liquid immiscibility is proposed for the lunar granite genesis.

Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer

PubMed Central

Carver, Brett S; Chapinski, Caren; Wongvipat, John; Hieronymus, Haley; Chen, Yu; Chandarlapaty, Sarat; Arora, Vivek K; Le, Carl; Koutcher, Jason; Scher, Howard; Scardino, Peter T; Rosen, Neal; Sawyers, Charles L

2011-01-01

Summary Prostate cancer is characterized by its dependence on androgen receptor and frequent activation of PI3K signaling. We find that AR transcriptional output is decreased in human and murine tumors with PTEN deletion and that PI3K pathway inhibition activates AR signaling by relieving feedback inhibition of HER kinases. Similarly, AR inhibition activates AKT signaling by reducing levels of the AKT phosphatase PHLPP. Thus, these two oncogenic pathways cross-regulate each other by reciprocal feedback. Inhibition of one activates the other, thereby maintaining tumor cell survival. However, combined pharmacologic inhibition of PI3K and AR signaling caused near complete prostate cancer regressions in a Pten-deficient murine prostate cancer model and in human prostate cancer xenografts, indicating that both pathways coordinately support survival. Significance The two most frequently activated signaling pathways in prostate cancer are driven by AR and PI3K. Inhibitors of the PI3K pathway are in early clinical trials and AR inhibitors confer clinical responses in most patients. However, these inhibitors rarely induce tumor regression in preclinical models. Here we show that these pathways regulate each other by reciprocal negative feedback, such that inhibition of one activates the other. Therefore, tumor cells can adapt and survive when either single pathway is inhibited pharmacologically. Our demonstration of profound tumor regressions with combined pathway inhibition in preclinical prostate tumor models provides rationale for combination therapy in patients. PMID:21575859

Kepler AutoRegressive Planet Search

NASA Astrophysics Data System (ADS)

Caceres, Gabriel Antonio; Feigelson, Eric

2016-01-01

The Kepler AutoRegressive Planet Search (KARPS) project uses statistical methodology associated with autoregressive (AR) processes to model Kepler lightcurves in order to improve exoplanet transit detection in systems with high stellar variability. We also introduce a planet-search algorithm to detect transits in time-series residuals after application of the AR models. One of the main obstacles in detecting faint planetary transits is the intrinsic stellar variability of the host star. The variability displayed by many stars may have autoregressive properties, wherein later flux values are correlated with previous ones in some manner. Our analysis procedure consisting of three steps: pre-processing of the data to remove discontinuities, gaps and outliers; AR-type model selection and fitting; and transit signal search of the residuals using a new Transit Comb Filter (TCF) that replaces traditional box-finding algorithms. The analysis procedures of the project are applied to a portion of the publicly available Kepler light curve data for the full 4-year mission duration. Tests of the methods have been made on a subset of Kepler Objects of Interest (KOI) systems, classified both as planetary `candidates' and `false positives' by the Kepler Team, as well as a random sample of unclassified systems. We find that the ARMA-type modeling successfully reduces the stellar variability, by a factor of 10 or more in active stars and by smaller factors in more quiescent stars. A typical quiescent Kepler star has an interquartile range (IQR) of ~10 e-/sec, which may improve slightly after modeling, while those with IQR ranging from 20 to 50 e-/sec, have improvements from 20% up to 70%. High activity stars (IQR exceeding 100) markedly improve. A periodogram based on the TCF is constructed to concentrate the signal of these periodic spikes. When a periodic transit is found, the model is displayed on a standard period-folded averaged light curve. Our findings to date on real-data tests of the KARPS methodology will be discussed including confirmation of some Kepler Team `candidate' planets. We also present cases of new possible planetary signals.

Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor.

PubMed

Patki, Mugdha; Huang, Yanfang; Ratnam, Manohar

2016-07-22

It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen-induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co-expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone-independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).

PubMed

Olson, Brian M; Bradley, Eric S; Sawicki, Thomas; Zhong, Weixiong; Ranheim, Erik A; Bloom, Jordan E; Colluru, Viswa T; Johnson, Laura E; Rekoske, Brian T; Eickhoff, Jens C; McNeel, Douglas G

2017-05-01

The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Does the duration and time of sleep increase the risk of allergic rhinitis? Results of the 6-year nationwide Korea youth risk behavior web-based survey.

PubMed

Kwon, Jeoung A; Lee, Minjee; Yoo, Ki-Bong; Park, Eun-Cheol

2013-01-01

Allergic rhinitis (AR) is the most common chronic disorder in the pediatric population. Although several studies have investigated the correlation between AR and sleep-related issues, the association between the duration and time of sleep and AR has not been analyzed in long-term national data. This study investigated the relationship between sleep time and duration and AR risk in middle- and high-school students (adolescents aged 12-18). We analyzed national data from the Korea Youth Risk Behavior Web-based Survey by the Korea Centers for Disease Control and Prevention from 2007-2012. The sample size was 274,480, with an average response rate of 96.2%. Multivariate logistic regression analyses were conducted to determine the relationship between sleep and AR risk. Furthermore, to determine the best-fitted model among independent variables such as sleep duration, sleep time, and the combination of sleep duration and sleep time, we used Akaike Information Criteria (AIC) to compare models. A total of 43,337 boys and 41,665 girls reported a diagnosis of AR at baseline. The odds ratio increased with age and with higher education and economic status of the parents. Further, students in mid-sized and large cities had stronger relationships to AR than those in small cities. In both genders, AR was associated with depression and suicidal ideation. In the analysis of sleep duration and sleep time, the odds ratio increased in both genders when sleep duration was <7 hours, and when the time of sleep was later than 24:00 hours. Our results indicate an association between sleep time and duration and AR. This study is the first to focus on the relationship between sleep duration and time and AR in national survey data collected over 6 years.

