Cellulose-Based Smart Fluids under Applied Electric Fields

PubMed Central

Choi, Kisuk; Gao, Chun Yan; Nam, Jae Do

2017-01-01

Cellulose particles, their derivatives and composites have special environmentally benign features and are abundant in nature with their various applications. This review paper introduces the essential properties of several types of cellulose and their derivatives obtained from various source materials, and their use in electro-responsive electrorheological (ER) suspensions, which are smart fluid systems that are actively responsive under applied electric fields, while, at zero electric field, ER fluids retain a liquid-like state. Given the actively controllable characteristics of cellulose-based smart ER fluids under an applied electric field regarding their rheological and dielectric properties, they can potentially be applied for various industrial devices including dampers and haptic devices. PMID:28891966

Spontaneous electrorheological effect in nematic liquid crystals under Taylor-Couette flow configuration

NASA Astrophysics Data System (ADS)

Dhar, Jayabrata; Chakraborty, Suman

2017-09-01

Electrorheological (ER) characteristics of Nematic Liquid Crystals (NLCs) have been a topic of immense interest in the field of soft matter physics owing to its rheological modulation capabilities. Here we explore the augmentation in rheological characteristics of the nematic fluid confined within the annular region of the concentric cylindrical space with an Electrical Double Layer (EDL) induced at the fluid-substrate interface due to certain physico-chemical interactions. Using a Taylor-Couette flow configuration associated with an EDL induced at the inner cylinder wall, we show that a spontaneous electrorheological effect is generated owing to the intrinsic director anisotropy and structural order of complex nematic fluids. We seek to find the enhancement in torque transfer capability due to the inherent electrorheological nature of the nematic medium, apart from exploiting the innate nature of such homogeneous media to remain free of coagulation, a fact which makes it an excellent candidate for the applications in microfluidic environment. Our analysis reveals that with stronger induced charge density within the EDL, the apparent viscosity enhances, which, in turn, augments torque transfer across the concentric cylinder. The velocity profile tends to flatten in comparison to the classical circular Couette flow in annular geometry as one increases the surface charge density. We further observe a more pronounced ER effect for the nematic medium having larger electrical permittivity anisotropy. Besides the torque transfer qualifications, we also explore the distinct scenarios, wherein the same NLC medium exhibits shear thinning and shear thickening characteristics. The present configuration of the efficient torque transfer mechanism may be proficiently downscaled to micro-level and is relevant in the fabrication of micro-clutch and micro-dampers.

Operational durability of a giant ER valve for Braille display

NASA Astrophysics Data System (ADS)

Luning, Xu; Han, Li; Yufei, Li; Shen, Rong; Kunquan, Lu

2017-05-01

The compact configuration of giant ER (electrorheological) valves provides the possibility of realizing a full-page Braille display. The operational durability of ER valves is a key issue in fulfilling a Braille display. A giant ER valve was used to investigate the variations in pressure drops and critical pressure drops of the valves over a long period under some typical operational parameters. The results indicate that neither the pressure drops nor critical pressure drops of giant ER valves show apparent deterioration over a long period. Without ER fluid exchange, a blockage appears in the channel of the valve because the ER structures induced by an external electric field cannot be broken by the Brownian motion of hydraulic oil molecules when the external electric field is removed. Forcing ER fluid flow is an effective and necessary method to keep the channel of the valve unblocked. Thus the operational durability of the valve using giant ER fluids is able to meet the demands of Braille display.

Quasi-steady Bingham plastic analysis of an electrorheological flow mode bypass damper with piston bleed

NASA Astrophysics Data System (ADS)

Lindler, Jason; Wereley, Norman M.

2003-06-01

We present an improved experimental validation of our nonlinear quasi-steady electrorheological (ER) and magnetorheological damper analysis, using an idealized Bingham plastic shear flow mechanism, for the flow mode of damper operation with leakage effect. To validate the model, a double-acting ER valve or bypass damper was designed and fabricated. Both the hydraulic cylinder and the bypass duct have cylindrical geometry, and damping forces are developed in the annular bypass via Poiseuille flow. The ER fluid damper contains a controlled amount of leakage around the piston head. The leakage allows ER fluid to flow from one side of the piston head to the opposite side without passing through the ER bypass. For this flow mode damper, the damping coefficient, defined as the ratio of equivalent viscous damping of the Bingham plastic material, Ceq, to the Newtonian viscous damping, C, is a function of the non-dimensional plug thickness only. The damper was tested for varying conditions of applied electric field and frequency using a mechanical damper dynamometer. In this analysis, the leakage damping coefficient with incorporated leakage effects, predict the amount of energy dissipated for a complete cycle of the piston rod. Measured force verses displacement cycles for multiple frequencies and electric fields validate the ability of the non-dimensional groups and the leakage damping coefficient to predict the damping levels for an ER bypass damper with leakage. Based on the experimental validation of the model using these data, the Bingham plastic analysis is shown to be an effective tool for the analysis-based design of double-acting ER bypass dampers.

ER fluid applications to vibration control devices and an adaptive neural-net controller

NASA Astrophysics Data System (ADS)

Morishita, Shin; Ura, Tamaki

1993-07-01

Four applications of electrorheological (ER) fluid to vibration control actuators and an adaptive neural-net control system suitable for the controller of ER actuators are described: a shock absorber system for automobiles, a squeeze film damper bearing for rotational machines, a dynamic damper for multidegree-of-freedom structures, and a vibration isolator. An adaptive neural-net control system composed of a forward model network for structural identification and a controller network is introduced for the control system of these ER actuators. As an example study of intelligent vibration control systems, an experiment was performed in which the ER dynamic damper was attached to a beam structure and controlled by the present neural-net controller so that the vibration in several modes of the beam was reduced with a single dynamic damper.

Synthesis and electrorheological characteristics of polyaniline/organoclay nanoparticles via Pickering emulsion polymerization

NASA Astrophysics Data System (ADS)

Fang, F. F.; Liu, Y. D.; Choi, H. J.

2010-12-01

Conducting polymer/inorganic composite particles have been regarded as a potential candidate material for electrorheological (ER) fluids when dispersed in non-conducting oils due to their synergistic physical properties such as enhanced thermal stability and high dielectric properties. In this study, we fabricated polyaniline (PANI)/clay nanoparticles with unique core-shell structure via Pickering emulsion in the phase of toluene by adopting exfoliated clay as a stabilizer. Successfully synthesized PANI nanospheres which were initialized by oil-soluble benzoyl peroxide possess a polydispersed size distribution of particles ranging from 200 nm to 1 µm. Surface morphology was revealed by SEM images in which some clay sheets were found to wrap the PANI nanoparticles compactly. TEM images explicitly confirm the position of exfoliated clay layers around the nanospheres. In addition, some nano-scaled particles showed an irregular shape because clay plates are difficult to bend while wrapping the very tiny PANI nanoparticles, so the x-ray diffraction (XRD) pattern did not indicate any obvious sharp peak, demonstrating the nearly completely exfoliated clay layers. Besides these, thermal gravimetric analysis (TGA) data also gave additional information on thermal stability and composition. Finally, the ER fluid was prepared by dispersing PANI/clay nanoparticles in silicone oil and the ER performance was investigated via a rotational rheometer under an applied electric field.

Viscous properties of aluminum oxide nanotubes and aluminium oxide nanoparticles - silicone oil suspensions

NASA Astrophysics Data System (ADS)

Thapa, Ram; French, Steven; Delgado, Adrian; Ramos, Carlos; Gutierrez, Jose; Chipara, Mircea; Lozano, Karen

2010-03-01

Electrorheological (ER) fluids consisting of γ-aluminum oxide nanotubes and γ-aluminum oxide nanoparticles dispersed within silicone oil were prepared. The relationship between shear stress and shear rate was measured and theoretically simulated by using an extended Bingham model for both the rheological and electrorheological features of these systems. Shear stress and viscosity showed a sharp increase for the aluminum oxide nanotubes suspensions subjected to applied electric fields whereas aluminum oxide nanoparticles suspensions showed a moderate change. It was found that the transition from liquid to solid state (mediated by the applied electric field) can be described by a power law and that for low applied voltages the relationship is almost linear.

Smart Fluid System Dually Responsive to Light and Electric Fields: An Electrophotorheological Fluid.

PubMed

Yoon, Chang-Min; Jang, Yoonsun; Noh, Jungchul; Kim, Jungwon; Jang, Jyongsik

2017-10-24

Electrophotorheological (EPR) fluids, whose rheological activity is dually responsive to light and electric fields (E fields), is formulated by mixing photosensitive spiropyran-decorated silica (SP-sSiO 2 ) nanoparticles with zwitterionic lecithin and mineral oil. A reversible photorheological (PR) activity of the EPR fluid is developed via the binding and releasing mechanism of lecithin and merocyanine (MC, a photoisomerized form of SP) under ultraviolet (UV) and visible (VIS) light applications. Moreover, the EPR fluid exhibits an 8-fold higher electrorheological (ER) performance compared to the SP-sSiO 2 nanoparticle-based ER fluid (without lecithin) under an E field, which is attributed to the enhanced dielectric properties facilitated by the binding of the lecithin and SP molecules. Upon dual application of UV light and an E field, the EPR fluid exhibits high EPR performance (ca. 115.3 Pa) that far exceeds its separate PR (ca. 0.8 Pa) and ER (ca. 57.5 Pa) activities, because of the synergistic contributions of the PR and ER effects through rigid and fully connected fibril-like structures. Consequently, this study offers a strategy on formulation of dual-stimuli responsive smart fluid systems.

Synthesis of kenaf cellulose carbamate and its smart electric stimuli-response.

PubMed

Gan, Sinyee; Piao, Shang Hao; Choi, Hyoung Jin; Zakaria, Sarani; Chia, Chin Hua

2016-02-10

Cellulose carbamate (CC) was produced from kenaf core pulp (KCP) via a microwave reactor-assisted method. The formation of CC was confirmed by Fourier transform infrared spectroscopy and nitrogen content analysis. The degree of substitution, zeta potential and size distribution of CC were also determined. The CC was characterized with scanning electron microscopy, X-ray diffraction and thermogravimetry analysis. The CC particles were then dispersed in silicone oil to prepare CC-based anhydrous electric stimuli-responsive electrorheological (ER) fluids. Rhelogical measurement was carried out using rotational rheometer with a high voltage generator in both steady and oscillatory shear modes to examine the effect of electric field strength on the ER characteristics. The results showed that the increase in electric field strength has enhanced the ER properties of CC-based ER fluid due to the chain formation induced by electric polarization among the particles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissipation of Energy in a Concentric ER Clutch and its Refined Quasi-Static Model

NASA Astrophysics Data System (ADS)

Oravský, Vladimír

A concentric electrorheological clutch (ERC) constituting the central part of a broader system: electro-hydro-aggregate (EHA) with an electrodrive (ED) on one side and a loading machine (brake B) on the other side is considered. The corresponding quasi-static model (at constant load and speed) is investigated and refined by insertion of power absorbed by electrorheological fluid (ERF). This increases the number of nondimensional parameters of the model from 8 to 12. Classification of several kinds of dissipation of energy in ERC is presented. Description and analysis of dissipation of the first kind are given more in detail and illustrated by synoptical diagrams. Also two definitions of efficiency of ERC are introduced and discussed.

PREFACE: 13th International Conference on Electrorheological Fluids and Magnetorheological Suspensions (ERMR2012)

NASA Astrophysics Data System (ADS)

Unal, Halil Ibrahim

2013-02-01

Conference photograph The 13th International Conference on Electrorheological Fluids and Magnetorheological Suspensions (ERMR2012) was held in Ankara, Turkey at Gazi University in the Architect Kemaleddin historical hall on 2-6 July 2012. The first International Conference on Electrorheological Fluids and Magnetorheological Suspensions took place nearly 25 years ago and this conference continued the same tradition by providing an arena for researchers around the world to present their new research findings in these fields, and gave them the opportunity to learn about the latest research and technology and to renew their acquaintances. The meeting brought together scientists and engineers in multidisciplinary areas such as chemical engineering, mechanical engineering, materials science and engineering, physics, chemistry and polymer science and technology, to explore the state-of-art technology, identify key areas to be focused on and discuss their problems/issues. All oral presentations were held in a single session to enhance the interactions between the scientists and engineers. The ERMR2012 Conference included plenary lectures given by prominent leaders in their respective fields. About 130 participants from more than 50 organizations attended the conference and 15 plenary speeches, 64 oral presentations and 57 poster presentations took place in the following areas: (i) synthesis, characterization and processing of novel ER/MR materials, (ii) dynamics, chain and structure formation of ER/MR materials, (iii) ER/MR elastomers, ferrogels and their characterizations, (iv) rheological techniques and measurements of ER/MR materials, (v) modeling and simulations of ER/MR materials, (vi) device development and control techniques and (vii) applications of ER/MR materials. The ERMR2012 International Conference began with Turkish classical music performed by the musicians of the Ministry of Culture and Tourism. Rector Professor Dr R Ayhan welcomed the participants and the conference chair Professor H I Unal delivered an opening talk before the plenary lectures. Magnetorheological (MR) materials and their applications featured prominently at the ERMR2012 Conference. C A Evrensel from the University of Nevada, USA, opened the first session with a plenary speech on 'Magnetorheological Fluids for Cancer Therapy'. In the field of magnetorheological elastomers (MRE), S Odenbach from TU Dresden, Germany highlighted new developments in data management which enable single particle analysis and statistical analysis of the structures in an MRE in his plenary lecture. Another plenary lecture in the MRE field was given by F Gordaninejad (University of Nevada, USA) on new developments for integrated systems with thick MREs. D Barber (LORD Corporation, USA) gave details of the latest developments of LORD® MR fluids at extremes in his plenary speech. R Hidalgo Alvarez from the University of Granada, Spain, focused on particle shape effects in MR fluids in his plenary talk. D J Klingenberg (University of Wisconsin, USA) illustrated how the increased extent of layer formation increases the yield stress by increasing the stresses transmitted by both the magnetizable and nonmagnetizable spheres in his plenary lecture. S Smoukov from Cambridge University, UK, demonstrated magnetically responsive bi-stable hierarchical materials with novel functionality, which can be effectively used to design sustainable and energy-responsive systems. J de Vicente from the University of Granada, Spain, highlighted true yield stress in magnetorheology with the aid of simulations and experimental techniques for a wide range of MR fluids, inverse ferrofluids and ionic liquids-based MR fluids in his plenary speech. H Böse (Fraunhofer Institute, Germany) gave his plenary speech on magnetorheological torque transmission devices with permanent magnets. W Li (University of Wollongong, Australia), M Nakano (Tohoku University, Japan) and S Xuan (University of Science and Technology of China) gave plenary talks on novel MR shear thickening fluids, MR rubber composites and MR plastomers, respectively. H J Choi (INHA University, Korea), X Zhao (Northwestern Polytechnical University, China) and R Tao (Temple University, USA) delivered plenary lectures on issues relating to the area of electrorheological (ER) fluids. In their talks, Choi and Zhao covered novel ER materials with core-shell structured microspheres and micro/nano hierarchical structured titania particles, respectively, and Tao focused on the reduction of the viscosity of liquid suspensions for energy applications in transporting crude oil via pipelines. Attendance of the presentations was exceptionally high. Poster presentations were divided into two sessions and held in the afternoons after the close of the sessions, which were filled with stimulating discussions. The award for the best student research in the area of electrorheological fluids, sponsored by the Winslow family, was given to Y D Liu of INHA University, Korea on research entitled 'Copolyaniline coated monodisperse polystyrene microparticles and their electrorheological response'. The award for the best student research on magnetorheological suspensions, sponsored by the LORD Corporation, was given to S Kaneko of Keio University, Japan on research entitled 'Effect of a magnetic field on sloshing pressure in a magnetic fluid'. Besides the purely scientific program during the five days, some special events were also organized. A guided tour of the old city and some important landmarks of the capital city of Ankara were organized before the Gala Dinner. Special samples of Turkish classical music and folk dancing were performed by a group from the Republic of Turkey Ministry of Culture and Tourism to exhibit Turkish culture to the delegates at Gala Night, which was truly appreciated. Following the conclusion of this successful meeting, the next conference is expected to be organized at the University of Granada, Spain by Professor F Gonzalez-Caballero in 2014. It is expected that during the next conference, the interaction between polymer chemists synthesizing the new ER/MR materials, experimentalists from the rheological side characterizing their rheological properties, theoretical physicists describing the electric field and magnetic field dependent phenomena in ER/MR fluids rheology, and mechanical engineers conducting vibration damping tests will give rise to a deeper understanding of the ER/MR phenomena and will result in new findings in this field. The conference was sponsored by Gazi University, Anton-Paar GmbH, Kurimoto Ltd., Anamed Analitik Grup, TA Instruments, LORD Corporation, Turkish Powder Metallurgy Association (TTMD), LiKrom Ltd, Atomika Ltd., Turkish Patent Institute (TPI), Berkecan Ltd., Kurukahveci Mehmed Efendi Mahdumlari and Turkish Science-Research Foundation (TUBAV). The organizing committee truly appreciates the support from these organizations. Special appreciation is also due to my students O Erol and H C Gullu. I would also like to thank members of the Local Organizing Committee and International Advisory Board. Guest Editor H Ibrahim Unal Gazi University Science Faculty Chemistry Department 06500 Ankara/Turkey E-mail: hiunal@gazi.edu.tr

Influence of Frequency-Dependent Dielectric Loss on Electrorheology of Surface Modified ZnO Nanofluids

NASA Astrophysics Data System (ADS)

Zaid, H. M.; Adil, M.; Lee, KC; Latiff, N. R. A.

2018-05-01

The shear dependent viscosity change in dielectric nanofluids under the applied electric field, provide potentials for prospect applications especially in enhanced oil recovery. When nanofluids are activated by an applied electric field, it behaves as a non-Newtonian fluid under electrorheological effect (ER) by creating the chains of nanoparticles. In this research, the effect of dielectric loss on the electrorheological characteristic of dielectric nanofluids (NFs) was studied, corresponding to the applied frequency of 167 and 18.8 MHz. For this purpose, electrorheological characteristics of ZnO (55.7 and 117.1 nm) nanofluids with various nanoparticles (NPs) concentration (0.1, 0.05, 0.01 wt. %) were measured. The measurement was done via solenoid based EM transmitter under salt water as a propagation medium. The result shows that the applied electric field caused an apparent increase on the relative viscosity of ZnO NFs due to electrorheological effect. However, the relative viscosity shows a higher increment at 167 MHz due to the greater dielectric loss, compared to 18.8 MHz. The high dielectric loss allows the dipole moments to rotationally polarize at the interfaces of nanoparticles, which create stronger chains that align with the applied electric field. Additionally, the relative viscosity demonstrated an increment with the increase in particle size of ZnO nanoparticles from 55.7 to 117.1 nm. While the viscosity of nanofluid also indicated the high dependence on particle loading.

Physics of field-responsive fluids

NASA Astrophysics Data System (ADS)

Wan, Tsz Kai Jones

Electrorheological (ER) fluid is a new class of material, which possesses a variety of potential applications, such as shock absorbers and clutches. It is formed by microparticles that are dispersed in a host fluid. The particles will form chains rapidly when we apply an electric field to the ER fluid. However, due to the inadequacy of knowledge, the proposed applications have not been commercialized yet. The prediction of the strength of the ER effect is the main concern in the theoretical investigation of ER fluids. The ER effect is originated from the induced interaction between the polarized particles in an ER fluid. Existing theories assume that the particles are at rest. In a realistic situation, the fluid flow exerts force and torque on the particles, setting the particles in both translational and rotational motions under these actions. Recent experiments showed that the induced forces between the rotating particles are markedly different from the values predicted by existing theories. To overcome the discrepancy between theory and experiment, we formulate a model to take the particle motion into account, and derive the dependence of forces on the angular velocity of the rotating particles. We develop first-principles methods to investigate the dynamic ER effects in which the suspended particles can have translational or rotational motions. A model based on the relaxation of polarization charge on the particle surfaces is proposed and solved for various experimental conditions. The method can be extended to study the ER effects of coated particles, crystalline particles, and to the magnetorheological effects of paramagnetic particles. Moreover, the nonlinear ER effects under a strong applied field will be studied by the same approach. The results may help in the preparation of materials for the design of ER fluids.

Influence of liquid phase on nanoparticle-based giant electrorheological fluid.

PubMed

Gong, Xiuqing; Wu, Jinbo; Huang, Xianxiang; Wen, Weijia; Sheng, Ping

2008-04-23

We show that the chemical structures of silicone oils can have an important role in the giant electrorheological (GER) effect. The interaction between silicone oils and solid nanoparticles is found to significantly influence the ER effect. By increasing the kinematic viscosity of silicone oils, which is a function of siloxane chain length, sol-like, gel-like and clay-like appearances of the constituted ER fluids were observed. Different functional-group-terminated silicone oils were also employed as the dispersing media. Significant differences of yield stress were found. We systematically study the effect of siloxane chain lengths on the permeability of oils traveling through the porous spaces between the particles (using the Washburn method), oils adsorbed on the particles' surface (using FT-IR spectra), as well as their particle size distribution (using dynamic light scattering). Our results indicate the hydrogen bonds are instrumental in linking the silicone oil to GER solid particles, and long chain lengths can enhance the agglomeration of the GER nanoparticles to form large clusters. An optimal oil structure, with hydroxyl-terminated silicone oil and a suitable viscosity, was chosen which can create the highest yield stress of ∼300 kPa under a 5 kV mm(-1) DC electric field.

Electrorheological fluids and methods

DOEpatents

Green, Peter F.; McIntyre, Ernest C.

2015-06-02

Electrorheological fluids and methods include changes in liquid-like materials that can flow like milk and subsequently form solid-like structures under applied electric fields; e.g., about 1 kV/mm. Such fluids can be used in various ways as smart suspensions, including uses in automotive, defense, and civil engineering applications. Electrorheological fluids and methods include one or more polar molecule substituted polyhedral silsesquioxanes (e.g., sulfonated polyhedral silsesquioxanes) and one or more oils (e.g., silicone oil), where the fluid can be subjected to an electric field.

a New ER Fluid Based Haptic Actuator System for Virtual Reality

NASA Astrophysics Data System (ADS)

Böse, H.; Baumann, M.; Monkman, G. J.; Egersdörfer, S.; Tunayar, A.; Freimuth, H.; Ermert, H.; Khaled, W.

The concept and some steps in the development of a new actuator system which enables the haptic perception of mechanically inhomogeneous virtual objects are introduced. The system consists of a two-dimensional planar array of actuator elements containing an electrorheological (ER) fluid. When a user presses his fingers onto the surface of the actuator array, he perceives locally variable resistance forces generated by vertical pistons which slide in the ER fluid through the gaps between electrode pairs. The voltage in each actuator element can be individually controlled by a novel sophisticated switching technology based on optoelectric gallium arsenide elements. The haptic information which is represented at the actuator array can be transferred from a corresponding sensor system based on ultrasonic elastography. The combined sensor-actuator system may serve as a technology platform for various applications in virtual reality, like telemedicine where the information on the consistency of tissue of a real patient is detected by the sensor part and recorded by the actuator part at a remote location.

Electrorheological suspensions of laponite in oil: rheometry studies.

PubMed

Parmar, K P S; Méheust, Y; Schjelderupsen, Børge; Fossum, J O

2008-03-04

We have studied the effect of an external direct current (DC) electric field ( approximately 1 kV/mm) on the rheological properties of colloidal suspensions consisting of aggregates of laponite particles in a silicone oil. Microscopy observations show that, under application of an electric field greater than a triggering electric field Ec approximately 0.6 kV/mm, laponite aggregates assemble into chain- and/or columnlike structures in the oil. Without an applied electric field, the steady-state shear behavior of such suspensions is Newtonian-like. Under application of an electric field larger than Ec, it changes dramatically as a result of the changes in the microstructure: a significant yield stress is measured, and under continuous shear the fluid is shear-thinning. The rheological properties, in particular the dynamic and static shear stress, were studied as a function of particle volume fraction for various strengths (including null) of the applied electric field. The flow curves at constant shear rate can be scaled with respect to both the particle fraction and electric field strength onto a master curve. This scaling is consistent with simple scaling arguments. The shape of the master curve accounts for the system's complexity; it approaches a standard power-law model at high Mason numbers. Both dynamic and static yield stresses are observed to depend on the particle fraction Phi and electric field E as PhibetaEalpha, with alpha approximately 1.85 and beta approximately 1 and 1.70 for the dynamic and static yield stresses, respectively. The yield stress was also determined as the critical stress at which there occurs a bifurcation in the rheological behavior of suspensions that are submitted to a constant shear stress; a scaling law with alpha approximately 1.84 and beta approximately 1.70 was obtained. The effectiveness of the latter technique confirms that such electrorheological (ER) fluids can be studied in the framework of thixotropic fluids. The method is very reproducible; we suggest that it could be used routinely for studying ER fluids. The measured overall yield stress behavior of the suspensions may be explained in terms of standard conduction models for electrorheological systems. Interesting prospects include using such systems for guided self-assembly of clay nanoparticles.

Electrohydrodynamic fibrillation governed enhanced thermal transport in dielectric colloids under a field stimulus.

PubMed

Dhar, Purbarun; Maganti, Lakshmi Sirisha; Harikrishnan, A R

2018-05-30

Electrorheological (ER) fluids are known to exhibit enhanced viscous effects under an electric field stimulus. The present article reports the hitherto unreported phenomenon of greatly enhanced thermal conductivity in such electro-active colloidal dispersions in the presence of an externally applied electric field. Typical ER fluids are synthesized employing dielectric fluids and nanoparticles and experiments are performed employing an in-house designed setup. Greatly augmented thermal conductivity under a field's influence was observed. Enhanced thermal conduction along the fibril structures under the field effect is theorized as the crux of the mechanism. The formation of fibril structures has also been experimentally verified employing microscopy. Based on classical models for ER fluids, a mathematical formalism has been developed to predict the propensity of chain formation and statistically feasible chain dynamics at given Mason numbers. Further, a thermal resistance network model is employed to computationally predict the enhanced thermal conduction across the fibrillary colloid microstructure. Good agreement between the mathematical model and the experimental observations is achieved. The domineering role of thermal conductivity over relative permittivity has been shown by proposing a modified Hashin-Shtrikman (HS) formalism. The findings have implications towards better physical understanding and design of ER fluids from both 'smart' viscoelastic as well as thermally active materials points of view.

The electrorheological behavior of suspensions based on molten-salt synthesized lithium titanate nanoparticles and their core-shell titanate/urea analogues.

PubMed

Plachy, T; Mrlik, M; Kozakova, Z; Suly, P; Sedlacik, M; Pavlinek, V; Kuritka, I

2015-02-18

This paper concerns the preparation of novel electrorheological (ER) materials using microwave-assisted synthesis as well as utilizing a suitable shell-providing system with enhanced ER performance. Lithium titanate nanoparticles were successfully synthesized, and their composition was confirmed via X-ray diffraction. Rheological properties were investigated in the absence as well as in the presence of an external electric field. Dielectric properties clarified the response of the particles to the application of an electric field. The urea-coated lithium titanate nanoparticle-based suspension exhibits higher ER performance in comparison to suspensions based on bare particles.

Method and device for producing a tactile display using an electrorheological fluid

NASA Technical Reports Server (NTRS)

Garner, H. Douglas (Inventor)

1996-01-01

A tactile display device utilizes an electrorheological fluid to activate a plurality of tactile dots. A voltage is selectively produced uniformly across an electrorheological fluid flowing between a common ground electrode and a plurality of conductive dot electrodes, thereby producing an increase in the fluid's viscosity to the extent that fluid flow between the two electrodes is restricted. The flow restriction produces a build-up of electrorheological fluid in a corresponding dot actuator chamber. The resulting pressure increase in the chamber displaces an elastic diaphragm fixed to a display surface to form a lump which can be perceived by the reader as one dot in a Braille character cell. A flow regulation system provides a continually pressurized flow system and provides for free flow of the electrorheological fluid through the plurality of dot actuator chambers when they are not activated. The device is adaptable to printed circuit techniques and can simultaneously display tactile dots representative of a full page of Braille characters stored on a medium such as a tape cassette or to display tactile dots representative of non-Braille data appearing on a computer monitor or contained on another data storage medium. In an alternate embodiment, the elastic diaphragm drives a plurality of spring-loaded pins provided with positive stops to maintain consistent displacements of the pins in both their actuated and nonactuated positions.

Tactile display device using an electrorheological fluid

NASA Technical Reports Server (NTRS)

Garner, H. Douglas (Inventor)

1994-01-01

A tactile display device utilizes an electrorheological fluid to activate a plurality of tactile dots. A voltage is selectively produced uniformly across an electrorheological fluid flowing between a common ground electrode and a plurality of conductive dot electrodes, thereby producing an increase in the fluid's viscosity to the extent that fluid flow between the two electrodes is restricted. The flow restriction produces a build-up of electrorheological fluid in a corresponding dot actuator chamber. The resulting pressure increase in the chamber displaces an elastic diaphragm fixed to a display surface to form a lump which can be perceived by the reader as one dot in a Braille character cell. A flow regulation system provides a continually pressurized flow system and provides for free flow of the electrorheological fluid through the plurality of dot actuator chambers when they are not activated. The device is adaptable to printed circuit techniques and can simultaneously display tactile dots representative of a full page of Braille characters stored on a medium such as a tape cassette or to display tactile dots representative of non-Braille data appearing on a computer monitor or contained on another data storage medium. In an alternate embodiment, the elastic diaphragm drives a plurality of spring-loaded pins provided with positive stops to maintain consistent displacements of the pins in both their actuated and nonactuated positions.

Influence of a surface film on the particles on the electrorheological response

NASA Astrophysics Data System (ADS)

Wu, C. W.; Conrad, H.

1997-01-01

A conduction model is developed for the dc electrorheological (ER) response of highly conducting particles (e.g., metal particles) suspended in a weakly conducting oil. The numerical analyses show that a surface film with some conductivity is desired, but not a completely insulating film as previously proposed. Increasing the film conductivity leads to an increase in the ER yield stress. However, too high a conductivity will give an unacceptable level of current density. The film should also have an intermediate thickness. A small thickness increases the possibility of electrical breakdown in the film; too large a thickness decreases the ER effect. Good agreement exists between the yield stress and the current density predicted by our model and those measured.

Multi-coated spheres: recommended electrorheological particles

NASA Astrophysics Data System (ADS)

Wu, C. W.; Conrad, H.

1998-11-01

This paper considers the design of electrorheological (ER) particles. Multi-coated particles suspended in insulating (very weakly conducting) oil are recommended for obtaining high-performance ER suspensions. Only the outer two coatings determine the ER strength. The outermost coating should be a material with high dielectric constant, high electrical breakdown strength and a reasonable level of conductivity. The coating immediately below should be a highly conducting material. The inner coatings, including the core (which can be void), can be of any material having such a density that the composite particle has substantially the same density as the host liquid. Our analysis gives that multi-coated particles can have an ER shear strength as high as 29 kPa when the volume fraction of particles is 0.4 and the applied field is 5 kV 0022-3727/31/22/021/img5. Results in the literature provide support for the concept and analysis.

Fully Soft 3D-Printed Electroactive Fluidic Valve for Soft Hydraulic Robots.

PubMed

Zatopa, Alex; Walker, Steph; Menguc, Yigit

2018-06-01

Soft robots are designed to utilize their compliance and contortionistic abilities to both interact safely with their environment and move through it in ways a rigid robot cannot. To more completely achieve this, the robot should be made of as many soft components as possible. Here we present a completely soft hydraulic control valve consisting of a 3D-printed photopolymer body with electrorheological (ER) fluid as a working fluid and gallium-indium-tin liquid metal alloy as electrodes. This soft 3D-printed ER valve weighs less than 10 g and allows for onboard actuation control, furthering the goal of an entirely soft controllable robot. The soft ER valve pressure-holding capabilities were tested under unstrained conditions, cyclic valve activation, and the strained conditions of bending, twisting, stretching, and indentation. It was found that the max holding pressure of the valve when 5 kV was applied across the electrodes was 264 kPa, and that the holding pressure deviated less than 15% from the unstrained max holding pressure under all strain conditions except for indentation, which had a 60% max pressure increase. In addition, a soft octopus-like robot was designed, 3D printed, and assembled, and a soft ER valve was used to stop the fluid flow, build pressure in the robot, and actuate six tentacle-like soft bending actuators.

Electrorheological effect and electro-optical properties of side-on liquid crystalline polysiloxane in a nematic solvent.

PubMed

Kaneko, Kosuke; Oto, Kodai; Kawai, Toshiaki; Choi, Hyunseok; Kikuchi, Hirotsugu; Nakamura, Naotake

2013-08-26

The electrorheological (ER) effect and the electro-optical properties of a ''side-on'' liquid crystalline polysiloxane (PS) are investigated. A large ER effect is observed and the response to the shear stress of neat PS in the nematic phase is shown to be affected by the shear rate. PS is also mixed with a low-molar nematic liquid crystal (5CB) in order to improve the response behavior to the applied electric field. The rheological properties of such mixtures are highly dependent on the concentration of 5CB. The composites respond faster to the applied electric field and have improved electro-optical properties. This study offers a new perspective on the development of liquid crystal materials for the ER effect. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control of an ER haptic master in a virtual slave environment for minimally invasive surgery applications

NASA Astrophysics Data System (ADS)

Han, Young-Min; Choi, Seung-Bok

2008-12-01

This paper presents the control performance of an electrorheological (ER) fluid-based haptic master device connected to a virtual slave environment that can be used for minimally invasive surgery (MIS). An already developed haptic joint featuring controllable ER fluid and a spherical joint mechanism is adopted for the master system. Medical forceps and an angular position measuring device are devised and integrated with the joint to establish the MIS master system. In order to embody a human organ in virtual space, a volumetric deformable object is used. The virtual object is then mathematically formulated by a shape-retaining chain-linked (S-chain) model. After evaluating the reflection force, computation time and compatibility with real-time control, the haptic architecture for MIS is established by incorporating the virtual slave with the master device so that the reflection force for the object of the virtual slave and the desired position for the master operator are transferred to each other. In order to achieve the desired force trajectories, a sliding mode controller is formulated and then experimentally realized. Tracking control performances for various force trajectories are evaluated and presented in the time domain.

Electrorheological crystallization of proteins and other molecules

DOEpatents

Craig, G.D.; Rupp, B.

1996-06-11

An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an X-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the X-ray diffraction pattern. 4 figs.

Electrorheological crystallization of proteins and other molecules

DOEpatents

Craig, George D.; Rupp, Bernhard

1996-01-01

An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an x-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the x-ray diffraction pattern.

New multifunction materials with both electrorheological performance and luminescence property

NASA Astrophysics Data System (ADS)

Chen, Ming-Xing; Shang, Yan-Li; Jia, Yun-Ling; Dong, Xiang-Yu; Ren, Jing; Li, Jun-Ran

2017-02-01

Novel multifunctional materials, the composites AlOOH-NaYFTb5 and AlOOH-NaYFTb10, containing AlO(OH) and β-NaYF4:5%Tb3+, have been synthesized via a facile hydrothermal route and a simple grinding method. The boehmite [AlO(OH)], yttrium nitrate [Y(NO3)3·6H2O], terbium nitrate, [Tb(NO3)3·6H2O], sodium citrate (Na3C6H5O7·2H2O) and sodium fluoride (NaF) were used as starting materials. The composition, electrorheological (ER) performance, and luminescence property of the functional materials were studied. Our results show that the composites not only have good electrorheological (ER) performance, but also have good optics property. The relative shear stress τ r ( τ r = τ E/ τ 0, τ E and τ 0 are the shear stresses at the electric field strength E = 4 and 0 kV/mm, respectively) values of the suspension (25 wt.%) of AlOOHNaYFTb5 material in silicone oil are all larger than 50 in a shear rate ranging from 0.06 to 26 s-1, the τr value reaches 1333 at a shear rate of 0.06 s-1. The material with such high ER activity and favorable luminescence performance is advantageous in its application as a multifunctional material.

Synthesis of flower-like BaTiO3/Fe3O4 hierarchically structured particles and their electrorheological and magnetic properties.

PubMed

Wang, Baoxiang; Yin, Yichao; Liu, Chenjie; Yu, Shoushan; Chen, Kezheng

2013-07-21

Flower-like BaTiO3/Fe3O4 hierarchically structured particles composed of nano-scale structures on micro-scale materials were synthesized by a simple solvothermal approach and characterized by the means of X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), magnetic testing and rotary viscometer. The influences on the morphology and structure of solvothermal times, type and amount of surfactant, EG : H2O ratio, etc. were studied. Magnetic testing results show that the samples have strong magnetism and they exhibit superparamagnetic behavior, as evidenced by no coercivity and the remanence at room temperature, due to their very small sizes, observed on the M-H loop. The saturation magnetization (M(s)) value can achieve 18.3 emu g(-1). The electrorheological (ER) effect was investigated using a suspension of the flower-like BaTiO3/Fe3O4 hierarchically structured particles dispersed in silicone oil. We can observe a slight shear-thinning behavior of shear viscosity at a low shear rate region even at zero applied electric field and a Newtonian fluid behavior at high shear rate regions.