Novel approaches for targeting the adenosine A2A receptor.

PubMed

Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

2015-01-01

The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

Noble Gases in Alpine Gold: U/Th-He Dating and Excesses of Radiogenic He and AR

NASA Astrophysics Data System (ADS)

Eugster, O.; Hofmann, B.; Krahenbuhl, U.; Neuenschwander, J.

1992-07-01

Gold precipitates in hydrothermal fluids along with other heavy elements, such as Ag and Pt. In order to explore the possibility of dating the formation of gold we determined the concentrations of U, Th, and their decay product ^4He, as well as the K and ^40Ar concentrations in vein-type gold and in placer gold samples. The gold-quartz veins at Brusson in the south-western alps were formed approximately 32 Ma ago during an episode of tectonic uplift (Diamond, 1990). Alpine material was deposited as sediment layers in the region of central Switzerland and placer gold is thus relatively abundant in the rivers of the Napf area. We washed placer gold from the river Grosse Fontanne in 1990 and 1991. Placer gold that had been collected from the river Kruempelgraben in 1933 and a sample of vein-type free gold grown on quartz rock from the Brusson area (Val d'Ayas) have been obtained from the Museum of Natural History in Bern. Table 1 gives the results. Most of the ^4He is released above 1050 degrees C, that is when gold melts, indicating that gold is extremely well retentive for He. From the ^4He concentration of (269 +- 20) x 10^-8 cm^3 STP/g, (0.4 +- 0.1) ppm U, and (0.9 +- 0.3) ppm Th for vein-type gold we calculate a U/Th-He age of (36 +- 8)Ma. This age agrees within errors with the proposed age of 32 Ma. The data given in Table 1 show that all placer gold samples contain excesses of radiogenic ^4He and ^40Ar relative to the concentrations expected from the U/Th and K decay, respectively, if we assume a formation age of 32 Ma. The quartz sample is depleted in ^4He but strongly enriched in radiogenic ^40Ar. The excess of ^40Ar(sub)rad is easier to explain than that of ^4He. Vein-type gold and placer gold contain quartz inclusions (Schmid, 1973). The high ^40Ar(sub)rad content of quartz (Table 1) indicates that the ^40Ar(sub)rad excess of gold originates from quartz inclusions. Excess ^4He in gold must be of radiogenic origin. Taking ^20Ne and ^36Ar as a measure for the quantity of trapped atmospheric noble gases we estimate atmospheric ^4He in the gold samples to be three to five orders of magnitude below the observed ^4He concentration. Placer gold is finely distributed in rock material and might be exposed to an alpha-particle irradiation from neighboring U/Th-rich minerals. An alternative He source are inclusions of U/Th-rich minerals, such as zircon, either within the gold material or mechanically worked into the spangles as they were part of the river detritus. Acknowledgement: We thank the Swiss NSF for their support. References: Diamond L.W. (1990) Am. J. of Science 290, 912-958. Schmid K. (1973) Schw. Min. Petr. Mitt. 53, 125-156. Table 1, which in the hard copy appears here, shows concentrations of He, Ne, and Ar (10^-8 cm^3 STP/g) and of K, Th, and U (ppm) in vein-type free gold, placer gold, and quartz. The ^3He and ^21Ne signals were below detection limits, that is ^4He/^3He in gold is >100'000. Average ^20Ne/^22Ne ratios in gold and quartz are 10.2 +- 0.2, that is about 4% larger than in the terrestrial atmosphere. Average ^36Ar/^38Ar = 5.2 +- 0.2 (within errors identical to ^36Ar/^38Ar in air). 1) Sample sizes 50-100 mg. 2) Radiogenic ^40Ar = ^40Ar-295.5 x ^36Ar. 3) Calculated from U/Th and ^40K decay.

Insights into arsenic multi-operons expression and resistance mechanisms in Rhodopseudomonas palustris CGA009

PubMed Central

Zhao, Chungui; Zhang, Yi; Chan, Zhuhua; Chen, Shicheng; Yang, Suping

2015-01-01

Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III)) concentrations (up to 1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase (55 h). ars2 operon was actively expressed even at the low concentration of As(III) (0.01 μM), whereas the ars3 operon was expressed at 1.0 μM of As(III), indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase). Arsenic speciation analysis demonstrated that R. palustris could reduce As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic reduction and methylating arsenic mechanism, while the latter might occur with the presence of higher concentrations of arsenic. PMID:26441915

Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4

PubMed Central

Maïssa, Nawal; Covarelli, Valentina; Janel, Sébastien; Durel, Beatrice; Simpson, Nandi; Bernard, Sandra C.; Pardo-Lopez, Liliana; Bouzinba-Ségard, Haniaa; Faure, Camille; Scott, Mark G.H.; Coureuil, Mathieu; Morand, Philippe C.; Lafont, Frank; Nassif, Xavier; Marullo, Stefano; Bourdoulous, Sandrine

2017-01-01

Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist haemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic receptor (β2AR), are sequentially engaged by meningococci to adhere and promote signalling events leading to vascular colonization, but their spatiotemporal coordination is unknown. Here we report that CD147 and β2AR form constitutive hetero-oligomeric complexes. The scaffolding protein α-actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147–β2AR complexes in highly ordered clusters at bacterial adhesion sites. This multimolecular assembly process increases the binding strength of meningococci to endothelial cells under shear stress, and creates molecular platforms for the elongation of membrane protrusions surrounding adherent bacteria. Thus, the specific organization of cellular receptors has major impacts on host–pathogen interaction. PMID:28569760

Overcoming mutation-based resistance to antiandrogens with rational drug design

PubMed Central

Balbas, Minna D; Evans, Michael J; Hosfield, David J; Wongvipat, John; Arora, Vivek K; Watson, Philip A; Chen, Yu; Greene, Geoffrey L; Shen, Yang; Sawyers, Charles L

2013-01-01

The second-generation antiandrogen enzalutamide was recently approved for patients with castration-resistant prostate cancer. Despite its success, the duration of response is often limited. For previous antiandrogens, one mechanism of resistance is mutation of the androgen receptor (AR). To prospectively identify AR mutations that might confer resistance to enzalutamide, we performed a reporter-based mutagenesis screen and identified a novel mutation, F876L, which converted enzalutamide into an AR agonist. Ectopic expression of AR F876L rescued the growth inhibition of enzalutamide treatment. Molecular dynamics simulations performed on antiandrogen–AR complexes suggested a mechanism by which the F876L substitution alleviates antagonism through repositioning of the coactivator recruiting helix 12. This model then provided the rationale for a focused chemical screen which, based on existing antiandrogen scaffolds, identified three novel compounds that effectively antagonized AR F876L (and AR WT) to suppress the growth of prostate cancer cells resistant to enzalutamide. DOI: http://dx.doi.org/10.7554/eLife.00499.001 PMID:23580326

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

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

Prewhitening of Colored Noise Fields for Detection of Threshold Sources

DTIC Science & Technology

1993-11-07

determines the noise covariance matrix, prewhitening techniques allow detection of threshold sources. The multiple signal classification ( MUSIC ...SUBJECT TERMS 1S. NUMBER OF PAGES AR Model, Colored Noise Field, Mixed Spectra Model, MUSIC , Noise Field, 52 Prewhitening, SNR, Standardized Test...EXAMPLE 2: COMPLEX AR COEFFICIENT .............................................. 5 EXAMPLE 3: MUSIC IN A COLORED BACKGROUND NOISE ...................... 6

Development of the ECLSS Sizing Analysis Tool and ARS Mass Balance Model Using Microsoft Excel

NASA Technical Reports Server (NTRS)

McGlothlin, E. P.; Yeh, H. Y.; Lin, C. H.

1999-01-01

The development of a Microsoft Excel-compatible Environmental Control and Life Support System (ECLSS) sizing analysis "tool" for conceptual design of Mars human exploration missions makes it possible for a user to choose a certain technology in the corresponding subsystem. This tool estimates the mass, volume, and power requirements of every technology in a subsystem and the system as a whole. Furthermore, to verify that a design sized by the ECLSS Sizing Tool meets the mission requirements and integrates properly, mass balance models that solve for component throughputs of such ECLSS systems as the Water Recovery System (WRS) and Air Revitalization System (ARS) must be developed. The ARS Mass Balance Model will be discussed in this paper.

Grafting of aniline derivatives onto chitosan and their applications for removal of reactive dyes from industrial effluents.

PubMed

Abbasian, Mojtaba; Jaymand, Mehdi; Niroomand, Pouneh; Farnoudian-Habibi, Amir; Karaj-Abad, Saber Ghasemi

2017-02-01

A series of chitosan-grafted polyaniline derivatives {chitosan-g-polyaniline (CS-g-PANI), chitosan-g-poly(N-methylaniline) (CS-g-PNMANI), and chitosan-g-poly(N-ethylaniline) (CS-g-PNEANI)} were synthesized by in situ chemical oxidation polymerization method. The synthesized copolymers were analyzed by means of Fourier transform infrared (FTIR), and ultraviolet-visible (UV-vis) spectroscopies, thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FE-SEM). These copolymers were applied as adsorbent for removal of acid red 4 (AR4) and direct red 23 (DR23) from aqueous solutions. The adsorption processes were optimized in terms of pH, adsorbent amount, and dyes concentrations. The maximum adsorption capacities (Q m ) for the synthesized copolymers were calculated, and among them the CS-g-PNEANI sample showed highest Q m for both AR4 (98mgg -1 ) and DR23 (112mgg -1 ) dyes. The adsorption kinetics of AR4 and DR23 dyes follow the pseudo-second order kinetic model. The regeneration and reusability tests revealed that the synthesized adsorbents had the relatively good reusability after five repetitions of the adsorption-desorption cycles. As the results, it is expected that the CS-g-PANIs find application for removal of reactive dyes (especially anionic dyes) from industrial effluents mainly due to their low production costs and high adsorption effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

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

The thermal evolution of Chinese central Tianshan and its implications: Insights from multi-method chronometry

NASA Astrophysics Data System (ADS)

Yin, Jiyuan; Chen, Wen; Hodges, Kip V.; Xiao, Wenjiao; Cai, Keda; Yuan, Chao; Sun, Min; Liu, Li-Ping; van Soest, Matthijs C.