The negative and positive electrorheological behavior and vibration damping characteristics of colemanite and polyindene/colemanite conducting composite

NASA Astrophysics Data System (ADS)

Cetin, B.; Unal, H. I.; Erol, O.

2012-12-01

In this study, the electrorheological (ER) properties of colemanite and polyindene (94.8% PIn)/colemanite (5.2%) conducting composite were investigated by dispersion in silicone oil (SO). The zeta (ζ)-potentials and antisedimentation ratios of the materials were determined. Some parameters which affect the ER properties of all the dispersions such as the volume fraction, electric field strength (E), shear rate, frequency and temperature were investigated. The rather unusual behavior known as the negative ER effect was observed for colemanite/SO above E = 1.5 kV mm-1 and for PIn/colemanite/SO under all values of the electric field strength even at high volume fraction. This negative ER response was converted to a positive one by the addition of non-ionic surfactant. Furthermore, glycerol was used as a polar promoter and observed to enhance the ER activity of the colemanite/SO system. Creep-recovery tests were applied to all the dispersions studied to investigate their behavior under sustained shear stress. Finally, 28% and 30% vibration damping capacities were achieved using an automobile shock absorber for the glycerol/colemanite/SO and non-ionic surfactant/PIn/colemanite/SO systems under the E = 0.17 kV mm-1 condition, respectively.

Yield Hardening of Electrorheological Fluids in Channel Flow

NASA Astrophysics Data System (ADS)

Helal, Ahmed; Qian, Bian; McKinley, Gareth H.; Hosoi, A. E.

2016-06-01

Electrorheological fluids offer potential for developing rapidly actuated hydraulic devices where shear forces or pressure-driven flow are present. In this study, the Bingham yield stress of electrorheological fluids with different particle volume fractions is investigated experimentally in wall-driven and pressure-driven flow modes using measurements in a parallel-plate rheometer and a microfluidic channel, respectively. A modified Krieger-Dougherty model can be used to describe the effects of the particle volume fraction on the yield stress and is in good agreement with the viscometric data. However, significant yield hardening in pressure-driven channel flow is observed and attributed to an increase and eventual saturation of the particle volume fraction in the channel. A phenomenological physical model linking the densification and consequent microstructure to the ratio of the particle aggregation time scale compared to the convective time scale is presented and used to predict the enhancement in yield stress in channel flow, enabling us to reconcile discrepancies in the literature between wall-driven and pressure-driven flows.

The electrorheological performance of polyaniline-based hybrid particles suspensions in silicone oil: influence of the dispersing medium viscosity

NASA Astrophysics Data System (ADS)

Roman, C.; García-Morales, M.; Goswami, S.; Marques, A. C.; Cidade, M. T.

2018-07-01

The potential of electrorheological (ER) suspensions based on polarizable particles in simple liquids relies on the particles arrangements which turn their quasi Newtonian behavior into gel-like. However, minor attention has been paid to the effect provoked by the liquid viscosity on the ease of orientation and assembly of the particles. With this aim, a study on the ER behavior, at 25 °C, of 1 wt% suspensions of polyaniline (PANI)-based hybrid particles (—graphene or —tungstene oxide) in silicone oil with varying viscosities (20, 50 and 100 cSt) was carried out. The electric field effect was higher for the PANI-graphene particles suspension in the less viscous silicone oil. However, two drawbacks were observed: (a) higher leakage current flows; and (b) reduced reversibility upon the electric field was turned off. The use of silicone oil with higher viscosity solved these issues.

Electrorheological fluid with an extraordinarily high yield stress

NASA Astrophysics Data System (ADS)

Zhang, Yuling; Lu, Kunquan; Rao, Guanghui; Tian, Yu; Zhang, Shaohua; Liang, Jingkui

2002-02-01

Surface modified complex strontium titanate microparticles are synthesized by means of a modified sol-gel technique. A suspension composed of these particles immersed in a silicone oil exhibits excellent electrorheological properties attractive to industry and technology applications: a yield stress as high as 27 kPa in an applied electric field of 3 kV/mm, a low leakage current, wide dynamic ranges in temperature and shear rate, and a long-term stability against sedimentation. In addition to the high dielectric constant of strontium titanate, surfactant and water-free character of the particles may be responsible for the dramatic improvement of the electrorheological properties of the suspension.

Electrorheological effect of Ti-bearing blast furnace slag with different TiC contents at 1500°C

NASA Astrophysics Data System (ADS)

Yue, Hong-rui; Jiang, Tao; Zhang, Qiao-yi; Duan, Pei-ning; Xue, Xiang-xin

2017-07-01

The electrorheological properties of CaO-SiO2-Al2O3-MgO-TiO2-TiC slags were investigated to enhance understanding of the effect of TiC addition on the viscosity, yield stress, and fluid pattern of Ti-bearing slags in a direct-current electric field. The viscosities and shear stresses of 4wt% and 8wt% TiC slags were found to increase substantially with increasing electric field intensity, whereas virtually no rheological changes were observed in the 0wt% TiC slag. The Herschel-Bulkley model was applied to demonstrate that the fluid pattern of the 4wt% TiC slag was converted from that of a Newtonian fluid to that of a Bingham fluid in response to the applied electric field; and the static yield stress increased linearly with the square of the electric field intensity.

Control of repulsive force in a virtual environment using an electrorheological haptic master for a surgical robot application

NASA Astrophysics Data System (ADS)

Oh, Jong-Seok; Choi, Seung-Hyun; Choi, Seung-Bok

2014-01-01

This paper presents control performances of a new type of four-degrees-of-freedom (4-DOF) haptic master that can be used for robot-assisted minimally invasive surgery (RMIS). By adopting a controllable electrorheological (ER) fluid, the function of the proposed master is realized as a haptic feedback as well as remote manipulation. In order to verify the efficacy of the proposed master and method, an experiment is conducted with deformable objects featuring human organs. Since the use of real human organs is difficult for control due to high cost and moral hazard, an excellent alternative method, the virtual reality environment, is used for control in this work. In order to embody a human organ in the virtual space, the experiment adopts a volumetric deformable object represented by a shape-retaining chain linked (S-chain) model which has salient properties such as fast and realistic deformation of elastic objects. In haptic architecture for RMIS, the desired torque/force and desired position originating from the object of the virtual slave and operator of the haptic master are transferred to each other. In order to achieve the desired torque/force trajectories, a sliding mode controller (SMC) which is known to be robust to uncertainties is designed and empirically implemented. Tracking control performances for various torque/force trajectories from the virtual slave are evaluated and presented in the time domain.

Stimuli-Responsive Polymer-Clay Nanocomposites under Electric Fields

PubMed Central

Piao, Shang Hao; Kwon, Seung Hyuk; Choi, Hyoung Jin

2016-01-01

This short Feature Article reviews electric stimuli-responsive polymer/clay nanocomposites with respect to their fabrication, physical characteristics and electrorheological (ER) behaviors under applied electric fields when dispersed in oil. Their structural characteristics, morphological features and thermal degradation behavior were examined by X-ray diffraction pattern, scanning electron microscopy and transmission electron microscopy, and thermogravimetric analysis, respectively. Particular focus is given to the electro-responsive ER characteristics of the polymer/clay nanocomposites in terms of the yield stress and viscoelastic properties along with their applications. PMID:28787852

Electrical and Electrorheological Properties of Alumina/Natural Rubber (STR XL) Composites

PubMed Central

Tangboriboon, Nuchnapa; Uttanawanit, Nuttapot; Longtong, Mean; Wongpinthong, Piraya; Sirivat, Anuvat; Kunanuruksapong, Ruksapong

2010-01-01

The electrorheological properties (ER) of natural rubber (XL)/alumina (Al2O3) composites were investigated in oscillatory shear mode under DC electrical field strengths between 0 to 2 kV/mm. SEM micrographs indicate a mean particle size of 9.873 ± 0.034 µm and particles that are moderately dispersed in the matrix. The XRD patterns indicate Al2O3 is of the β-phase polytype which possesses high ionic conductivity. The storage modulus (G′) of the composites, or the rigidity, increases by nearly two orders of magnitude, with variations in particle volume fraction and electrical field strength. The increase in the storage modulus is caused the ionic polarization of the alumina particles and the induced dipole moments set up in the natural rubber matrix.

Reconfigurable Full-Page Braille Displays

NASA Technical Reports Server (NTRS)

Garner, H. Douglas

1994-01-01

Electrically actuated braille display cells of proposed type arrayed together to form full-page braille displays. Like other braille display cells, these provide changeable patterns of bumps driven by digitally recorded text stored on magnetic tapes or in solid-state electronic memories. Proposed cells contain electrorheological fluid. Viscosity of such fluid increases in strong electrostatic field.

Shocking chocolate into shape

NASA Astrophysics Data System (ADS)

Ornes, Stephen

2016-11-01

Wouldn't you love chocolate to have less fat but all the taste? Stephen Ornes discovers how the study of electrorheological fluids has led one physicist to a develop a new way to trim the fat from chocolate

Self-assembly preparation of SiO2@Ni-Al layered double hydroxide composites and their enhanced electrorheological characteristics

PubMed Central

Ji, Xuqiang; Zhang, Wenling; Shan, Lei; Tian, Yu; Liu, Jingquan

2015-01-01

The core-shell structured SiO2@Ni-Al layered double hydroxide (LDH) composites were prepared via self-assembly of Ni-Al LDH on the surface of SiO2 spheres. Only coating a layer of ultrathin Ni-Al LDH sheet, the resulting SiO2@Ni-Al LDH composites exhibit significantly enhanced electrorheological (ER) characteristics compared to conventional bare SiO2 spheres. The monodispersed SiO2 spheres with average diameters of 260 nm were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS), while the shell part, Ni-Al LDH sheet was prepared by the hydrothermal procedure. The morphology of the samples was investigated via scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The structure of the samples was characterized by X-ray diffraction (XRD). The species and distribution of elements in samples were confirmed by X-ray photoelectron spectroscopy (XPS), Energy dispersive analysis of X-ray (EDX) and elemental mapping in STEM. Subsequently, the ER characteristics of the composites dispersed in insulating oil were characterized by a rotational rheometer. The electric field-stimulated rheological performances (yield stress, viscosity, modulus, etc.) were observed under an external electric field, which is different from the Newtonian state in the free electric field. PMID:26670467

Self-assembly preparation of SiO2@Ni-Al layered double hydroxide composites and their enhanced electrorheological characteristics

NASA Astrophysics Data System (ADS)

Ji, Xuqiang; Zhang, Wenling; Shan, Lei; Tian, Yu; Liu, Jingquan

2015-12-01

The core-shell structured SiO2@Ni-Al layered double hydroxide (LDH) composites were prepared via self-assembly of Ni-Al LDH on the surface of SiO2 spheres. Only coating a layer of ultrathin Ni-Al LDH sheet, the resulting SiO2@Ni-Al LDH composites exhibit significantly enhanced electrorheological (ER) characteristics compared to conventional bare SiO2 spheres. The monodispersed SiO2 spheres with average diameters of 260 nm were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS), while the shell part, Ni-Al LDH sheet was prepared by the hydrothermal procedure. The morphology of the samples was investigated via scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The structure of the samples was characterized by X-ray diffraction (XRD). The species and distribution of elements in samples were confirmed by X-ray photoelectron spectroscopy (XPS), Energy dispersive analysis of X-ray (EDX) and elemental mapping in STEM. Subsequently, the ER characteristics of the composites dispersed in insulating oil were characterized by a rotational rheometer. The electric field-stimulated rheological performances (yield stress, viscosity, modulus, etc.) were observed under an external electric field, which is different from the Newtonian state in the free electric field.

Control of electro-rheological fluid-based torque generation components for use in active rehabilitation devices

NASA Astrophysics Data System (ADS)

Nikitczuk, Jason; Weinberg, Brian; Mavroidis, Constantinos

2006-03-01

In this paper we present the design and control algorithms for novel electro-rheological fluid based torque generation elements that will be used to drive the joint of a new type of portable and controllable Active Knee Rehabilitation Orthotic Device (AKROD) for gait retraining in stroke patients. The AKROD is composed of straps and rigid components for attachment to the leg, with a central hinge mechanism where a gear system is connected. The key features of AKROD include: a compact, lightweight design with highly tunable torque capabilities through a variable damper component, full portability with on board power, control circuitry, and sensors (encoder and torque), and real-time capabilities for closed loop computer control for optimizing gait retraining. The variable damper component is achieved through an electro-rheological fluid (ERF) element that connects to the output of the gear system. Using the electrically controlled rheological properties of ERFs, compact brakes capable of supplying high resistive and controllable torques, are developed. A preliminary prototype for AKROD v.2 has been developed and tested in our laboratory. AKROD's v.2 ERF resistive actuator was tested in laboratory experiments using our custom made ERF Testing Apparatus (ETA). ETA provides a computer controlled environment to test ERF brakes and actuators in various conditions and scenarios including emulating the interaction between human muscles involved with the knee and AKROD's ERF actuators / brakes. In our preliminary results, AKROD's ERF resistive actuator was tested in closed loop torque control experiments. A hybrid (non-linear, adaptive) Proportional-Integral (PI) torque controller was implemented to achieve this goal.

Characterization and experimental validation of a squeeze film damper with MR fluid in a rotor-bearing system

NASA Astrophysics Data System (ADS)

Dominguez-Nuñez, L. A.; Silva-Navarro, G.

2014-04-01

The general study and applications of Magneto-Rhelogical (MR) dampers have been spread in the lasts years but only some studies have been focusing on the vibration control problems on rotor-bearings systems. Squeeze-Film Dampers (SFD) are now commonly used to passively control the vibration response on rotor-bearing systems because they can provide flexibility, damping and extend the so-called stability thresholds in rotating machinery. More recently, SFD are combined with MR or Electro-Rheological (ER) fluids to introduce a semiactive control mechanism to modify the rotordynamic coefficients and deal with the robust performance of the overall system response for higher operating speeds. There are, however, some theoretical and technological problems that complicate their extensive use, like the relationship between the centering spring flexibility and the rheological behavior of the smart fluid to produce the SFD forces. In this work it is considered a SFD with MR fluid and a set of circular section beams in a squirrel cage arrangement in combination with latex seals as centering springs. The mathematical model analysis includes the controllable viscoelastic properties associated to the MR fluid. The characterization of the SFD is made by the determination of some coefficients associated with a modified Choi-Lee-Park polynomial model. During the analysis is considered a rotor-bearing system modeled using finite element methods. The SFD with MR fluid is connected to an experimental platform to validate and experimentally evaluate the overall system. Finally, to improve the open-loop system performance, a methodology for the use of different control schemes is proposed.

Feedback control of an electrorheological long-stroke vibration damper

NASA Astrophysics Data System (ADS)

Sims, Neil D.; Stanway, Roger; Johnson, Andrew R.; Peel, David J.; Bullough, William A.

1999-06-01

It is widely acknowledged that the inherent non-linearity of smart fluid dampers is inhibiting the development of effective control regimes, and mass-production devices. In an earlier publication, an innovative solution to this problem was presented -- using a simple feedback control strategy to linearize the response. The study used a quasi-steady model of a long-stroke Electrorheological damper, and showed how proportional feedback control could linearize the simulated response. However, this initial research did not consider the dynamics of the damper's behavior, and so the development of a more advanced model has been necessary. In this article, the authors present an extension to this earlier study, using a model of the damper's response that is capable of accurately predicting the dynamic response of the damper. To introduce the topic, the electrorheological long-stroke damper test rig is described, and an overview of the earlier study is given. The advanced model is then derived, and its predictions are compared to experimental data from the test rig. This model is then incorporated into the feedback control simulations, and it is shown how the control strategy is still able to linearize the response in simulations.

Modeling and Design of an Electro-Rheological Fluid Based Haptic System for Tele-Operation of Space Robots

NASA Technical Reports Server (NTRS)

Mavroidis, Constantinos; Pfeiffer, Charles; Paljic, Alex; Celestino, James; Lennon, Jamie; Bar-Cohen, Yoseph

2000-01-01

For many years, the robotic community sought to develop robots that can eventually operate autonomously and eliminate the need for human operators. However, there is an increasing realization that there are some tasks that human can perform significantly better but, due to associated hazards, distance, physical limitations and other causes, only robot can be employed to perform these tasks. Remotely performing these types of tasks requires operating robots as human surrogates. While current "hand master" haptic systems are able to reproduce the feeling of rigid objects, they present great difficulties in emulating the feeling of remote/virtual stiffness. In addition, they tend to be heavy, cumbersome and usually they only allow limited operator workspace. In this paper a novel haptic interface is presented to enable human-operators to "feel" and intuitively mirror the stiffness/forces at remote/virtual sites enabling control of robots as human-surrogates. This haptic interface is intended to provide human operators intuitive feeling of the stiffness and forces at remote or virtual sites in support of space robots performing dexterous manipulation tasks (such as operating a wrench or a drill). Remote applications are referred to the control of actual robots whereas virtual applications are referred to simulated operations. The developed haptic interface will be applicable to IVA operated robotic EVA tasks to enhance human performance, extend crew capability and assure crew safety. The electrically controlled stiffness is obtained using constrained ElectroRheological Fluids (ERF), which changes its viscosity under electrical stimulation. Forces applied at the robot end-effector due to a compliant environment will be reflected to the user using this ERF device where a change in the system viscosity will occur proportionally to the force to be transmitted. In this paper, we will present the results of our modeling, simulation, and initial testing of such an electrorheological fluid (ERF) based haptic device.

The Rheological Behavior and Thixotropy of Electrorheological Suspensions in Differing Temperature/Velocity Conditions (Rheologicheskoe Povedenie i Tikostropiya Elektroreologicheskikh Suspenzii v Razlichnykh Temperaturno-Skorostnykh Rezhimakh)

DTIC Science & Technology

1990-10-29

unsuitable for ERS, the low water content (eg for aerosil and diatomite 1-3 wt%) being insufficient to activate them. The ERE starts to appear only beyond a...certain threshold water content adsorbed on the particles in suspension. With further increase in the quantity of adsorbed water the effective...silica-gel particles varies with varying water content In the silica suspensions examined the evidence of ERE was linked to the presence of adsorbed

A haptic sensor-actor-system based on ultrasound elastography and electrorheological fluids for virtual reality applications in medicine.

PubMed

Khaled, W; Ermert, H; Bruhns, O; Boese, H; Baumann, M; Monkman, G J; Egersdoerfer, S; Meier, A; Klein, D; Freimuth, H

2003-01-01

Mechanical properties of biological tissue represent important diagnostic information and are of histological relevance (hard lesions, "nodes" in organs: tumors; calcifications in vessels: arteriosclerosis). The problem is, that such information is usually obtained by digital palpation only, which is limited with respect to sensitivity. It requires intuitive assessment and does not allow quantitative documentation. A suitable sensor is required for quantitative detection of mechanical tissue properties. On the other hand, there is also some need for a realistic mechanical display of those tissue properties. Suitable actuator arrays with high spatial resolution and real-time capabilities are required operating in a haptic sensor actuator system with different applications. The sensor system uses real time ultrasonic elastography whereas the tactile actuator is based on electrorheological fluids. Due to their small size the actuator array elements have to be manufactured by micro-mechanical production methods. In order to supply the actuator elements with individual high voltages a sophisticated switching and control concept have been designed. This haptic system has the potential of inducing real time substantial forces, using a compact lightweight mechanism which can be applied to numerous areas including intraoperative navigation, telemedicine, teaching, space and telecommunication.

Electrorheological Fluid Based Force Feedback Device

NASA Technical Reports Server (NTRS)

Pfeiffer, Charles; Bar-Cohen, Yoseph; Mavroidis, Constantinos; Dolgin, Benjamin

1999-01-01

Parallel to the efforts to develop fully autonomous robots, it is increasingly being realized that there are applications where it is essential to have a fully controlled robot and "feel" its operating conditions, i.e. telepresence. This trend is a result of the increasing efforts to address tasks where humans can perform significantly better but, due to associated hazards, distance, physical limitations and other causes, only robots can be employed to perform these tasks. Such robots need to be assisted by a human that remotely controls the operation. To address the goal of operating robots as human surrogates, the authors launched a study of mechanisms that provide mechanical feedback. For this purpose, electrorheological fluids (ERF) are being investigated for the potential application as miniature haptic devices. This family of electroactive fluids has the property of changing the viscosity during electrical stimulation. Consequently, ERF can be used to produce force feedback haptic devices for tele-operated control of medical and space robotic systems. Forces applied at the robot end-effector due to a compliant environment are reflected to the user using an ERF device where a change in the system viscosity will occur proportionally to the transmitted force. Analytical model and control algorithms are being developed taking into account the non-linearities of these type of devices. This paper will describe the concept and the developed mechanism of ERF based force feedback. The test process and the physical properties of this device will be described and the results of preliminary tests will be presented.

Steering of SH wave propagation in electrorheological elastomer with a structured meta-slab by tunable phase discontinuities

NASA Astrophysics Data System (ADS)

Xu, Yanlong; Li, Yi; Cao, Liyun; Yang, Zhichun; Zhou, Xiaoling

2017-09-01

The generalized Snell's law (GSL) with phase discontinuity proposed based on the concept of a metasurface, which can be used to control arbitrarily the reflection and refraction of waves, attracts a growing attention in these years. The concept of abnormally deflecting the incident wave has been applied to the elastic field very recently. However, most of the studies on metasurfaces are based on passive materials, which restricts the frequency or the deflected angles always working in a single state. Here, we steer elastic SH wave propagation in an electrorheological (ER) elastomer with a structured meta-slab composed of geometrically periodic wave guides by exposing the slab to the programmed electric fields. The dependence of phase velocities of SH waves on the applied electric fields can make the phase shift under the form of a special function along the slab, which will control the refraction angles of the transmitted SH waves by the GSL. Accordingly we design the meta-slab theoretically and conduct corresponding numerical simulations. The results demonstrate that the structured meta-slab under the programmed external electric fields can deflect SH wave flexibly with tunable refraction angles and working frequencies, and can focus SH wave with tunable focal lengths. The present study will broaden the scope of applying adaptive materials to design metasurfaces with tunability.

The Response of Starch/gelatin/glycerin Aqueous Electrorheological Elastomer to Applied Electric Field

NASA Astrophysics Data System (ADS)

Gao, Lingxiang; Zhao, Xiaopeng

The aqueous ER elastomers, containing crude organic starch particles which dispersed in gelatin/glycerin/water matrix, were prepared with or without the applied DC electric field. The responses of the composite systems to the electric field were tested by the compression modulus and resistance of the elastomers. The result shows that they are enhanced and controlled evidently under an applied DC electric field. The strongest responses appear at 25% weight fraction of starch. In addition, the increment modulus of the elastomer increases with the strength of the applied field within 0.5~1.5 kV/mm, while after the field is stronger than 1.5 kV/mm it doesn't increase with field, appearing "saturation".

Proceedings of the International Conference on Electrorheological Fluids (4th) Held in Feldkirch (Austria) on 20-23 July 1993

DTIC Science & Technology

1994-01-01

which predicts that cylinder diameter or spacing has any influence on the dielctric spectra once the concer~tration of cylinders is fixed, and thus...differences in column girth and spacing . Furthermore, in applying the Sillars’ model to the present situation no precise meaning is attached to his end...cm). The test cell comprises two duralumin electrodes 9 cm in diameter spaced by 1.4 cm. Thu planar section of the upper half sphere, solid with a

Novel electrorheological properties of a metal-organic framework Cu3(BTC)2.

PubMed

Liu, Ying Dan; Kim, Jun; Ahn, Wha-Seung; Choi, Hyoung Jin

2012-06-07

A metal-organic framework, Cu(3)(BTC)(2), was synthesized and applied as an electro-responsive electrorheological material dispersed in insulating oil. Powder of crystalline Cu(3)(BTC)(2) exhibited excellent chain-like structures and controllable rheological properties in an applied electric field.

Ultraviolet light-responsive photorheological fluids: as a new class of smart fluids

NASA Astrophysics Data System (ADS)

Cho, Min-Young; Kim, Ji-Sik; Choi, Hyoung Jin; Choi, Seung-Bok; Kim, Gi-Woo

2017-05-01

We present a comprehensive introduction to the photorheological (PR) fluids whose rheological behavior can be changed by ultraviolet (UV) light with a wavelength of 365 nm. When the PR fluid was exposed to UV light, the viscosity of the fluid decreased, while the viscosity recovered to its initial value when UV light was turned off, indicating that the viscosity of these types of fluids can be reversible and tunable by UV light. Contrary to conventional smart fluids, such as electrorheological and magnetorheological fluids, PR fluid does not suffer from a phase splitting problem because it exists in a single-phase solution. Additionally, the PR fluid does not require any contact component, such as electrodes, and electric wires that are essential components for conventional smart fluids. In this work, the PR fluids were synthesized by doping lecithin/sodium deoxycholate reverse micelles with a photo-chromic spiropyran compound. It is demonstrated that the viscosity changes of PR fluids can be induced by UV light, and their rheological properties are examined in detail. In addition, an example of tailoring rheological properties using photoluminescence was introduced for improved response time. One of the potential applications, such as microfluidic flow control using the PR fluids, is also briefly presented.

On necessary conditions for the comparison principle and the sub- and supersolution method for the stationary Kirchhoff equation

NASA Astrophysics Data System (ADS)

Iturriaga, Leonelo; Massa, Eugenio

2018-01-01

In this paper, we propose a counterexample to the validity of the comparison principle and of the sub- and supersolution method for nonlocal problems like the stationary Kirchhoff equation. This counterexample shows that in general smooth bounded domains in any dimension, these properties cannot hold true if the nonlinear nonlocal term M (∥u∥ 2 ) is somewhere increasing with respect to the H01-norm of the solution. Comparing with the existing results, this fills a gap between known conditions on M that guarantee or prevent these properties and leads to a condition that is necessary and sufficient for the validity of the comparison principle. It is worth noting that equations similar to the one considered here have gained interest recently for appearing in models of thermo-convective flows of non-Newtonian fluids or of electrorheological fluids, among others.

ADMiER-ing thin but complex fluids

NASA Astrophysics Data System (ADS)

McDonnell, Amarin G.; Bhattacharjee, Pradipto K.; Pan, Sharadwata; Hill, David; Danquah, Michael K.; Friend, James R.; Yeo, Leslie Y.; Prabhakar, Ranganathan

2011-12-01

The Acoustics Driven Microfluidic Extensional Rheometer (ADMiER) utilises micro litre volumes of liquid, with viscosities as low as that of water, to create valid and observable extensional flows, liquid bridges that pinch off due to capillary forces in this case. ADMiER allows the study fluids that have been beyond conventional methods and also study more subtle fluid properties. We can observe polymeric fluids with solvent viscosities far below those previously testable, accentuating elastic effects. Also, it has enabled the testing of aqueous solutions of living motile particles, which significantly change fluid properties, opening up the potential for diagnostic applications.

Design and integration of an all-in-one biomicrofluidic chip

PubMed Central

Liu, Liyu; Cao, Wenbin; Wu, Jingbo; Wen, Weijia; Chang, Donald Choy; Sheng, Ping

2008-01-01

We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane (PDMS) and silver∕carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing∕analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography. PMID:19693370

Effect of Er,Cr:YSGG laser on human dentin fluid flow.

PubMed

Al-Omari, Wael M; Palamara, Joseph E

2013-11-01

The aim of the current investigation was to assess the rate and magnitude of dentin fluid flow of dentinal surfaces irradiated with Er,Cr:YSGG laser. Twenty extracted third molars were sectioned, mounted, and irradiated with Er,Cr:YSGG laser at 3.5 and 4.5 W power settings. Specimens were connected to an automated fluid flow measurement apparatus (Flodec). The rate, magnitude, and direction of dentin fluid flow were recorded at baseline and after irradiation. Nonparametric Wilcoxon signed ranks repeated measure t test revealed a statistically significant reduction in fluid flow for all the power settings. The 4.5-W power output reduced the flow significantly more than the 3.5 W. The samples showed a baseline outward flow followed by inward flow due to irradiation then followed by decreased outward flow. It was concluded that Er,Cr:YSGG laser irradiation at 3.5 and 4.5 W significantly reduced dentinal fluid flow rate. The reduction was directly proportional to power output.

Performance Analysis of AN Engine Mount Featuring ER Fluids and Piezoactuators

NASA Astrophysics Data System (ADS)

Choi, S. H.; Choi, Y. T.; Choi, S. B.; Cheong, C. C.

Conventional rubber mounts and various types of passive or semi-active hydraulic engine mounts for a passenger vehicle have their own functional aims on the limited frequency band in the broad engine operating frequency range. In order to achieve high system performance over all frequency ranges of the engine operation, a new type of engine mount featuring electro-rheological(ER) fluids and piezoactuators is proposed in this study. A mathematical model of the proposed engine mount is derived using the bond graph method which is inherently adequate to model the interconnected hydromechanical system. In the low frequency domain, the ER fluid is activated upon imposing an electric field for vibration isolation while the piezoactuator is activated in the high frequency domain. A neuro-control algorithm is utilized to determine control electric field for the ER fluid, and H∞ control technique is adopted for the piezoactuator Comparative works between the proposed and single-actuating(ER fluid only or piezoactuator only) engine mounts are undertaken by evaluating force transmissibility over a wide operating frequency range.

Virtual reality robotic telesurgery simulations using MEMICA haptic system

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph; Mavroidis, Constantinos; Bouzit, Mourad; Dolgin, Benjamin; Harm, Deborah L.; Kopchok, George E.; White, Rodney

2001-01-01

The authors conceived a haptic mechanism called MEMICA (Remote Mechanical Mirroring using Controlled stiffness and Actuators) that can enable the design of high dexterity, rapid response, and large workspace haptic system. The development of a novel MEMICA gloves and virtual reality models are being explored to allow simulation of telesurgery and other applications. The MEMICA gloves are being designed to provide intuitive mirroring of the conditions at a virtual site where a robot simulates the presence of a human operator. The key components of MEMICA are miniature electrically controlled stiffness (ECS) elements and electrically controlled force and stiffness (ECFS) actuators that are based on the use of Electro-Rheological Fluids (ERF. In this paper the design of the MEMICA system and initial experimental results are presented.

Method and apparatus for suppressing regenerative instability and related chatter in machine tools

DOEpatents

Segalman, Daniel J.; Redmond, James M.

2001-01-01

Methods of and apparatuses for mitigating chatter vibrations in machine tools or components thereof. Chatter therein is suppressed by periodically or continuously varying the stiffness of the cutting tool (or some component of the cutting tool), and hence the resonant frequency of the cutting tool (or some component thereof). The varying of resonant frequency of the cutting tool can be accomplished by modulating the stiffness of the cutting tool, the cutting tool holder, or any other component of the support for the cutting tool. By periodically altering the impedance of the cutting tool assembly, chatter is mitigated. In one embodiment, a cyclic electric (or magnetic) field is applied to the spindle quill which contains an electro-rheological (or magneto-rheological) fluid. The variable yield stress in the fluid affects the coupling of the spindle to the machine tool structure, changing the natural frequency of oscillation. Altering the modal characteristics in this fashion disrupts the modulation of current tool vibrations with previous tool vibrations recorded on the workpiece surface.

Method and apparatus for suppressing regenerative instability and related chatter in machine tools

DOEpatents

Segalman, Daniel J.; Redmond, James M.

1999-01-01

Methods of and apparatuses for mitigating chatter vibrations in machine tools or components thereof. Chatter therein is suppressed by periodically or continuously varying the stiffness of the cutting tool (or some component of the cutting tool), and hence the resonant frequency of the cutting tool (or some component thereof). The varying of resonant frequency of the cutting tool can be accomplished by modulating the stiffness of the cutting tool, the cutting tool holder, or any other component of the support for the cutting tool. By periodically altering the impedance of the cutting tool assembly, chatter is mitigated. In one embodiment, a cyclic electric (or magnetic) field is applied to the spindle quill which contains an electro-rheological (or magneto-rheological) fluid. The variable yield stress in the fluid affects the coupling of the spindle to the machine tool structure, changing the natural frequency of oscillation. Altering the modal characteristics in this fashion disrupts the modulation of current tool vibrations with previous tool vibrations recorded on the workpiece surface.

Guided self-assembly of nanostructured titanium oxide

NASA Astrophysics Data System (ADS)

Wang, Baoxiang; Rozynek, Zbigniew; Fossum, Jon Otto; Knudsen, Kenneth D.; Yu, Yingda

2012-02-01

A series of nanostructured titanium oxide particles were synthesized by a simple wet chemical method and characterized by means of small-angle x-ray scattering (SAXS)/wide-angle x-ray scattering (WAXS), atomic force microscope (AFM), scanning electron microscope (SEM), transmission electron microscope (TEM), thermal analysis, and rheometry. Tetrabutyl titanate (TBT) and ethylene glycol (EG) can be combined to form either TiOx nanowires or smooth nanorods, and the molar ratio of TBT:EG determines which of these is obtained. Therefore, TiOx nanorods with a highly rough surface can be obtained by hydrolysis of TBT with the addition of cetyl-trimethyl-ammonium bromide (CTAB) as surfactant in an EG solution. Furthermore, TiOx nanorods with two sharp ends can be obtained by hydrolysis of TBT with the addition of salt (LiCl) in an EG solution. The AFM results show that the TiOx nanorods with rough surfaces are formed by the self-assembly of TiOx nanospheres. The electrorheological (ER) effect was investigated using a suspension of titanium oxide nanowires or nanorods dispersed in silicone oil. Oil suspensions of titanium oxide nanowires or nanorods exhibit a dramatic reorganization when submitted to a strong DC electric field and the particles aggregate to form chain-like structures along the direction of applied electric field. Two-dimensional SAXS images from chains of anisotropically shaped particles exhibit a marked asymmetry in the SAXS patterns, reflecting the preferential self-assembly of the particles in the field. The suspension of rough TiOx nanorods shows stronger ER properties than that of the other nanostructured TiOx particles. We find that the particle surface roughness plays an important role in modification of the dielectric properties and in the enhancement of the ER effect.

Guided self-assembly of nanostructured titanium oxide.

PubMed

Wang, Baoxiang; Rozynek, Zbigniew; Fossum, Jon Otto; Knudsen, Kenneth D; Yu, Yingda

2012-02-24

A series of nanostructured titanium oxide particles were synthesized by a simple wet chemical method and characterized by means of small-angle x-ray scattering (SAXS)/wide-angle x-ray scattering (WAXS), atomic force microscope (AFM), scanning electron microscope (SEM), transmission electron microscope (TEM), thermal analysis, and rheometry. Tetrabutyl titanate (TBT) and ethylene glycol (EG) can be combined to form either TiO(x) nanowires or smooth nanorods, and the molar ratio of TBT:EG determines which of these is obtained. Therefore, TiO(x) nanorods with a highly rough surface can be obtained by hydrolysis of TBT with the addition of cetyl-trimethyl-ammonium bromide (CTAB) as surfactant in an EG solution. Furthermore, TiO(x) nanorods with two sharp ends can be obtained by hydrolysis of TBT with the addition of salt (LiCl) in an EG solution. The AFM results show that the TiO(x) nanorods with rough surfaces are formed by the self-assembly of TiO(x) nanospheres. The electrorheological (ER) effect was investigated using a suspension of titanium oxide nanowires or nanorods dispersed in silicone oil. Oil suspensions of titanium oxide nanowires or nanorods exhibit a dramatic reorganization when submitted to a strong DC electric field and the particles aggregate to form chain-like structures along the direction of applied electric field. Two-dimensional SAXS images from chains of anisotropically shaped particles exhibit a marked asymmetry in the SAXS patterns, reflecting the preferential self-assembly of the particles in the field. The suspension of rough TiO(x) nanorods shows stronger ER properties than that of the other nanostructured TiO(x) particles. We find that the particle surface roughness plays an important role in modification of the dielectric properties and in the enhancement of the ER effect.

The Direction of Fluid Dynamics for Liquid Propulsion at NASA Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Griffin, Lisa W.

2012-01-01

The Fluid Dynamics Branch's (ER42) at MSFC mission is to support NASA and other customers with discipline expertise to enable successful accomplishment of program/project goals. The branch is responsible for all aspects of the discipline of fluid dynamics, analysis and testing, applied to propulsion or propulsion-induced loads and environments, which includes the propellant delivery system, combustion devices, coupled systems, and launch and separation events. ER42 supports projects from design through development, and into anomaly and failure investigations. ER42 is committed to continually improving the state-of-its-practice to provide accurate, effective, and timely fluid dynamics assessments and in extending the state-of-the-art of the discipline.

Controllable Sonar Lenses and Prisms Based on ERFs

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph; Sherrit, Stewart; Chang, Zensheu; Bao, Xiaoqi; Paustian, Iris; Lopes, Joseph; Folds, Donald

2004-01-01

Sonar-beam-steering devices of the proposed type would contain no moving parts and would be considerably smaller and less power-hungry, relative to conventional multiple-beam sonar arrays. The proposed devices are under consideration for installation on future small autonomous underwater vehicles because the sizes and power demands of conventional multiple-beam arrays are excessive, and motors used in single-beam mechanically scanned systems are also not reliable. The proposed devices would include a variety of electrically controllable acoustic prisms, lenses, and prism/lens combinations both simple and compound. These devices would contain electrorheological fluids (ERFs) between electrodes. An ERF typically consists of dielectric particles floating in a dielectric fluid. When an electric field is applied to the fluid, the particles become grouped into fibrils aligned in rows, with a consequent increase in the viscosity of the fluid and a corresponding increase in the speed of sound in the fluid. The change in the speed of sound increases with an increase in the applied electric field. By thus varying the speed of sound, one varies the acoustic index of refraction, analogously to varying the index of refraction of an optical lens or prism. In the proposed acoustic devices, this effect would be exploited to control the angles of refraction of acoustic beams, thereby steering the beams and, in the case of lenses, controlling focal lengths.