2018-01-01

The Chinese Tianshan is located in the south of the Central Asian Orogenic Belt and formed during final consumption of the Paleo-Asian Ocean in the late Palaeozoic. In order to further elucidate the tectonic evolution of the Chinese Tianshan, we have established the temperature-time history of granitic rocks from the Chinese Tianshan through a multi-chronological approach that includes U/Pb (zircon), 40Ar/39Ar (biotite and K-feldspar), and (U-Th)/He (zircon and apatite) dating. Our data show that the central Tianshan experienced accelerated cooling during the late Carboniferous- to early Permian. Multiple sequences of complex multiple accretionary, subduction and collisional events could have induced the cooling in the Tianshan Orogenic Belt. The new 40Ar/39Ar and (U-Th)/He data, in combination with thermal history modeling results, reveal that several tectonic reactivation and exhumation episodes affected the Chinese central Tianshan during middle Triassic (245-210 Ma), early Cretaceous (140-100 Ma), late Oligocene-early Miocene (35-20 Ma) and late Miocene (12-9 Ma). The middle Triassic cooling dates was only found in the central Tianshan. Strong uplift and deformation in the Chinese Tianshan has been limited and localized. It have been concentrated in around major fault zone and the foreland thrust belt since the early Cretaceous. The middle Triassic and early Cretaceous exhumation is interpreted as distal effects of the Cimmerian collisions (i.e. the Qiangtang and Kunlun-Qaidam collision and Lhasa-Qiangtang collision) at the southern Eurasian margin. The Cenozoic reactivation and exhumation is interpreted as a far field response to the India-Eurasia collision and represents the beginning of modern mountain building and denudation in the Chinese Tianshan.

Age-dependent effects of esculetin on mood-related behavior and cognition from stressed mice are associated with restoring brain antioxidant status.

PubMed

Martín-Aragón, Sagrario; Villar, Ángel; Benedí, Juana

2016-02-04

Dietary antioxidants might exert an important role in the aging process by relieving oxidative damage, a likely cause of age-associated brain dysfunctions. This study aims to investigate the influence of esculetin (6,7-dihydroxycoumarin), a naturally occurring antioxidant in the diet, on mood-related behaviors and cognitive function and its relation with age and brain oxidative damage. Behavioral tests were employed in 11-, 17- and 22-month-old male C57BL/6J mice upon an oral 35day-esculetin treatment (25mg/kg). Activity of antioxidant enzymes, GSH and GSSG levels, GSH/GSSG ratio, and mitochondrial function were analyzed in brain cortex at the end of treatment in order to assess the oxidative status related to mouse behavior. Esculetin treatment attenuated the increased immobility time and enhanced the diminished climbing time in the forced swim task elicited by acute restraint stress (ARS) in the 11- and 17-month-old mice versus their counterpart controls. Furthermore, ARS caused an impairment of contextual memory in the step-through passive avoidance both in mature adult and aged mice which was partially reversed by esculetin only in the 11-month-old mice. Esculetin was effective to prevent the ARS-induced oxidative stress mostly in mature adult mice by restoring antioxidant enzyme activities, augmenting the GSH/GSSG ratio and increasing cytochrome c oxidase (COX) activity in cortex. Modulation of the mood-related behavior and cognitive function upon esculetin treatment in a mouse model of ARS depends on age and is partly due to the enhancement of redox status and levels of COX activity in cortex. Copyright © 2015. Published by Elsevier Inc.

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.

Insights into the mechanism of C5aR inhibition by PMX53 via implicit solvent molecular dynamics simulations and docking

PubMed Central

2014-01-01

Background The complement protein C5a acts by primarily binding and activating the G-protein coupled C5a receptor C5aR (CD88), and is implicated in many inflammatory diseases. The cyclic hexapeptide PMX53 (sequence Ace-Phe-[Orn-Pro-dCha-Trp-Arg]) is a full C5aR antagonist of nanomolar potency, and is widely used to study C5aR function in disease. Results We construct for the first time molecular models for the C5aR:PMX53 complex without the a priori use of experimental constraints, via a computational framework of molecular dynamics (MD) simulations, docking, conformational clustering and free energy filtering. The models agree with experimental data, and are used to propose important intermolecular interactions contributing to binding, and to develop a hypothesis for the mechanism of PMX53 antagonism. Conclusion This work forms the basis for the design of improved C5aR antagonists, as well as for atomic-detail mechanistic studies of complement activation and function. Our computational framework can be widely used to develop GPCR-ligand structural models in membrane environments, peptidomimetics and other chemical compounds with potential clinical use. PMID:25170421

Evaluation of Global Observations-Based Evapotranspiration Datasets and IPCC AR4 Simulations

NASA Technical Reports Server (NTRS)

Mueller, B.; Seneviratne, S. I.; Jimenez, C.; Corti, T.; Hirschi, M.; Balsamo, G.; Ciais, P.; Dirmeyer, P.; Fisher, J. B.; Guo, Z.;

Total Water Vapor Transport Observed in Twelve Atmospheric Rivers over the Northeastern Pacific Ocean Using Dropsondes

NASA Astrophysics Data System (ADS)

Ralph, F. M.; Iacobellis, S.; Neiman, P. J.; Cordeira, J. M.; Spackman, J. R.; Waliser, D. E.; Wick, G. A.; White, A. B.; Fairall, C. W.