Active and passive interaction mechanism of smart materials for health monitoring of engineering structures: a review

NASA Astrophysics Data System (ADS)

Annamdas, Venu Gopal Madhav; Annamdas, Kiran Kumar

2009-03-01

Smart materials when interact with engineering structures, should have the capability to sense, measure, process, and detect any change in the selected variables (stress, damage) at critical locations. These smart materials can be classified into active and passive depending on the type of the structure, variables to be monitored, and interaction mechanism due to surface bonding or embedment. Some of the prominent smart materials are piezoelectric materials, micro fiber composite, polymers, shape memory alloys, electrostrictive and magnetostrictive materials, electrorheological and magnetorheological fluids and fiber optics. In addition, host structures do have the properties to support or repel the usage of smart materials inside or on it. This paper presents some of the most widely used smart materials and their interaction mechanism for structural health monitoring of engineering structures.

Computational and Experimental Investigations of the Molecular Scale Structure and Dynamics of Gologically Important Fluids and Mineral-Fluid Interfaces

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

Bowers, Geoffrey

United States Department of Energy grant DE-FG02-10ER16128, “Computational and Spectroscopic Investigations of the Molecular Scale Structure and Dynamics of Geologically Important Fluids and Mineral-Fluid Interfaces” (Geoffrey M. Bowers, P.I.) focused on developing a molecular-scale understanding of processes that occur in fluids and at solid-fluid interfaces using the combination of spectroscopic, microscopic, and diffraction studies with molecular dynamics computer modeling. The work is intimately tied to the twin proposal at Michigan State University (DOE DE-FG02-08ER15929; same title: R. James Kirkpatrick, P.I. and A. Ozgur Yazaydin, co-P.I.).

Active structuring of colloidal armour on liquid drops

NASA Astrophysics Data System (ADS)

Dommersnes, Paul; Rozynek, Zbigniew; Mikkelsen, Alexander; Castberg, Rene; Kjerstad, Knut; Hersvik, Kjetil; Otto Fossum, Jon

2013-06-01

Adsorption and assembly of colloidal particles at the surface of liquid droplets are at the base of particle-stabilized emulsions and templating. Here we report that electrohydrodynamic and electro-rheological effects in leaky-dielectric liquid drops can be used to structure and dynamically control colloidal particle assemblies at drop surfaces, including electric-field-assisted convective assembly of jammed colloidal ‘ribbons’, electro-rheological colloidal chains confined to a two-dimensional surface and spinning colloidal domains on that surface. In addition, we demonstrate the size control of ‘pupil’-like openings in colloidal shells. We anticipate that electric field manipulation of colloids in leaky dielectrics can lead to new routes of colloidosome assembly and design for ‘smart armoured’ droplets.

Active structuring of colloidal armour on liquid drops.

PubMed

Dommersnes, Paul; Rozynek, Zbigniew; Mikkelsen, Alexander; Castberg, Rene; Kjerstad, Knut; Hersvik, Kjetil; Otto Fossum, Jon

2013-01-01

Adsorption and assembly of colloidal particles at the surface of liquid droplets are at the base of particle-stabilized emulsions and templating. Here we report that electrohydrodynamic and electro-rheological effects in leaky-dielectric liquid drops can be used to structure and dynamically control colloidal particle assemblies at drop surfaces, including electric-field-assisted convective assembly of jammed colloidal 'ribbons', electro-rheological colloidal chains confined to a two-dimensional surface and spinning colloidal domains on that surface. In addition, we demonstrate the size control of 'pupil'-like openings in colloidal shells. We anticipate that electric field manipulation of colloids in leaky dielectrics can lead to new routes of colloidosome assembly and design for 'smart armoured' droplets.

Technologies That Enable Accurate and Precise Nano- to Milliliter-Scale Liquid Dispensing of Aqueous Reagents Using Acoustic Droplet Ejection.

PubMed

Sackmann, Eric K; Majlof, Lars; Hahn-Windgassen, Annett; Eaton, Brent; Bandzava, Temo; Daulton, Jay; Vandenbroucke, Arne; Mock, Matthew; Stearns, Richard G; Hinkson, Stephen; Datwani, Sammy S

2016-02-01

Acoustic liquid handling uses high-frequency acoustic signals that are focused on the surface of a fluid to eject droplets with high accuracy and precision for various life science applications. Here we present a multiwell source plate, the Echo Qualified Reservoir (ER), which can acoustically transfer over 2.5 mL of fluid per well in 25-nL increments using an Echo 525 liquid handler. We demonstrate two Labcyte technologies-Dynamic Fluid Analysis (DFA) methods and a high-voltage (HV) grid-that are required to maintain accurate and precise fluid transfers from the ER at this volume scale. DFA methods were employed to dynamically assess the energy requirements of the fluid and adjust the acoustic ejection parameters to maintain a constant velocity droplet. Furthermore, we demonstrate that the HV grid enhances droplet velocity and coalescence at the destination plate. These technologies enabled 5-µL per destination well transfers to a 384-well plate, with accuracy and precision values better than 4%. Last, we used the ER and Echo 525 liquid handler to perform a quantitative polymerase chain reaction (qPCR) assay to demonstrate an application that benefits from the flexibility and larger volume capabilities of the ER. © 2015 Society for Laboratory Automation and Screening.

Active structuring of colloidal armour on liquid drops

PubMed Central

Dommersnes, Paul; Rozynek, Zbigniew; Mikkelsen, Alexander; Castberg, Rene; Kjerstad, Knut; Hersvik, Kjetil; Otto Fossum, Jon

2013-01-01

Adsorption and assembly of colloidal particles at the surface of liquid droplets are at the base of particle-stabilized emulsions and templating. Here we report that electrohydrodynamic and electro-rheological effects in leaky-dielectric liquid drops can be used to structure and dynamically control colloidal particle assemblies at drop surfaces, including electric-field-assisted convective assembly of jammed colloidal ‘ribbons’, electro-rheological colloidal chains confined to a two-dimensional surface and spinning colloidal domains on that surface. In addition, we demonstrate the size control of ‘pupil’-like openings in colloidal shells. We anticipate that electric field manipulation of colloids in leaky dielectrics can lead to new routes of colloidosome assembly and design for ‘smart armoured’ droplets. PMID:23811716

A constitutive theory of reacting electrolyte mixtures

NASA Astrophysics Data System (ADS)

Costa Reis, Martina; Wang, Yongqi; Bono Maurizio Sacchi Bassi, Adalberto

2013-11-01

A constitutive theory of reacting electrolyte mixtures is formulated. The intermolecular interactions among the constituents of the mixture are accounted for through additional freedom degrees to each constituent of the mixture. Balance equations for polar reacting continuum mixtures are accordingly formulated and a proper set of constitutive equations is derived with basis in the Müller-Liu formulation of the second law of thermodynamics. Moreover, the non-equilibrium and equilibrium responses of the reacting mixture are investigated in detail by emphasizing the inner and reactive structures of the medium. From the balance laws and constitutive relations, the effects of molecular structure of constituents upon the fluid flow are studied. It is also demonstrated that the local thermodynamic equilibrium state can be reached without imposing that the set of independent constitutive variables is time independent, neither spatially homogeneous nor null. The resulting constitutive relations presented throughout this work are of relevance to many practical applications, such as swelling of clays, developing of bio and polymeric membranes, and use of electrorheological fluids in industrial processes. The first author acknowledges financial support from National Counsel of Technological and Scientific Development (CNPq) and German Academic Exchange Service (DAAD).

Influence of hang time and location on bacterial contamination of intravenous bags in a veterinary emergency and critical care setting.

PubMed

Guillaumin, Julien; Olp, Nichole M; Magnusson, Karissa D; Butler, Amy L; Daniels, Joshua B

2017-09-01

To assess the rate of bacterial contamination of fluid and ports in intravenous bags in a veterinary emergency room (ER) and intensive care unit (ICU). Experimental model. Ninety intravenous fluid bags of lactated balanced-electrolytes solution (1 L) hung in a university hospital. Bags were hung in 2 different locations in the ER (sink and bins) and one location in the ICU (sink) for 11 days. Bags were punctured 3 times daily with a sterile needle to simulate clinical use. Injection ports were swabbed and 50 mL of fluid were collected in duplicates on days 0, 2, 4, 7, and 10. Aerobic bacterial cultures were performed on the fluid and injection port. Contamination was defined as bacterial growth of a similar phenotype across 2 consecutive times. Increase in the fluid contamination rate from day 0 was tested using an exact binomial test. Port contamination rate between locations was tested using Fisher's exact test. Combined bacterial growth on injection ports reached a mean (95% confidence interval) of 8.1 (0.005-16.2) cfu/port on day 10. The combined port contamination was 3.3%, 11.1%, 17.8%, and 31.1% on days 0, 2, 4, and 7, respectively. Port contamination was similar between ER and ICU. However, port contamination was higher in the sink versus the bins area (38.3% vs 16.7%, P = 0.032). No fluid bag was contaminated at days 0 and 2. The contamination rate of fluid bag was 1.1% and 4.4% on days 4 and 7, respectively. All bags with contaminated fluid were in the ER (6.7%, 95% exact binomial confidence interval 1.9-16.2%). Injection port contamination reached 31.1% on day 7. Contamination was more likely when the bags were hung next to a sink. In our model of bag puncture, fluid contamination occurred between days 2 and 4. © Veterinary Emergency and Critical Care Society 2017.

Temperature Effects of Dielectric Properties of ER Fluids

NASA Astrophysics Data System (ADS)

Qiu, Z. Y.; Hu, L.; Liu, M. W.; Bao, H. X.; Jiang, Y. G.; Zhou, L. W.; Tang, Y.; Gao, Z.; Sun, M.; Korobko, E. V.

Under the consideration of the role that energy transfer and dissipation play in ER effect, an improved theory frame for ER effects, polarization-dissipation-structure-rheology, is suggested. The theory frame is substantiated by the basic physical laws and certain critical experimental facts. The dielectric response of a diatomite ER fluid to temperature is measured in the temperature range of 140 K to 400 K. By comparison of the DC conductivity with the AC effective conductivity of the sample, we found that the AC dielectric loss consists of two parts. One part comes from the DC conductivity, the other from the response of the bound charges in scope of particle to AC field. It is suggested that the response of bound charges is very important to ER effects. Besides, the effect of temperature on shear stress is measured, and interpreted based on the dielectric measurements. The source of two loss peaks in the curve of the dielectric loss versus temperature is not clear.

Development of 3 DOF manipulator using ER fluid clutches for reduction of collision force

NASA Astrophysics Data System (ADS)

Boku, Kazuhiko; Nakamura, Taro

2009-02-01

.With robots and users more commonly sharing space such as in the fields of medicine and home automation, the possibility of a physical collision has increased, even though many robots use actuators with high-ratio gear trains to minimize the effects of impact. We developed a 3-DOF manipulator having a smart flexible joint using an ER fluid and a sensor-equipped pneumatic cushion. Results of position control and collision experiments using the manipulator demonstrated its effectiveness.

Final Technical Report

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

Kirkpatrick, R. James

This document serves as the final report for United States Department of Energy Basic Energy Sciences Grant DE-FG02-08ER15929, “Computational and Spectroscopic Investigations of the Molecular Scale Structure and Dynamics of Geologically Important Fluids and Mineral-Fluid Interfaces” (R. James Kirkpatrick, P.I., A. O. Yazaydin, co-P.I.). The research under this grant was intimately tied to that supported by the parallel the grant of the same title at Alfred (DOE DE-FG02-10ER16128; Geoffrey M. Bowers, P.I.).

An Unconventional Inchworm Actuator Based on PZT/ERFs Control Technology

PubMed Central

Liu, Guojun; Zhang, Yanyan; Liu, Jianfang; Li, Jianqiao; Tang, Chunxiu; Wang, Tengfei; Yang, Xuhao

2016-01-01

An unconventional inchworm actuator for precision positioning based on piezoelectric (PZT) actuation and electrorheological fluids (ERFs) control technology is presented. The actuator consists of actuation unit (PZT stack pump), fluid control unit (ERFs valve), and execution unit (hydraulic actuator). In view of smaller deformation of PZT stack, a new structure is designed for actuation unit, which integrates the advantages of two modes (namely, diaphragm type and piston type) of the volume changing of pump chamber. In order to improve the static shear yield strength of ERFs, a composite ERFs valve is designed, which adopts the series-parallel plate compound structure. The prototype of the inchworm actuator has been designed and manufactured in the lab. Systematic test results indicate that the displacement resolution of the unconventional inchworm actuator reaches 0.038 μm, and the maximum driving force and velocity are 42 N, 14.8 mm/s, respectively. The optimal working frequency for the maximum driving velocity is 120 Hz. The complete research and development processes further confirm the feasibility of developing a new type of inchworm actuator with high performance based on PZT actuation and ERFs control technology, which provides a reference for the future development of a new type of actuator. PMID:27022234

An Unconventional Inchworm Actuator Based on PZT/ERFs Control Technology.

PubMed

Liu, Guojun; Zhang, Yanyan; Liu, Jianfang; Li, Jianqiao; Tang, Chunxiu; Wang, Tengfei; Yang, Xuhao

2016-01-01

An unconventional inchworm actuator for precision positioning based on piezoelectric (PZT) actuation and electrorheological fluids (ERFs) control technology is presented. The actuator consists of actuation unit (PZT stack pump), fluid control unit (ERFs valve), and execution unit (hydraulic actuator). In view of smaller deformation of PZT stack, a new structure is designed for actuation unit, which integrates the advantages of two modes (namely, diaphragm type and piston type) of the volume changing of pump chamber. In order to improve the static shear yield strength of ERFs, a composite ERFs valve is designed, which adopts the series-parallel plate compound structure. The prototype of the inchworm actuator has been designed and manufactured in the lab. Systematic test results indicate that the displacement resolution of the unconventional inchworm actuator reaches 0.038 μm, and the maximum driving force and velocity are 42 N, 14.8 mm/s, respectively. The optimal working frequency for the maximum driving velocity is 120 Hz. The complete research and development processes further confirm the feasibility of developing a new type of inchworm actuator with high performance based on PZT actuation and ERFs control technology, which provides a reference for the future development of a new type of actuator.

Fluid cognitive ability is a resource for successful emotion regulation in older and younger adults

PubMed Central

Opitz, Philipp C.; Lee, Ihno A.; Gross, James J.; Urry, Heather L.

2014-01-01

The Selection, Optimization, and Compensation with Emotion Regulation (SOC-ER) framework suggests that (1) emotion regulation (ER) strategies require resources and that (2) higher levels of relevant resources may increase ER success. In the current experiment, we tested the specific hypothesis that individual differences in one internal class of resources, namely cognitive ability, would contribute to greater success using cognitive reappraisal (CR), a form of ER in which one reinterprets the meaning of emotion-eliciting situations. To test this hypothesis, 60 participants (30 younger and 30 older adults) completed standardized neuropsychological tests that assess fluid and crystallized cognitive ability, as well as a CR task in which participants reinterpreted the meaning of sad pictures in order to alter (increase or decrease) their emotions. In a control condition, they viewed the pictures without trying to change how they felt. Throughout the task, we indexed subjective emotional experience (self-reported ratings of emotional intensity), expressive behavior (corrugator muscle activity), and autonomic physiology (heart rate and electrodermal activity) as measures of emotional responding. Multilevel models were constructed to explain within-subjects variation in emotional responding as a function of ER contrasts comparing increase or decrease conditions with the view control condition and between-subjects variation as a function of cognitive ability and/or age group (older, younger). As predicted, higher fluid cognitive ability—indexed by perceptual reasoning, processing speed, and working memory—was associated with greater success using reappraisal to alter emotional responding. Reappraisal success did not vary as a function of crystallized cognitive ability or age group. Collectively, our results provide support for a key tenet of the SOC-ER framework that higher levels of relevant resources may confer greater success at emotion regulation. PMID:24987387

Fluid cognitive ability is a resource for successful emotion regulation in older and younger adults.

PubMed

Opitz, Philipp C; Lee, Ihno A; Gross, James J; Urry, Heather L

2014-01-01

The Selection, Optimization, and Compensation with Emotion Regulation (SOC-ER) framework suggests that (1) emotion regulation (ER) strategies require resources and that (2) higher levels of relevant resources may increase ER success. In the current experiment, we tested the specific hypothesis that individual differences in one internal class of resources, namely cognitive ability, would contribute to greater success using cognitive reappraisal (CR), a form of ER in which one reinterprets the meaning of emotion-eliciting situations. To test this hypothesis, 60 participants (30 younger and 30 older adults) completed standardized neuropsychological tests that assess fluid and crystallized cognitive ability, as well as a CR task in which participants reinterpreted the meaning of sad pictures in order to alter (increase or decrease) their emotions. In a control condition, they viewed the pictures without trying to change how they felt. Throughout the task, we indexed subjective emotional experience (self-reported ratings of emotional intensity), expressive behavior (corrugator muscle activity), and autonomic physiology (heart rate and electrodermal activity) as measures of emotional responding. Multilevel models were constructed to explain within-subjects variation in emotional responding as a function of ER contrasts comparing increase or decrease conditions with the view control condition and between-subjects variation as a function of cognitive ability and/or age group (older, younger). As predicted, higher fluid cognitive ability-indexed by perceptual reasoning, processing speed, and working memory-was associated with greater success using reappraisal to alter emotional responding. Reappraisal success did not vary as a function of crystallized cognitive ability or age group. Collectively, our results provide support for a key tenet of the SOC-ER framework that higher levels of relevant resources may confer greater success at emotion regulation.

A new neuro-fuzzy training algorithm for identifying dynamic characteristics of smart dampers

NASA Astrophysics Data System (ADS)

Dzung Nguyen, Sy; Choi, Seung-Bok

2012-08-01

This paper proposes a new algorithm, named establishing neuro-fuzzy system (ENFS), to identify dynamic characteristics of smart dampers such as magnetorheological (MR) and electrorheological (ER) dampers. In the ENFS, data clustering is performed based on the proposed algorithm named partitioning data space (PDS). Firstly, the PDS builds data clusters in joint input-output data space with appropriate constraints. The role of these constraints is to create reasonable data distribution in clusters. The ENFS then uses these clusters to perform the following tasks. Firstly, the fuzzy sets expressing characteristics of data clusters are established. The structure of the fuzzy sets is adjusted to be suitable for features of the data set. Secondly, an appropriate structure of neuro-fuzzy (NF) expressed by an optimal number of labeled data clusters and the fuzzy-set groups is determined. After the ENFS is introduced, its effectiveness is evaluated by a prediction-error-comparative work between the proposed method and some other methods in identifying numerical data sets such as ‘daily data of stock A’, or in identifying a function. The ENFS is then applied to identify damping force characteristics of the smart dampers. In order to evaluate the effectiveness of the ENFS in identifying the damping forces of the smart dampers, the prediction errors are presented by comparing with experimental results.

On-Command Force and Torque Impeding Devices (OC-FTID) Using ERF

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph; Badescu, Mircea; Sherrit, Stewart

2014-01-01

Various machines have been developed to address the need for countermeasures of bone and muscle deterioration when humans operate over extended time in space. Even though these machines are in use, each of them has many limitations that need to be addressed in an effort to prepare for human missions to distant bodies in the solar system. An exercise exoskeleton was conceived that performs on-demand resistivity by inducing force and torque impedance via ElectroRheological Fluid (ERF). The resistive elements consist of pistons that are moving inside ERF-filled cylinders or a donut-shaped cavity, and the fluid flows through the piston when the piston is moved. Tests of the operation of ERF against load showed the feasibility of this approach. ERF properties of high yield stress, low current density, and fast response (less than one millisecond) offer essential characteristics for the construction of the exoskeleton. ERFs can apply very high electrically controlled resistive forces or torque while their size (weight and geometric parameters) can be very small. Their long life and ability to function in a wide temperature range (from -40 to 200 C) allows for their use in extreme environments. ERFs are also nonabrasive, non-toxic, and nonpolluting (meet health and safety regulations). The technology is applicable as a compact exercise machine for astronauts' countermeasure of microgravity, an exercise machine for sport, or as a device for rehabilitation of patients with limb issues.

Visualization of irrigant flow and cavitation induced by Er:YAG laser within a root canal model.

PubMed

Matsumoto, Himeka; Yoshimine, Yoshito; Akamine, Akifumi

2011-06-01

Laser-activated irrigation (LAI) has recently been introduced as an innovative method for root canal irrigation. However, there is limited information about the cleaning mechanism of an Er:YAG laser. In this study, we visualized the action of laser-induced bubbles and fluid flow in vitro to better understand the physical mechanisms underlying LAI. An Er:YAG laser was equipped with a novel cone-shaped tip with a lateral emission rate of approximately 80%. Laser light was emitted at a pulse energy of 30, 50, or 70 mJ (output energy: 11, 18, or 26 mJ) and a repetition rate of 1 or 20 pulses per second, without air or water spray. Fluid flow dynamics in a root canal model were observed by using glass-bead tracers under a high-speed camera. Moreover, laser-induced bubble patterns were visualized in both free water and the root canal model. Tracers revealed high-speed motion of the fluid. A full cycle of expansion and implosion of vapor and secondary cavitation bubbles were clearly observed. In free water, the vapor bubble expanded for 220 microseconds, and its shape resembled that of an apple. In the root canal model, the vapor bubble expanded in a vertical direction along the canal wall, and bubble expansion continued for ≥700 microseconds. Furthermore, cavitation bubbles were created much more frequently in the canal model than in free water. These results suggest that the cleaning mechanism of an Er:YAG laser within the root canal might depend on rapid fluid motion caused by expansion and implosion of laser-induced bubbles. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Nanotechnology research for aerospace applications

NASA Astrophysics Data System (ADS)

Agee, Forrest J.; Lozano, Karen; Gutierrez, Jose M.; Chipara, Mircea; Thapa, Ram; Chow, Alice

2009-04-01

Nanotechnology is impacting the future of the military and aerospace. The increasing demands for high performance and property-specific applications are forcing the scientific world to take novel approaches in developing programs and accelerating output. CONTACT or Consortium for Nanomaterials for Aerospace Commerce and Technology is a cooperative nanotechnology research program in Texas building on an infrastructure that promotes collaboration between universities and transitioning to industry. The participants of the program include the US Air Force Research Laboratory (AFRL), five campuses of the University of Texas (Brownsville, Pan American, Arlington, Austin, and Dallas), the University of Houston, and Rice University. Through the various partnerships between the intellectual centers and the interactions with AFRL and CONTACT's industrial associates, the program represents a model that addresses the needs of the changing and competitive technological world. Into the second year, CONTACT has expanded to twelve projects that cover four areas of research: Adaptive Coatings and Surface Engineering, Nano Energetics, Electromagnetic Sensors, and Power Generation and Storage. This paper provides an overview of the CONTACT program and its projects including the research and development of new electrorheological fluids with nanoladen suspensions and composites and the potential applications.

Effects of ICI 182780 on estrogen receptor expression, fluid absorption and sperm motility in the epididymis of the bonnet monkey

PubMed Central

Shayu, Deshpande; Kesava, Chenna CS; Soundarajan, Rama; Rao, A Jagannadha

2005-01-01

Background The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. However, functional studies on the role of estrogen in primate epididymis have been few. The main objective of this study was therefore to extend these observations and systematically analyze the presence and function of estrogen receptors in modulating the function of the primate epididymis, using the bonnet monkey (Macaca radiata) as a model system. Methods A steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was administered to adult male bonnet monkeys via mini-osmotic pumps for a duration of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further, the effect of ICI in modulating fluid reabsorption in efferent ductules was monitored, and critical sperm-maturation parameters were also analyzed. Results Our studies in the bonnet monkey revealed that both ER-alpha and ER-beta were expressed in all the three regions of the epididymis. We observed an increase in ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA levels of the water-channel protein, Aquaporin-1, was significantly lower in the caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na-K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules with ICI resulted in two-fold increase in tubular diameter, indicating affected fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were immotile. Conclusion Taken together, our results point to an integral role for estrogen in modulating the functions of the bonnet monkey epididymis. This study also demonstrates possible differences in the epididymal physiology of rodents and non-human primates, and thus underscores the significance of reports such as these, that examine the physiology of non-human primates (as opposed to rodents), in an attempt to understand similar events in the human. PMID:15743524

Effects of ICI 182780 on estrogen receptor expression, fluid absorption and sperm motility in the epididymis of the bonnet monkey.

PubMed

Shayu, Deshpande; ChennaKesava, C S; Soundarajan, Rama; Rao, A Jagannadha

2005-03-02

The importance of estrogen in regulation of fluid absorption and sperm maturation in the rodent epididymis has been established from studies on estrogen receptor-alpha knockout mice. However, functional studies on the role of estrogen in primate epididymis have been few. The main objective of this study was therefore to extend these observations and systematically analyze the presence and function of estrogen receptors in modulating the function of the primate epididymis, using the bonnet monkey (Macaca radiata) as a model system. A steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was administered to adult male bonnet monkeys via mini-osmotic pumps for a duration of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further, the effect of ICI in modulating fluid reabsorption in efferent ductules was monitored, and critical sperm-maturation parameters were also analyzed. Our studies in the bonnet monkey revealed that both ER-alpha and ER-beta were expressed in all the three regions of the epididymis. We observed an increase in ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA levels of the water-channel protein, Aquaporin-1, was significantly lower in the caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na-K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules with ICI resulted in two-fold increase in tubular diameter, indicating affected fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were immotile. Taken together, our results point to an integral role for estrogen in modulating the functions of the bonnet monkey epididymis. This study also demonstrates possible differences in the epididymal physiology of rodents and non-human primates, and thus underscores the significance of reports such as these, that examine the physiology of non-human primates (as opposed to rodents), in an attempt to understand similar events in the human.

Application of electron closures in extended MHD

NASA Astrophysics Data System (ADS)

Held, Eric; Adair, Brett; Taylor, Trevor

2017-10-01

Rigorous closure of the extended MHD equations in plasma fluid codes includes the effects of electron heat conduction along perturbed magnetic fields and contributions of the electron collisional friction and stress to the extended Ohms law. In this work we discuss application of a continuum numerical solution to the Chapman-Enskog-like electron drift kinetic equation using the NIMROD code. The implementation is a tightly-coupled fluid/kinetic system that carefully addresses time-centering in the advance of the fluid variables with their kinetically-computed closures. Comparisons of spatial accuracy, computational efficiency and required velocity space resolution are presented for applications involving growing magnetic islands in cylindrical and toroidal geometry. The reduction in parallel heat conduction due to particle trapping in toroidal geometry is emphasized. Work supported by DOE under Grant Nos. DE-FC02-08ER54973 and DE-FG02-04ER54746.

Dynamic Electrorheological Effects of Rotating Particles:

NASA Astrophysics Data System (ADS)

Yu, K. W.; Gu, G. Q.; Huang, J. P.; Xiao, J. J.

Particle rotation leads to a steady-state which is different from the equilibrium state in the absence of rotational motion. The change of the polarization of the particle due to the rotational motion is called the dynamic electrorheological effect (DER). There are three cases to be considered: rotating particles in a dc field, particle rotation due to a rotating field and spontaneous rotation of particle in dc field (Quincke rotation). In the DER of rotating particles, the particle rotational motion generally reduces the interparticle force between the particles. The effect becomes pronounced when the frequency is on the order of the relaxation rate of the surface charges. In the electrorotation of particles, the mutual interaction between approaching particles will change the electrorotation spectrum significantly. The electrorotation spectrum depends strongly on the medium conductivity as well as the conductivity contrast between the particle and the medium. In the collective behaviors of Quincke rotors, the mutual interactions between the individual rotors lead to the assembly of chain-like structures which make an angle with the applied field. This has an implication of a new class of material.

Electrorheology leads to healthier and tastier chocolate.

PubMed

Tao, Rongjia; Tang, Hong; Tawhid-Al-Islam, Kazi; Du, Enpeng; Kim, Jeongyoo

2016-07-05

Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. Although this issue was called into attention decades ago, no actual solution was found. To bypass this critical outstanding problem, two manufacturers introduced some low-calorie fats to substitute for cocoa butter. Somehow, their products are not allowed in most countries. Here we show that this issue is deeply related to the basic science of soft matter, especially to the viscosity of liquid suspension and maximally random jammed (MRJ) density. When the concentration of cocoa solid is high, close to the MRJ density, removing a small amount of fat will jam the chocolate flow. Applying unconventional electrorheology to liquid chocolate with applied field in the flow direction, we aggregate the cocoa particles into prolate spheroids in micrometers. This microstructure change breaks the rotational symmetry, reduces liquid chocolate's viscosity along the flow direction, and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are expecting a new class of healthier and tastier chocolate soon.

Electrorheology leads to healthier and tastier chocolate

PubMed Central

Tao, Rongjia; Tang, Hong; Tawhid-Al-Islam, Kazi; Du, Enpeng; Kim, Jeongyoo

2016-01-01

Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. Although this issue was called into attention decades ago, no actual solution was found. To bypass this critical outstanding problem, two manufacturers introduced some low-calorie fats to substitute for cocoa butter. Somehow, their products are not allowed in most countries. Here we show that this issue is deeply related to the basic science of soft matter, especially to the viscosity of liquid suspension and maximally random jammed (MRJ) density. When the concentration of cocoa solid is high, close to the MRJ density, removing a small amount of fat will jam the chocolate flow. Applying unconventional electrorheology to liquid chocolate with applied field in the flow direction, we aggregate the cocoa particles into prolate spheroids in micrometers. This microstructure change breaks the rotational symmetry, reduces liquid chocolate’s viscosity along the flow direction, and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are expecting a new class of healthier and tastier chocolate soon. PMID:27325758

Organelle Redox of CF and CFTR-Corrected Airway Epithelia

PubMed Central

Schwarzer, Christian; Illek, Beate; Suh, Jung H.; Remington, S. James; Fischer, Horst; Machen, Terry E.

2014-01-01

In cystic fibrosis reduced CFTR function may alter redox properties of airway epithelial cells. Redox-sensitive GFP (roGFP1) and imaging microscopy were used to measure redox potentials of cytosol, ER, mitochondria and cell surface of cystic fibrosis nasal epithelial cells and CFTR-corrected cells. We also measured glutathione and cysteine thiol redox states in cell lysates and apical fluids to provide coverage over a range of redox potentials and environments that might be affected by CFTR. As measured with roGFP1, redox potentials at the cell surface (~ -207 ±8 mV) and in the ER (~ -217 ±1 mV) and rates of regulation of the apical fluid and ER lumen following DTT treatment were similar for CF and CFTR-corrected cells. CF and CFTR-corrected cells had similar redox potentials in mitochondria (-344 ±9 mV) and cytosol (-322 ±7 mV). Oxidation of carboxy-dichlorodihydrofluoresceindiacetate and of apical Amplex Red occurred at equal rates in CF and CFTR-corrected cells. Glutathione and cysteine redox couples in cell lysates and apical fluid were equal in CF and CFTR-corrected cells. These quantitative estimates of organelle redox potentials combined with apical and cell measurements using small molecule couples confirmed there were no differences in redox properties of CF and CFTR-corrected cells. PMID:17603939

Help is in your pocket: the potential accuracy of smartphone- and laptop-based remotely guided resuscitative telesonography.

PubMed

McBeth, Paul; Crawford, Innes; Tiruta, Corina; Xiao, Zhengwen; Zhu, George Qiaohao; Shuster, Michael; Sewell, Les; Panebianco, Nova; Lautner, David; Nicolaou, Savvas; Ball, Chad G; Blaivas, Michael; Dente, Christopher J; Wyrzykowski, Amy D; Kirkpatrick, Andrew W

2013-12-01

Ultrasound (US) examination has many uses in resuscitation, but to use it to its full effectiveness typically requires a trained and proficient user. We sought to use information technology advances to remotely guide US-naive examiners (UNEs) using a portable battery-powered tele-US system mentored using either a smartphone or laptop computer. A cohort of UNEs (5 tactical emergency medicine technicians, 10 ski-patrollers, and 4 nurses) was guided to perform partial or complete Extended Focused Assessment with Sonography of Trauma (EFAST) examinations on both a healthy volunteer and on a US phantom, while being mentored by a remote examiner who viewed the US images over either an iPhone(®) (Apple, Cupertino, CA) or a laptop computer with an inlaid depiction of the US probe and the "patient," derived from a videocamera mounted on the UNE's head. Examinations were recorded as still images and over-read from a Web site by seven expert reviewers (ERs) (three surgeons, two emergentologists, and two radiologists). Examination goals were to identify lung sliding (LS) documented by color power Doppler (CPD) in the human and to identify intraperitoneal (IP) fluid in the phantom. All UNEs were successfully mentored to easily and clearly identify both LS (19 determinations) and IP fluid (14 determinations), as assessed in real time by the remote mentor. ERs confirmed IP fluid in 95 of 98 determinations (97%), with 100% of ERs perceiving clinical utility for the abdominal Focused Assessment with Sonography of Trauma. Based on single still CPD images, 70% of ERs agreed on the presence or absence of LS. In 16 out of 19 cases, over 70% of the ERs felt the EFAST exam was clinically useful. UNEs can confidently be guided to obtain critical findings using simple information technology resources, based on the receiving/transmitting device found in most trauma surgeons' pocket or briefcase. Global US mentoring requires only Internet connectivity and initiative.

Improving the seismic torsional behavior of plan-asymmetric, single-storey, concrete moment resisting buildings with fluid viscous dampers

NASA Astrophysics Data System (ADS)

Rofooei, Fayaz Rahimzadeh; Mohammadzadeh, Sahar

2016-03-01

The optimal distribution of fluid viscous dampers (FVD) in controlling the seismic response of eccentric, single-storey, moment resisting concrete structures is investigated using the previously defined center of damping constant (CDC). For this purpose, a number of structural models with different one-way stiffness and strength eccentricities are considered. Extensive nonlinear time history analyses are carried out for various arrangements of FVDs. It is shown that the arrangement of FVDs for controlling the torsional behavior due to asymmetry in the concrete structures is very dependent on the intensity of the peak ground acceleration (PGA) and the extent of the structural stiffness and strength eccentricities. The results indicate that, in the linear range of structural behavior the stiffness eccentricity es which is the main parameter in determining the location of optimal CDC, is found to be less or smaller than the optimal damping constant eccentricity e*d, i.e., |e*d| > |es|. But, in the nonlinear range of structural behavior where the strength eccentricity er is the dominant factor in determining the location of optimal CDC, |e*d| > |er|. It is also concluded that for the majority of the plan-asymmetric, concrete structures considered in this study with er ≠ 0, the optimal CDC approaches the center of mass as er decreases.

Laser induced explosive vapor and cavitation resulting in effective irrigation of the root canal. Part 1: a visualization study.

PubMed

Blanken, Jan; De Moor, Roeland Jozef Gentil; Meire, Maarten; Verdaasdonk, Rudolf

2009-09-01

Limited information exists regarding the induction of explosive vapor and cavitation bubbles in an endodontic rinsing solution. It is also not clear whether a fiber has to be moved in the irrigation solution or can be kept stationary. No information is available on safe power settings for the use of cavitation in the root canal. This study investigates the fluid movements and the mechanism of action caused by an Er,Cr:YSGG laser in a transparent root model. Glass models with an artificial root canal (15 mm long, with a 0.06 taper and apical diameter of 400 microm) were used for visualization and registration with a high-speed imaging technique (resolution in the microsecond range) of the creation of explosive vapor bubbles with an Er,Cr:YSGG laser at pulse energies of 75, 125, and 250 mJ at 20 Hz using a 200 microm fiber (Z2 Endolase). Fluid movement was investigated by means of dyes and visualization of the explosive vapor bubbles, and as a function of pulse energy and distance of the fiber tip to the apex. The recordings in the glass model show the creation of expanding and imploding vapor bubbles with secondary cavitation effects. Dye is flushed out of the canal and replaced by surrounding fluid. It seems not necessary to move the fiber close to the apex. Imaging suggests that the working mechanism of an Er,Cr:YSGG laser in root canal treatment in an irrigation solution can be attributed to cavitation effects inducing high-speed fluid motion into and out the canal.

CK-MB Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... Missouri. Pp. 312-315. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER and ...

Blood Urea Nitrogen Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... mmol/L 1 from Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns ...

Electric-field induced phase transitions of dielectric colloids: Impact of multiparticle effects

NASA Astrophysics Data System (ADS)

Wood, Jeffery A.; Docoslis, Aristides

2012-05-01

The thermodynamic framework for predicting the electric-field induced fluid like-solid like phase transition of dielectric colloids developed by Khusid and Acrivos [Phys. Rev. E. 54, 5428 (1996)] is extended to examine the impact of multiscattering/multiparticle effects on the resulting phase diagrams. This was accomplished using effective permittivity models suitable both over the entire composition region for hard spheres (0≤c

Neutron Scattering Studies of Classical and Quantum Fluids in Porous Media

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

Glyde, Henry R.