2014-12-01

Demory et al (2013) recently showed that the global water cycle in climate models, including the magnitude of water vapor transport, is strongly influenced by the model's spatial resolution. The lack of offshore observations is noted as a serious limitation in determining the correct amount of transport. Due to the key role of atmospheric rivers (ARs) in determining the global distribution of water vapor, quantifying transport from ARs is a high priority. This forms a foundation of the CalWater-2 experiment aimed at sampling many ARs during 2014-2018. In February 2014, an "early-start" deployment of the NOAA G-IV research aircraft sampled 10 ARs over the northeast Pacific Ocean. On six of these flights, dropsondes were deployed in a line crossing the AR so as to robustly sample the total water vapor transport (TVT). The TVT is defined here as the sum of the vertically integrated horizontal water vapor transport (IVT) in the AR using a baseline that stretches from its warm southern (or eastern) edge to its cool northern (or western) edge. TVT includes both AR-parallel and AR-perpendicular transport. These data double the overall number of such cross-AR airborne samples suitable for calculating TVT. Analysis of TVT for these six new samples, in combination with the six previous samples from the preceding 16 years (from CalJet, WISPAR, and a Hawaii-based campaign), will be shown. A comparison will be made of the AR width and TVT determined using the well-established integrated water vapor (IWV) threshold of 2 cm, versus an IVT threshold of 250 kg m-1 s-1. Finally, the data from a well sampled case on 13 February 2014 (23 sondes with 75-100 km spacing) will be used to assess the sensitivity of TVT to dropsonde horizontal spacing and vertical resolution. This sensitivity analysis is of practical importance for the upcoming CalWater-2 field campaign where the G-IV will be used to sample many additional AR events, due to the relatively high cost of the dropsondes.

Optical plasma monitoring of Y-Ba-Cu-O rf sputter target transients

NASA Astrophysics Data System (ADS)

Klein, J. D.; Yen, A.

1989-12-01

The plasma emission spectra resulting from rf sputtering Y-Ba-Cu-O targets were observed as a function of sputter time. Although most lines of the observed spectra are not attributable to target species, peaks associated with each of the cation elements were resolved. The Ba and Cu peaks can be used as tracking indicators of process conditions. For example, switching from an O2/Ar sputter atmosphere to pure Ar enhanced the Ba peak much more than that associated with Cu. The emission spectra from a newly fabricated target exhibited a slow first-order transient response in seeking equilibrium with the rf plasma. The transient response of a previously sputtered target is also first order but has a much shorter time constant.

The Measurement of the Evaporation Residues Excitation Functions in the Fusion Reactions 144Sm (40Ar,xn) and 166Er(40Ar,xn)

NASA Astrophysics Data System (ADS)

Chernysheva, E. V.; Rodin, A. M.; Belozerov, A. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Itkis, M. G.; Novoselov, A. S.; Oganessian, Yu. Ts.; Salamatin, V. S.; Stepantsov, S. V.; Vedeneev, V. Yu.; Yukhimchuk, S. A.; Krupa, L.; Kliman, J.; Motycak, S.; Sivacek, I.

2015-06-01

The evaporation residues excitation functions for the reactions 40Ar+144Sm→184Hg and 40Ar+166Er→206Rn were measured at the energies below and above the Coulomb barrier (Elab=142-207 MeV) using a mass-separator MASHA. The experimental data were compared with theoretical calculations using a Channel Coupling Model. The influence of experimental beam energy spread on the excitation functions was taking into account. It was found that structure of xn-cross sections correlate strongly with the nuclear structure of colliding nuclei.

Webizing mobile augmented reality content

NASA Astrophysics Data System (ADS)

Ahn, Sangchul; Ko, Heedong; Yoo, Byounghyun

2014-01-01

This paper presents a content structure for building mobile augmented reality (AR) applications in HTML5 to achieve a clean separation of the mobile AR content and the application logic for scaling as on the Web. We propose that the content structure contains the physical world as well as virtual assets for mobile AR applications as document object model (DOM) elements and that their behaviour and user interactions are controlled through DOM events by representing objects and places with a uniform resource identifier. Our content structure enables mobile AR applications to be seamlessly developed as normal HTML documents under the current Web eco-system.

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

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit

Here, a process model was developed to determine the net energy ratio (NER) for production of pellets from steam pretreated agricultural residue (AR) and energy crop (i.e. switchgrass in this case). The NER is a ratio of the net energy output to the total net energy input from non-renewable energy sources into a system. Scenarios were developed to measure the effects of temperature and level of steam pretreatment on the NER of steam pretreated AR- and switch grass-based pellets. The NER for the base case at 6 kg h -1 is 1.76 and 1.37 for steam-pretreated AR- and switchgrass-based pellets,more » respectively. The reason behind the difference is that more energy is required to dry switchgrass pellets than AR pellets. The sensitivity analysis for the model shows that the optimum temperature for steam pretreatment is 160 C with 50% pretreatment (half the feedstock is pretreated, while the rest is undergoes regular pelletization). The uncertainty results for NER for steam pretreated AR and switch grass pellets are 1.62 ± 0.10 and 1.42 ± 0.11, respectively.« less

Structure-bias relationships for fenoterol stereoisomers in six molecular and cellular assays at the β2-adrenoceptor.

PubMed

Reinartz, Michael T; Kälble, Solveig; Littmann, Timo; Ozawa, Takeaki; Dove, Stefan; Kaever, Volkhard; Wainer, Irving W; Seifert, Roland

2015-01-01

Functional selectivity is well established as an underlying concept of ligand-specific signaling via G protein-coupled receptors (GPCRs). Functionally, selective drugs could show greater therapeutic efficacy and fewer adverse effects. Dual coupling of the β2-adrenoceptor (β2AR) triggers a signal transduction via Gsα and Giα proteins. Here, we examined 12 fenoterol stereoisomers in six molecular and cellular assays. Using β2AR-Gsα and β2AR-Giα fusion proteins, (R,S')- and (S,S')-isomers of 4'-methoxy-1-naphthyl-fenoterol were identified as biased ligands with preference for Gs. G protein-independent signaling via β-arrestin-2 was disfavored by these ligands. Isolated human neutrophils constituted an ex vivo model of β2AR signaling and demonstrated functional selectivity through the dissociation of cAMP accumulation and the inhibition of formyl peptide-stimulated production of reactive oxygen species. Ligand bias was calculated using an operational model of agonism and revealed that the fenoterol scaffold constitutes a promising lead structure for the development of Gs-biased β2AR agonists.

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.

Androgen Receptor Gene Polymorphisms and Alterations in Prostate Cancer: Of Humanized Mice and Men

PubMed Central

Robins, Diane M.

2011-01-01

Germline polymorphisms and somatic mutations of the androgen receptor (AR) have been intensely investigated in prostate cancer but even with genomic approaches their impact remains controversial. To assess the functional significance of AR genetic variation, we converted the mouse gene to the human sequence by germline recombination and engineered alleles to query the role of a polymorphic glutamine (Q) tract implicated in cancer risk. In a prostate cancer model, AR Q tract length influences progression and castration response. Mutation profiling in mice provides direct evidence that somatic AR variants are selected by therapy, a finding validated in human metastases from distinct treatment groups. Mutant ARs exploit multiple mechanisms to resist hormone ablation, including alterations in ligand specificity, target gene selectivity, chaperone interaction and nuclear localization. Regardless of their frequency, these variants permute normal function to reveal novel means to target wild type AR and its key interacting partners. PMID:21689727

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.

Planar defects as Ar traps in trioctahedral micas: A mechanism for increased Ar retentivity in phlogopite

NASA Astrophysics Data System (ADS)

Camacho, A.; Lee, J. K. W.; Fitz Gerald, J. D.; Zhao, J.; Abdu, Y. A.; Jenkins, D. M.; Hawthorne, F. C.; Kyser, T. K.; Creaser, R. A.; Armstrong, R.; Heaman, L. W.

2012-08-01

The effects of planar defects and composition on Ar mobility in trioctahedral micas have been investigated in samples from a small marble outcrop (∼500 m2) in the Frontenac Terrane, Grenville Province, Ontario. These micas crystallized during amphibolite-facies metamorphism at ∼1170 Ma and experienced a thermal pulse ∼100 Ma later at shallow crustal levels associated with the emplacement of plutons. 87Rb/86Sr ages of the phlogopites range from ∼950 to ∼1050 Ma, consistent with resetting during the later thermal event. The same phlogopites however, give 40Ar/39Ar ages between ∼950 and 1160 Ma, spanning the age range of the two thermal events. This result is intriguing because these micas have undergone the same thermal history and were not deformed after peak metamorphic conditions. In order to understand this phenomenon, the chemical, crystallographical, and microstructural nature of four mica samples has been characterized in detail using a wide range of analytical techniques. The scanning electron microscope (SEM), electron microprobe (EMP), and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) data show that the micas are chemically homogeneous (with the exception of Ba) and similar in composition. The Fourier transform infrared spectroscopy and Mossbauer results show that the M sites for three of the micas are dominated by divalent cations and the Fe3+/(Fe2++Fe3+) ratio for all four phlogopites ranges from 0.10 to 0.25. The stable-isotopic data for calcite indicate that this outcrop was not affected by hydrothermal fluids after peak metamorphism. No correlation between chemical composition and 87Rb/86Sr and 40Ar/39Ar age or between crystal size and 40Ar/39Ar age is observed. The only major difference among all of the micas was revealed through transmitted electron microscope (TEM), which shows that the older 1M micas contain significantly more layer stacking defects, associated with crystallization, than the younger micas. We propose that these defect structures, which are enclosed entirely within the mineral grain may serve as Ar traps and effectively increase the Ar retentivity of the mineral. As this phenomenon has not been previously documented in micas, this may have significant implications for the interpretation of 40Ar/39Ar ages of minerals which have similar defect structures.