This is an annual and the final report on DE-FG02-03ER46038 (ER46680) following a no cost extension of DE-FG02-03ER46038 from February 16, 2016 to November 15, 2016. The report period is February 16, 2016 to November 15, 2016. The contract DE-FG02-03ER46038 (ER46680) was closed on November 15, 2016. The contract institution is the University of Delaware, address: Room 210, Hullihen %%@ Hall, University of Delaware, Newark, DE 19716. The Principal Investigator is Henry R. Glyde, Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (email: glyde@udel.edu). The Administrative Point of Contact is Dale S. Weiss Tel: 302 831 3634more » dsweiss@udel.edu. The DOE Program is the Office of Basic Energy %%@ Sciences, U.S. Department of Energy, Germantown Building, 1000 Independence Ave., SW Washington, DC 20585. The program manager is Dr. P. Thiyagarajan, Neutron Scattering SC-22.2/ Germantown Bldg., Tel: 301-903-9706, email: P. Thiyagarajan@Science.DOE.GOV.« less

Palpation imaging using a haptic system for virtual reality applications in medicine.

PubMed

Khaled, W; Reichling, S; Bruhns, O T; Boese, H; Baumann, M; Monkman, G; Egersdoerfer, S; Klein, D; Tunayar, A; Freimuth, H; Lorenz, A; Pessavento, A; Ermert, H

2004-01-01

In the field of medical diagnosis, there is a strong need to determine mechanical properties of biological tissue, which are of histological and pathological relevance. Malignant tumors are significantly stiffer than surrounding healthy tissue. One of the established diagnosis procedures is the palpation of body organs and tissue. Palpation is used to measure swelling, detect bone fracture, find and measure pulse, or to locate changes in the pathological state of tissue and organs. Current medical practice routinely uses sophisticated diagnostic tests through magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) imaging. However, they cannot provide direct measure of tissue elasticity. Last year we presented the concept of the first haptic sensor actuator system to visualize and reconstruct mechanical properties of tissue using ultrasonic elastography and a haptic display with electrorheological fluids. We developed a real time strain imaging system for tumor diagnosis. It allows biopsies simultaneously to conventional ultrasound B-Mode and strain imaging investigations. We deduce the relative mechanical properties by using finite element simulations and numerical solution models solving the inverse problem. Various modifications on the haptic sensor actuator system have been investigated. This haptic system has the potential of inducing real time substantial forces, using a compact lightweight mechanism which can be applied to numerous areas including intraoperative navigation, telemedicine, teaching and telecommunication.

Polymorphic organization of the endoplasmic reticulum of the Malpighian tubule. Evidence for a transcellular route.

PubMed

Berthelet, F; Beaudry-Lonergan, M; Linares, H; Whittembury, G; Bergeron, M

1987-01-01

Isosmotic fluid absorption carried out by many mammalian epithelia appears to be similar to the isosmotic secretion of insect epithelia such as the Malpighian tubules, which are responsible for urine formation and osmoregulation. We have studied by electron microscopy (80 kV) the three-dimensional characteristics of organelles in the Malpighian tubules of Rhodnius prolixus using thick sections (0.3-0.5 microns) and uranyl and lead impregnation. The ER presents a different organization in the upper (distal) and lower (proximal) segments of the Malpighian tubule. In distal secretory segment, the ER forms a network made of chains of vesicles having irregular shapes (ca. 0.06 micron in diameter) connected to each other by canaliculi while in the lower absorptive segment, the ER is made of parallel saccules arranged in stacks or whorls in the central region of the cytoplasm. In both segments, the ER network extends throughout the cytoplasm from the basolateral infoldings to the apex between the many mitochondria present in these two areas. A unique feature of these cells, revealed by thick sections, is the presence in each microvillus of either a mitochondrion or an ER canaliculus in continuity with the ER network. The ER does not seem to have any specific association with mitochondria or other organelles. As in the mammalian nephron, this ER organization is most likely related to specific segmental functions and adds support to its potential role as a transcellular epithelial route.

Characterization of Antimicrobial Agent Loaded Eudragit RS Solvent Exchange-Induced In Situ Forming Gels for Periodontitis Treatment.

PubMed

Phaechamud, Thawatchai; Jantadee, Takron; Mahadlek, Jongjan; Charoensuksai, Purin; Pichayakorn, Wiwat

2017-02-01

Eudragit RS (ERS), a quaternary polyacrylate positively charged polymer, exhibits a very low permeability and swells in aqueous media independently of pH without dissolving. Owing to its high solubility in N-methyl pyrrolidone (NMP), it was interesting to apply as polymer matrix for solvent-exchanged in situ forming gel. The aim of this research was to prepare in situ forming gels from ERS to deliver the antimicrobial agents (doxycycline hyclate, metronidazole, and benzoyl peroxide) for periodontitis treatment. They were evaluated for viscosity and rheology, gel formation, syringeability, drug release, and antimicrobial activities. The solvent exchange between NMP and an external aqueous simulated gingival crevicular fluid stimulated the dissolved ERS transforming into the opaque rigid gel. Antimicrobial agent loaded ERS systems exhibited Newtonian flow with acceptable syringeability. The higher-loaded ERS promoted the more prolongation of drug release because of the retardation of water diffusion into the precipitated matrix. Antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis depended on type of drugs and test microorganisms. Doxycycline hyclate loaded ERS systems showed these activities greater than the others; however, all of them could inhibit all test microorganisms. Thus, the solvent exchange-induced in situ forming gels comprising ERS-antimicrobial drugs exhibited potential use as localized delivery systems for periodontitis treatment.

Exclusive nuclear location of estrogen receptors in Squalus testis.

PubMed Central

Callard, G V; Mak, P

1985-01-01

An estrogen (E)-binding molecule having both occupied and unoccupied sites is restricted to nuclear subfractions in the testis of the spiny dogfish (Squalus acanthias). We investigated the hypothesis that a species characterized by high body-fluid osmolarity (1010 mosM) has an estrogen receptor (ER) that binds to chromatin with high affinity and consequently resists redistribution during tissue processing. Although the steroid binding and sedimentation properties of the Squalus nuclear ER conformed to those of classical ER, its elution maximum from DNA-cellulose was unusually high (0.55 M NaCl). A tendency to adhere tightly to cell nuclei was reflected in the high salt concentration (0.43 M KCl) required to extract 50% of the receptors from the nuclear compartment during homogenization and in the stability of the nuclear ER population in the presence of high concentrations of a nonionic solute (urea) or increased buffer volume. Mixing and redistribution experiments showed that nuclear ER could be quantitatively and qualitatively measured in cytosolic extracts, ruling out the possibility that soluble receptors were being masked. Although Squalus oviduct ER was similar to that of testis, ER in the testis and liver of a related elasmobranch (Potamotrygon) that maintains osmotic equilibrium at 300 mosM more closely resembled mammalian ER in its elution maximum from DNA-cellulose (0.22 M NaCl) and cytosolic/nuclear ratios in low-salt buffers. We conclude that Squalus testis has a single ER pool located exclusively in the nuclear compartment. These observations support a revised concept of steroid action and further indicate that the chromatin affinity of the hormone-ER complex is an important factor in determining subfractional distribution during tissue processing. PMID:3856265

Evaluation of dentin tubule occlusion after laser irradiation and desensitizing agent application.

PubMed

Kim, Min-Ho; Kim, Ryan Jin-Young; Lee, Woo-Cheol; Lee, In-Bog

2015-10-01

To evaluate the effects of lasers (Nd:YAG and Er:YAG) and of topical desensitizing agents on dentin tubule occlusion by measuring real-time dentin fluid flow (DFF). 32 molars were prepared with V-shape cavity at the cervical area, acid-etched, water rinsed, blotted dry, and treated with (1) Nd:YAG laser; (2) Er:YAG laser; (3) SuperSeal, a desensitizing agent; (4) ClinproXT, a resin-modified glass-ionomer (RMGI) varnish (n = 8 each). A real-time fluid flow measuring instrument (nano-Flow) was used to measure the DFF throughout the procedures. The DFF rates before and after the treatment were compared. Moreover, the surface topography of dentin tubules after each desensitizing method was examined using SEM. DFF varied among the groups. The DFF rate was significantly reduced after laser irradiation/application of the desensitizing agents (P < 0.05). ClinproXT showed the greatest reduction of DFF rate (71.9%), followed by the SuperSeal (34.8%) and laser groups (P< 0.05). However, there was no significant difference between the Nd:YAG (24.1%) and Er:YAG (20.6%) groups (P > 0.05). In SEM images, narrowed dentin tubules were observed in both lased groups and SuperSeal group. In the ClinproXT group, the occluded dentin tubules by the RMGI covering were observed.

Detection of Orexin A Neuropeptide in Biological Fluids Using a Zinc Oxide Field Effect Transistor

DTIC Science & Technology

2012-06-01

can rapidly cross the blood-brain barrier10. In contrast, orexin B has low lipophilicity and is rapidly metabolized in blood which makes it difficult...Tris (Sigma) pH 9.1. The eluate was added to 20 mL E. coli ER2738 culture and incubated at 37 ºC with vigorous shaking for 4.5 h. The culture was...plates using a sterile inoculation loops, and were amplified individually for 4.5-5 hours at 37 ºC in 1.5 mL of E. coli ER2738 culture grown in LB broth

The Direction of Fluid Dynamics for Liquid Propulsion at NASA Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Griffin, Lisa W.

2012-01-01

Marshall Space Flight Center (MSFC) is the National Aeronautics and Space Administration (NASA)-designated center for the development of space launch systems. MSFC is particularly known for propulsion system development. Many engineering skills and technical disciplines are needed to accomplish this mission. This presentation will focus on the work of the Fluid Dynamics Branch (ER42). ER42 resides in the Propulsion Systems Department at MSFC. The branch is responsible for all aspects of the discipline of fluid dynamics applied to propulsion or propulsion-induced loads and environments. This work begins with design trades and parametric studies, and continues through development, risk assessment, anomaly investigation and resolution, and failure investigations. Applications include the propellant delivery system including the main propulsion system (MPS) and turbomachinery; combustion devices for liquid engines and solid rocket motors; coupled systems; and launch environments. An advantage of the branch is that it is neither analysis nor test centric, but discipline centric. Fluid dynamics assessments are made by analysis, from lumped parameter modeling through unsteady computational fluid dynamics (CFD); testing, which can be cold flow or hot fire; or a combination of analysis and testing. Integration of all discipline methods into one branch enables efficient and accurate support to the projects. To accomplish this work, the branch currently employs approximately fifty engineers divided into four teams -- Propellant Delivery CFD, Combustion Driven Flows CFD, Unsteady and Experimental Flows, and Acoustics and Stability. This discussion will highlight some of the work performed in the branch and the direction in which the branch is headed.

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

Rotman, D.

After nearly a decade of work and $150 million in development costs. Exxon Research and Engineering (ER&E; Florham Park, NJ) says its natural gas conversion process based on Fischer-Tropsch technology is ready for full-scale commercialization. ER&E is looking to entice one of Exxon`s other business units into building a plant based on the process. The Exxon technology makes refinery or petrochemical feedstocks from natural gas in an integrated three-step process, including fluid-bed reactor to make synthesis gas and a hydrocarbon synthesis step using a proprietary Fischer-Tropsch catalyst. Exxon has successfully demonstrated the process at a pilot plant in Baton Rouge,more » LA but says no commercialization decision has been made. ER&E estimates that to commercialize the technology economically will require a large gas conversion plant-with a price tag of about $2 billion.« less

Hydrodynamic resistance parameters for ErPr rare-earth regenerator material under steady and periodic flow conditions

NASA Astrophysics Data System (ADS)

Pathak, M. G.; Helvensteijn, B. P.; Patel, V. C.; Ghiaasiaan, S. M.; Mulcahey, T. I.; Kashani, A.; Feller, J. R.

2014-01-01

The regenerator, typically a microporous structure that is subject to periodic flow of a cryogenic fluid, is a critical component of pulse tube or Stirling cryocoolers, which are widely used for high-demand aerospace and defense applications. In this investigation, experiments were conducted in which steady and oscillatory flows of helium were imposed on ErPr rare-Earth regenerator filler material and mass flow and pressure drop data were recorded under ambient temperature conditions. A computational fluid dynamics (CFD)-assisted method was applied for the analysis and interpretation of the experimental data. The permeability and inertial coefficients that lead to agreement between the experimental data and computational simulations were iteratively obtained. The Darcy permeability and Forchheimer inertial coefficients were obtained and were found to be functions of the system charge pressure, operating frequency, and compressor piston stroke within the studied range of interest. The results also exhibit that the periodic flow hydrodynamic resistance parameters are in general different than steady flow parameters.

For Debate: Personalized Health Care: As Exemplified by Home Sodium Measurements in a Child with Central Diabetes Insipidus and Impaired Thirst Perception.

PubMed

van der Linde, A A A; van Herwaarden, A E; Oosting, J D; Claahsen-van der Grinten, H L; de Grouw, E P L M

2018-04-01

We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance. In order to provide better self-reliance, home point of care testing (POCT) sodium measurement was introduced. Realizing POCT sodium measurement resulted in a significant decrease of ER visits and clinical admissions due to dysregulation of fluid balance. This case is an example of personalized health care and has led to better self-reliance and quality of life. Copyright© of YS Medical Media ltd.

NIMROD modeling of poloidal flow damping in tokamaks using kinetic closures

NASA Astrophysics Data System (ADS)

Jepson, J. R.; Hegna, C. C.; Held, E. D.

2017-10-01

Calculations of poloidal flow damping in a tokamak are undertaken using two different implementations of the ion drift kinetic equation (DKE) in the extended MHD code NIMROD. The first approach is hybrid fluid/kinetic and uses a Chapman Enskog-like (CEL) Ansatz. Closure of the evolving lower-order fluid moment equations for n, V , and T is provided by solutions to the ion CEL-DKE written in the macroscopic flow reference frame. The second implementation solves the DKE using a delta-f approach. Here, the delta-f distribution describes all of the information beyond a static, lowest-order Maxwellian. We compare the efficiency and accuracy of these two approaches for a simple initial value problem that monitors the relaxation of the poloidal flow profile in high- and low-aspect-ratio tokamak geometry. The computation results are compared against analytic predictions of time dependent closures for the parallel viscous force. Supported by DoE Grants DE-FG02-86ER53218 and DE-FG02-04ER54746.

QuEChERS sample preparation for the determination of pesticides and other organic residues in environmental matrices: a critical review.

PubMed

Bruzzoniti, Maria Concetta; Checchini, Leonardo; De Carlo, Rosa Maria; Orlandini, Serena; Rivoira, Luca; Del Bubba, Massimo

2014-07-01

Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) is an extraction and clean-up technique originally developed for recovering pesticide residues from fruits and vegetables. Since its introduction, and until December 2013, about 700 papers have been published using the QuEChERS technique, according to a literature overview carried out using SciFinder, Elsevier SciVerse, and Google search engines. Most of these papers were dedicated to pesticide multiresidue analysis in food matrices, and this topic has been thoroughly reviewed over recent years. The QuEChERS approach is now rapidly developing beyond its original field of application to analytes other than pesticides, and matrices other than food, such as biological fluids and non-edible plants, including Chinese medicinal plants. Recently, the QuEChERS concept has spread to environmental applications by analyzing not only pesticides but also other compounds of environmental concern in soil, sediments, and water. To the best of our knowledge, QuEChERS environmental applications have not been reviewed so far; therefore, in this contribution, after a general discussion on the evolution and changes of the original QuEChERS method, a critical survey of the literature regarding environmental applications of conventional and modified QuEChERS methodology is provided. The overall recoveries obtained with QuEChERS and other extraction approaches (e.g., accelerated solvent extraction, ultrasonic solvent extraction, liquid/solid extraction, and soxhlet extraction) were compared, providing evidence for QuEChERS higher recoveries for various classes of compounds, such as biopesticides, chloroalkanes, phenols, and perfluoroalkyl substances. The role of physicochemical properties of soil (i.e., clay and organic carbon content, as well as cation exchange capacity) and target analytes (i.e., log KOW, water solubility, and vapor pressure) were also evaluated in order to interpret recovery and matrix effect data.

Correlation of chemical evaporation rate with vapor pressure.

PubMed

Mackay, Donald; van Wesenbeeck, Ian

2014-09-02

A new one-parameter correlation is developed for the evaporation rate (ER) of chemicals as a function of molar mass (M) and vapor pressure (P) that is simpler than existing correlations. It applies only to liquid surfaces that are unaffected by the underlying solid substrate as occurs in the standard ASTM evaporation rate test and to quiescent liquid pools. The relationship has a sounder theoretical basis than previous correlations because ER is correctly correlated with PM rather than P alone. The inclusion of M increases the slope of previous log ER versus log P regressions to a value close to 1.0 and yields a simpler one-parameter correlation, namely, ER (μg m(-1) h(-1)) = 1464P (Pa) × M (g mol(-1)). Applications are discussed for the screening level assessment and ranking of chemicals for evaporation rate, such as pesticides, fumigants, and hydrocarbon carrier fluids used in pesticide formulations, liquid consumer products used indoors, and accidental spills of liquids. The mechanistic significance of the single parameter as a mass-transfer coefficient or velocity is discussed.

Future automotive materials: Evolution or revolution

NASA Technical Reports Server (NTRS)

Beardmore, P.

1990-01-01

An exciting era is evolving in the application of new materials technologies to automotive applications. The desire on the part of the automobile industry to completely satisfy the customers while concurrently meeting increasing demands and regulations for stringent emission control and fuel efficiency is opening a plethora of opportunities for new materials. In many cases, materials solutions are the only mechanisms for resolving some of the upcoming issues. The materials scientist and engineer will therefore have a primary role to play and will assume a position of significance hithertofore unseen in the automobile industry. The nature of the industry dictates that changes are primarily evolutionary with respect to chronology but nevertheless some of the future material changes will be revolutionary in nature. This presentation will treat three primary systems of the vehicle separately, based on the different materials approaches which will be adopted. These areas are: (1) skin panels, (2) structures, and (3) powertrains. The competition between a variety of new materials in these 3 systems will be discussed in detail with the various tradeoffs being outlined. Amongst the more prominent of the new breed of materials will be new steel technologies, structural plastics (FRP), aluminum alloys (conventional and rapidly solidified), titanium alloys, metal matrix composites and smart materials (electrorheological fluids, etc.). The pace of development and application is accelerating rapidly and the impetus is likely to increase.