Computational analysis of the effect of valvular regurgitation on ventricular mechanics using a 3D electromechanics model.

PubMed

Lim, Ki Moo; Hong, Seung-Bae; Lee, Byong Kwon; Shim, Eun Bo; Trayanova, Natalia

2015-03-01

Using a three-dimensional electromechanical model of the canine ventricles with dyssynchronous heart failure, we investigated the relationship between severity of valve regurgitation and ventricular mechanical responses. The results demonstrated that end-systolic tension in the septum and left ventricular free wall was significantly lower under the condition of mitral regurgitation (MR) than under aortic regurgitation (AR). Stroke work in AR was higher than that in MR. On the other hand, the difference in stroke volume between the two conditions was not significant, indicating that AR may cause worse pumping efficiency than MR in terms of consumed energy and performed work.

On current contribution to Fronsdal equations

NASA Astrophysics Data System (ADS)

Misuna, N. G.

2018-03-01

We explore a local form of second-order Vasiliev equations proposed in [arxiv:arXiv:1706.03718] and obtain an explicit expression for quadratic corrections to bosonic Fronsdal equations, generated by gauge-invariant higher-spin currents. Our analysis is performed for general phase factor, and for the case of parity-invariant theory we find the agreement with expressions for cubic vertices available in the literature. This provides an additional indication that local frame proposed in [arxiv:arXiv:1706.03718] is the proper one.

A Network Optimization Solution using SAS/OR Tools for the Department of the Army Branching Problem

DTIC Science & Technology

2010-02-18

OPTMODEL; NETFLOW ;Nodes;Arcs;ROTC; assignments;Basic Branches;Cadet Satisfaction; CLASSIFICATION: Unclassified This paper will demonstrate...implement a solution using the NETFLOW procedure and repeat that network solution using the OPTMODEL procedure. The OPTMODEL implementation will be...96.545599 M 1 AV AV IN EN FA AR 4 96.221521 M 1 IN IN MI EN MP AR 1 Figure 1, Supply: cadet data (5 of 2545) ordered by OMS PROC NETFLOW takes a

Modelling the ArH+ emission from the Crab nebula

NASA Astrophysics Data System (ADS)

Priestley, F. D.; Barlow, M. J.; Viti, S.

2017-12-01

We have performed combined photoionization and photodissociation region (PDR) modelling of a Crab nebula filament subjected to the synchrotron radiation from the central pulsar wind nebula, and to a high flux of charged particles; a greatly enhanced cosmic-ray ionization rate over the standard interstellar value, ζ0, is required to account for the lack of detected [C I] emission in published Herschel SPIRE FTS observations of the Crab nebula. The observed line surface brightness ratios of the OH+ and ArH+ transitions seen in the SPIRE FTS frequency range can only be explained with both a high cosmic-ray ionization rate and a reduced ArH+ dissociative recombination rate compared to that used by previous authors, although consistent with experimental upper limits. We find that the ArH+/OH+ line strengths and the observed H2 vibration-rotation emission can be reproduced by model filaments with nH = 2 × 104 cm-3, ζ = 107ζ0 and visual extinctions within the range found for dusty globules in the Crab nebula, although far-infrared emission from [O I] and [C II] is higher than the observational constraints. Models with nH = 1900 cm-3 underpredict the H2 surface brightness, but agree with the ArH+ and OH+ surface brightnesses and predict [O I] and [C II] line ratios consistent with observations. These models predict HeH+ rotational emission above detection thresholds, but consideration of the formation time-scale suggests that the abundance of this molecule in the Crab nebula should be lower than the equilibrium values obtained in our analysis.

Stochastic Models in the DORIS Position Time Series: Estimates from the IDS Contribution to the ITRF2014

NASA Astrophysics Data System (ADS)

Klos, A.; Bogusz, J.; Moreaux, G.

2017-12-01

This research focuses on the investigation of the deterministic and stochastic parts of the DORIS (Doppler Orbitography and Radiopositioning Integrated by Satellite) weekly coordinate time series from the IDS contribution to the ITRF2014A set of 90 stations was divided into three groups depending on when the data was collected at an individual station. To reliably describe the DORIS time series, we employed a mathematical model that included the long-term nonlinear signal, linear trend, seasonal oscillations (these three sum up to produce the Polynomial Trend Model) and a stochastic part, all being resolved with Maximum Likelihood Estimation (MLE). We proved that the values of the parameters delivered for DORIS data are strictly correlated with the time span of the observations, meaning that the most recent data are the most reliable ones. Not only did the seasonal amplitudes decrease over the years, but also, and most importantly, the noise level and its type changed significantly. We examined five different noise models to be applied to the stochastic part of the DORIS time series: a pure white noise (WN), a pure power-law noise (PL), a combination of white and power-law noise (WNPL), an autoregressive process of first order (AR(1)) and a Generalized Gauss Markov model (GGM). From our study it arises that the PL process may be chosen as the preferred one for most of the DORIS data. Moreover, the preferred noise model has changed through the years from AR(1) to pure PL with few stations characterized by a positive spectral index.

A robust damage-detection technique with environmental variability combining time-series models with principal components

NASA Astrophysics Data System (ADS)

Lakshmi, K.; Rama Mohan Rao, A.

2014-10-01

In this paper, a novel output-only damage-detection technique based on time-series models for structural health monitoring in the presence of environmental variability and measurement noise is presented. The large amount of data obtained in the form of time-history response is transformed using principal component analysis, in order to reduce the data size and thereby improve the computational efficiency of the proposed algorithm. The time instant of damage is obtained by fitting the acceleration time-history data from the structure using autoregressive (AR) and AR with exogenous inputs time-series prediction models. The probability density functions (PDFs) of damage features obtained from the variances of prediction errors corresponding to references and healthy current data are found to be shifting from each other due to the presence of various uncertainties such as environmental variability and measurement noise. Control limits using novelty index are obtained using the distances of the peaks of the PDF curves in healthy condition and used later for determining the current condition of the structure. Numerical simulation studies have been carried out using a simply supported beam and also validated using an experimental benchmark data corresponding to a three-storey-framed bookshelf structure proposed by Los Alamos National Laboratory. Studies carried out in this paper clearly indicate the efficiency of the proposed algorithm for damage detection in the presence of measurement noise and environmental variability.

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.

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

Comparative simulation analysis on the ignition threshold of atmospheric He and Ar dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Yao, Congwei; Chang, Zhengshi; Chen, Sile; Ma, Hengchi; Mu, Haibao; Zhang, Guan-Jun

2017-09-01

Dielectric barrier discharge (DBD) is widely applied in many fields, and the discharge characteristics of insert gas have been the research focus for years. In this paper, fluid models of atmospheric Ar and He DBDs driven by 22 kHz sinusoidal voltage are built to analyze their ignition processes. The contributions of different electron sources in ignition process are analyzed, including the direct ionization of ground state atom, stepwise ionization of metastable particles, and secondary electron emission from dielectric wall, and they play different roles in different discharge stages. The Townsend direct ionization coefficient of He is higher than Ar with the same electrical field intensity, which is the direct reason for the different ignition thresholds between He and Ar. Further, the electron energy loss per free electron produced in Ar and He DBDs is discussed. It is found that the total electron energy loss rate of Ar is higher than He when the same electrical field is applied. The excitation reaction of Ar consumes the major electron energy but cannot produce free electrons effectively, which is the essential reason for the higher ignition threshold of Ar. The computation results of He and Ar extinction voltages can be explained in the view of electron energy loss, as well as the experimental results of different extinction voltages between Ar/NH3 and He DBDs.

Impacts of an Anti-androgen and an Androgen/anti-androgen Mixture on the Metabolite Profile of Male Fathead Minnow Urine

EPA Science Inventory

Male and female fathead minnows (FHM) were exposed via the water to cyproterone acetate (CA), a model androgen receptor (AR) antagonist. FHM were also exposed to 517b-trenbolone (TB), a model AR agonist, and to mixtures of TB with CA. The urine metabolite profile of male FHM ex...

Effect of Ar{sup +} ion irradiation on the microstructure of pyrolytic carbon

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

Feng, Shanglei; Zhang, Dongsheng; Yang, Xinmei

2015-03-21

Pyrolytic carbon (PyC) coatings prepared by chemical vapor deposition were irradiated by 300 keV Ar{sup +} ions. Then, atomic force microscopy, synchrotron-based grazing incidence X-ray diffraction, Raman spectroscopy, X-ray photoemission spectroscopy, and transmission electron microscopy were employed to study how Ar{sup +} irradiation affects the microstructure of PyC, including the microstructural damage mechanisms and physics driving these phenomena. The 300 keV Ar{sup +} ion irradiation deteriorated the structure along the c-axis, which increased the interlayer spacing between graphene layers. With increasing irradiation dose, the density of defect states on the surface of PyC coating increases, and the basal planes gradually loses theirmore » initial ordering resulting in breaks in the lattice and turbulence at the peak damage dose reaches 1.58 displacement per atom (dpa). Surprisingly, the PyC becomes more textured as it becomes richer in structural defects with increasing irradiation dose.« less

Effect of different laser irradiation on the dysentery bacilli

NASA Astrophysics Data System (ADS)

Ou, Lin; Chen, Rong; Chen, Yanjiao; Li, Depin; Wen, Caixia

1998-08-01

The S. flexnesi, which have high drug-resistance especially in Cm, Sm, Tc, SD, were irradiated by Ar+ laser at 488 nm and semiconductor laser at 808 nm. The experiment results have shown that both Ar+ laser and semiconductor laser with power density of 1.7 w/cm2 and irradiation dose of 2000 J/cm2 can conduce to the bacterial lethality and increase the mutation rates of the bacterial drug-sensitivity, and 'Colony Count' method have the superiority over the 'Inhibacteria Ring' method. At the mean time it further indicate that the high power semiconductor laser would play an important role in the sciences of laser biological medicine. But the effect of the near infrared semiconductor laser is far lower than that of Ar+ laser of shorter wavelength at the same irradiation dose. It is clear that the output and irradiation dose of near infrared semiconductor laser shall be increased in order to get the same rates of the bacterial lethality and the drug-sensitivity mutation as Ar+ laser's.