Three different methods for the derivation of control laws for multi-degree-of-freedom systems containing electrorheological dampers

NASA Astrophysics Data System (ADS)

Moosheimer, Johannes; Waller, Heinz

1999-06-01

The minimization of unwanted vibrations is an important technical challenge. Purely passive systems often do not achieve the postulated results. Purely active systems are costly because of the required additional power and the necessary maintenance. Currently it seems that semi-active methods of vibration reduction are as competitive as any other methods. Semi-active damping control can be realized with electro- or magnetorheological fluids. These change their characteristic in the presence of an electric or magnetic field or by bypasses combined with magnetic valves. The methods known in linear control theory cannot be used for the controller design because no explicit external forces can be generated whenever they are needed. Forces can only be generated when relative velocities between the endpoints of the damper exist. It is important to investigate control methods which will reduce vibration with controlled damping. In this paper three different methods for establishing control laws are presented. The first is based on the consideration of power flow in the system. It is discussed in detail. The second method uses Bellmans dynamic optimization. The last transforms a multi degree of freedom system by modal analysis into uncoupled single degree of freedom systems. The control methods developed by these three methods all lead to the same vibration reduction strategy. The control laws are verified with simulation results.

Nonlinear Fluid Model Of 3-D Field Effects In Tokamak Plasmas

NASA Astrophysics Data System (ADS)

Callen, J. D.; Hegna, C. C.; Beidler, M. T.

2017-10-01

Extended MHD codes (e.g., NIMROD, M3D-C1) are beginning to explore nonlinear effects of small 3-D magnetic fields on tokamak plasmas. To facilitate development of analogous physically understandable reduced models, a fluid-based dynamic nonlinear model of these added 3-D field effects in the base axisymmetric tokamak magnetic field geometry is being developed. The model incorporates kinetic-based closures within an extended MHD framework. Key 3-D field effects models that have been developed include: 1) a comprehensive modified Rutherford equation for the growth of a magnetic island that includes the classical tearing and NTM perturbed bootstrap current drives, externally applied magnetic field and current drives, and classical and neoclassical polarization current effects, and 2) dynamic nonlinear evolution of the plasma toroidal flow (radial electric field) in response to the 3-D fields. An application of this model to RMP ELM suppression precipitated by an ELM crash will be discussed. Supported by Office of Fusion Energy Sciences, Office of Science, Dept. of Energy Grants DE-FG02-86ER53218 and DE-FG02-92ER54139.

The β-amyloid peptide compromises Reelin signaling in Alzheimer’s disease

PubMed Central

Cuchillo-Ibañez, Inmaculada; Mata-Balaguer, Trinidad; Balmaceda, Valeria; Arranz, Juan José; Nimpf, Johannes; Sáez-Valero, Javier

2016-01-01

Reelin is a signaling protein that plays a crucial role in synaptic function, which expression is influenced by β-amyloid (Aβ). We show that Reelin and Aβ oligomers co-immunoprecipitated in human brain extracts and were present in the same size-exclusion chromatography fractions. Aβ treatment of cells led to increase expression of Reelin, but secreted Reelin results trapped together with Aβ aggregates. In frontal cortex extracts an increase in Reelin mRNA, and in soluble and insoluble (guanidine-extractable) Reelin protein, was associated with late Braak stages of Alzheimer’s disease (AD), while expression of its receptor, ApoER2, did not change. However, Reelin-dependent induction of Dab1 phosphorylation appeared reduced in AD. In cells, Aβ reduced the capacity of Reelin to induce internalization of biotinylated ApoER2 and ApoER2 processing. Soluble proteolytic fragments of ApoER2 generated after Reelin binding can be detected in cerebrospinal fluid (CSF). Quantification of these soluble fragments in CSF could be a tool to evaluate the efficiency of Reelin signaling in the brain. These CSF-ApoER2 fragments correlated with Reelin levels only in control subjects, not in AD, where these fragments diminished. We conclude that while Reelin expression is enhanced in the Alzheimer’s brain, the interaction of Reelin with Aβ hinders its biological activity. PMID:27531658

Er Effect of Low Molecular Liquid Crystal on One-Sided Patterned Electrodes

NASA Astrophysics Data System (ADS)

Kikuchi, Takehito; Inoue, Akio; Furusho, Junji; Kawamuki, Ryohei

Several kinds of ER fluids (ERF) have been developed and have been applied to some mechatronics devices and processing technologies. In many conventional applications of ERFs, these devices consist of bilateral electrodes to apply electric field in ERF. However, the electric field of several kV/mm may be necessary to generate an ER effect sufficiently for practical purposes. The gap between a pair of electrodes should be, therefore, maintained narrowly and exactly for fears of short-circuit. At the same time, this electrode system also requires an interconnection on driving parts. To improve these disadvantages, we proposed "one-sided patterned electrode" (OSPE) systems in previous works. In this report, we confirmed the flow characteristics of low molecular liquid crystal (LMLC) on OSPE. Next, we also confirmed the different characteristics depending on the pattern type. Depending on results of electro-static analysis, we conclude that such a difference may results from the directors of LC molecules derived by electric field.

Optical high-resolution analysis of rotational movement: testing circular spatial filter velocimetry (CSFV) with rotating biological cells

NASA Astrophysics Data System (ADS)

Schaeper, M.; Schmidt, R.; Kostbade, R.; Damaschke, N.; Gimsa, J.

2016-07-01

Circular spatial filtering velocimetry (CSFV) was tested during the microscopic registration of the individual rotations of baker’s yeast cells. Their frequency-dependent rotation (electrorotation; ER) was induced in rotating electric fields, which were generated in a glass chip chamber with four electrodes (600 μm tip-to-tip distance). The electrodes were driven with sinusoidal quadrature signals of 5 or 8 V PP with frequencies up to 3 MHz. The observed cell rotation was of the order of 1-100 s per revolution. At each measuring frequency, the independent rotations of up to 20 cells were simultaneously recorded with a high-speed camera. CSFV was software-implemented using circular spatial filters with harmonic gratings. ER was proportional to the phase shift between the values of the spatial filtering signal of consecutive frames. ER spectra obtained by CSFV from the rotation velocities at different ER-field frequencies agreed well with manual measurements and theoretical spectra. Oscillations in the rotation velocity of a single cell in the elliptically polarized field near an electrode, which were resolved by CSFV, could not be visually discerned. ER step responses after field-on were recorded at 2500 frames per second. Analysis proved the high temporal resolution of CSFV and revealed a largely linear torque-friction relation during the acceleration phase of ER. Future applications of CSFV will allow for the simple and cheap automated high-resolution analysis of rotational movements where mechanical detection has too low a resolution or is not possible, e.g. in polluted environments or for gas and fluid vortices, microscopic objects, etc.

Outcomes of exertional rhabdomyolysis following high-intensity resistance training.

PubMed

Huynh, A; Leong, K; Jones, N; Crump, N; Russell, D; Anderson, M; Steinfort, D; Johnson, D F

2016-05-01

High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. To compare the clinical outcomes of ER with other causes of rhabdomyolysis. Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies. © 2016 Royal Australasian College of Physicians.

Electrorheology for energy production and conservation

NASA Astrophysics Data System (ADS)

Huang, Ke

Recently, based on the physics of viscosity, we developed a new technology, which utilizes electric or magnetic fields to change the rheology of complex fluids to reduce the viscosity, while keeping the temperature unchanged. The method is universal and applicable to all complex fluids with suspended particles of nano-meter, submicrometer, or micrometer size. Completely different from the traditional viscosity reduction method, raising the temperature, this technology is energy-efficient, as it only requires small amount of energy to aggregate the suspended particles. In this thesis, we will first discuss this new technology in detail, both in theory and practice. Then, we will report applications of our technology to energy science research. Presently, 80% of all energy sources are liquid fuels. The viscosity of liquid fuels plays an important role in energy production and energy conservation. With an electric field, we can reduce the viscosity of asphalt-based crude oil. This is important and useful for heavy crude oil and off-shore crude oil production and transportation. Especially, since there is no practical way to raise the temperature of crude oil inside the deepwater pipelines, our technology may play a key role in future off-shore crude oil production. Electrorehology can also be used to reduce the viscosity of refinery fuels, such as diesel fuel and gasoline. When we apply this technology to fuel injection, the fuel droplets in the fuel atomization become smaller, leading to faster combustion in the engine chambers. As the fuel efficiency of internal combustion engines depends on the combustion speed and timing, the fast combustion produces much higher fuel efficiency. Therefore, adding our technology on existing engines improves the engine efficiency significantly. A theoretical model for the engine combustion, which explains how fast combustion improves the engine efficiency, is also presented in the thesis. As energy is the key to our national security, we believe that our technology is important and will have a strong impact on energy production and conversation in the future.

A symbiotic approach to fluid equations and non-linear flux-driven simulations of plasma dynamics

NASA Astrophysics Data System (ADS)

Halpern, Federico

2017-10-01

The fluid framework is ubiquitous in studies of plasma transport and stability. Typical forms of the fluid equations are motivated by analytical work dating several decades ago, before computer simulations were indispensable, and can be, therefore, not optimal for numerical computation. We demonstrate a new first-principles approach to obtaining manifestly consistent, skew-symmetric fluid models, ensuring internal consistency and conservation properties even in discrete form. Mass, kinetic, and internal energy become quadratic (and always positive) invariants of the system. The model lends itself to a robust, straightforward discretization scheme with inherent non-linear stability. A simpler, drift-ordered form of the equations is obtained, and first results of their numerical implementation as a binary framework for bulk-fluid global plasma simulations are demonstrated. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences, Theory Program, under Award No. DE-FG02-95ER54309.

Linear instabilities near the DIII-D edge simulated in fluid models

NASA Astrophysics Data System (ADS)

Bass, Eric; Holland, Christopher

2017-10-01

The linear instability spectrum is reported near the DIII-D edge (within the separatrix) for L-mode and H-mode shots using the new eigenvalue solver FluTES (Fluid Toroidal Eigenvalue Solver). FluTES circumvents difficulties with convergence to clean linear eigenmodes (required for diagnosis of nonlinear simulations in codes such as BOUT++) often encountered with fluid initial-value solvers. FluTES is well-verified in analytic cases and against a BOUT++/ELITE benchmark toroidal case. We report results for both a 3-field, one-fluid model (the well-known ``elm-pb'' model) and a 5-field, two-fluid model. For the peeling-ballooning-dominated H-mode, the two solutions are qualitatively the same. In the driftwave-dominated L-mode edge, only the two-fluid solution gives robust instabilities which occur primarily at n > 50 . FluTES is optimized for this regime (near-flutelike limit, toroidally spectral). Cross-separatrix, coupled fluid and drift instabilities may play a role in explaining the gyrokinetic L-mode edge transport shortfall. Extension of FluTES into the open-field-line region is underway. Prepared by UCSD under Contract Number DE-FG02-06ER54871.

The effect of fluid overload on sleep apnoea severity in haemodialysis patients.

PubMed

Lyons, Owen D; Inami, Toru; Perger, Elisa; Yadollahi, Azadeh; Chan, Christopher T; Bradley, T Douglas

2017-04-01

As in heart failure, obstructive and central sleep apnoea (OSA and CSA, respectively) are common in end-stage renal disease. Fluid overload characterises end-stage renal disease and heart failure, and in heart failure plays a role in the pathogenesis of OSA and CSA. We postulated that in end-stage renal disease patients, those with sleep apnoea would have greater fluid volume overload than those without.End-stage renal disease patients on thrice-weekly haemodialysis underwent overnight polysomnography on a nondialysis day to determine their apnoea-hypopnoea index (AHI). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance.28 patients had an AHI ≥15 (sleep apnoea group; OSA:CSA 21:7) and 12 had an AHI <15 (no sleep apnoea group). Total body extracellular fluid volume was 2.6 L greater in the sleep apnoea group than in the no sleep apnoea group (p=0.006). Neck, thorax, and leg fluid volumes were also greater in the sleep apnoea than the no sleep apnoea group (p<0.05), despite no difference in body mass index (p=0.165).These findings support a role for fluid overload in the pathogenesis of both OSA and CSA in end-stage renal disease. Copyright ©ERS 2017.

Experimental Program to Stimulate Competitive Research (EPSCoR)

NASA Technical Reports Server (NTRS)

Dingerson, Michael R.

1997-01-01

Report includes: (1) CLUSTER: "Studies in Macromolecular Behavior in Microgravity Environment": The Role of Protein Oligomers in Protein Crystallization; Phase Separation Phenomena in Microgravity; Traveling Front Polymerizations; Investigating Mechanisms Affecting Phase Transition Response and Changes in Thermal Transport Properties in ER-Fluids under Normal and Microgravity Conditions. (2) CLUSTER: "Computational/Parallel Processing Studies": Flows in Local Chemical Equilibrium; A Computational Method for Solving Very Large Problems; Modeling of Cavitating Flows.

Virtual Reality Robotic Operation Simulations Using MEMICA Haptic System

NASA Technical Reports Server (NTRS)

Bar-Cohen, Y.; Mavroidis, C.; Bouzit, M.; Dolgin, B.; Harm, D. L.; Kopchok, G. E.; White, R.

2000-01-01

There is an increasing realization that some tasks can be performed significantly better by humans than robots but, due to associated hazards, distance, etc., only a robot can be employed. Telemedicine is one area where remotely controlled robots can have a major impact by providing urgent care at remote sites. In recent years, remotely controlled robotics has been greatly advanced. The robotic astronaut, "Robonaut," at NASA Johnson Space Center is one such example. Unfortunately, due to the unavailability of force and tactile feedback capability the operator must determine the required action using only visual feedback from the remote site, which limits the tasks that Robonaut can perform. There is a great need for dexterous, fast, accurate teleoperated robots with the operator?s ability to "feel" the environment at the robot's field. Recently, we conceived a haptic mechanism called MEMICA (Remote MEchanical MIrroring using Controlled stiffness and Actuators) that can enable the design of high dexterity, rapid response, and large workspace system. Our team is developing novel MEMICA gloves and virtual reality models to allow the simulation of telesurgery and other applications. The MEMICA gloves are designed to have a high dexterity, rapid response, and large workspace and intuitively mirror the conditions at a virtual site where a robot is simulating the presence of the human operator. The key components of MEMICA are miniature electrically controlled stiffness (ECS) elements and Electrically Controlled Force and Stiffness (ECFS) actuators that are based on the sue of Electro-Rheological Fluids (ERF). In this paper the design of the MEMICA system and initial experimental results are presented.

Nonlinear electromagnetic gyrokinetic particle simulations with the electron hybrid model

NASA Astrophysics Data System (ADS)

Nishimura, Y.; Lin, Z.; Chen, L.; Hahm, T.; Wang, W.; Lee, W.

2006-10-01

The electromagnetic model with fluid electrons is successfully implemented into the global gyrokinetic code GTC. In the ideal MHD limit, shear Alfven wave oscillation and continuum damping is demonstrated. Nonlinear electromagnetic simulation is further pursued in the presence of finite ηi. Turbulence transport in the AITG unstable β regime is studied. This work is supported by Department of Energy (DOE) Grant DE-FG02-03ER54724, Cooperative Agreement No. DE-FC02-04ER54796 (UCI), DOE Contract No. DE-AC02-76CH03073 (PPPL), and in part by SciDAC Center for Gyrokinetic Particle Simulation of Turbulent Transport in Burning Plasmas. Z. Lin, et al., Science 281, 1835 (1998). F. Zonca and L. Chen, Plasma Phys. Controlled Fusion 30, 2240 (1998); G. Zhao and L. Chen, Phys. Plasmas 9, 861 (2002).

Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.

PubMed

Sutton-McDowall, Melanie L; Wu, Linda L Y; Purdey, Malcolm; Abell, Andrew D; Goldys, Ewa M; MacMillan, Keith L; Thompson, Jeremy G; Robker, Rebecca L

2016-01-01

Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulus-oocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stress-mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation. © 2016 by the Society for the Study of Reproduction, Inc.

Isoflavone genistein inhibits estrogen-induced chloride and bicarbonate secretory mechanisms in the uterus in rats.

PubMed

Chinigarzadeh, Asma; Karim, Kamarulzaman; Muniandy, Sekaran; Salleh, Naguib

2017-04-01

We hypothesized that genistein could affect the chloride (Cl - ) and bicarbonate (HCO 3 - ) secretory mechanisms in uterus. Ovariectomized female rats were given estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein. Following completion of the treatment, uterine fluid Cl - and HCO 3 - concentrations were determined by in vivo uterine perfusion. Uteri were subjected for molecular biological analysis (Western blot, qPCR, and immunohistochemistry) to detect levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl - /HCO 3 - exchanger (SLC26a6), Na + /HCO 3 - cotransporter (SLC4a4), and estrogen receptor (ER)-α and β. Coadministration of genistein resulted in decrease in Cl - and HCO 3 - concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-α and ER-β in the uteri of estradiol-treated rats. In estradiol plus progesterone-treated rats, a significant increase in the above parameters were observed following high-dose genistein treatment except for the SLC24a4 level. In conclusion, genistein-induced changes in the uterus could affect the reproductive processes that might result in infertility. © 2016 Wiley Periodicals, Inc.

Pore blocking: An innovative formulation strategy for the design of alcohol resistant multi-particulate dosage forms.

PubMed

Schrank, Simone; Jedinger, Nicole; Wu, Shengqian; Piller, Michael; Roblegg, Eva

2016-07-25

In this work calcium stearate (CaSt) multi-particulates loaded with codeine phosphate (COP) were developed in an attempt to provide extended release (ER) combined with alcohol dose dumping (ADD) resistance. The pellets were prepared via wet/extrusion spheronization and ER characteristics were obtained after fluid bed drying at 30°C. Pore blockers (i.e., xanthan, guar gum and TiO2) were integrated to control the uptake of ethanolic media, the CaSt swelling and consequently, the COP release. While all three pore blockers are insoluble in ethanol, xanthan dissolves, guar gum swells and TiO2 does not interact with water. The incorporation of 10 and 15% TiO2 still provided ER characteristics and yielded ADD resistance in up to 40v% ethanol. The in-vitro data were subjected to PK simulations, which revealed similar codeine plasma levels when the medication is used concomitantly with alcoholic beverages. Taken together the in-vitro and in-silico results demonstrate that the incorporation of appropriate pore blockers presents a promising strategy to provide ADD resistance of multi-particulate systems. Copyright © 2016 Elsevier B.V. All rights reserved.

The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

PubMed

Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

2016-01-01

Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects.

A state-of-the-art assessment of active structures

NASA Technical Reports Server (NTRS)

1992-01-01

A state-of-the-art assessment of active structures with emphasis towards the applications in aeronautics and space is presented. It is felt that since this technology area is growing at such a rapid pace in many different disciplines, it is not feasible to cover all of the current research but only the relevant work as relates to aeronautics and space. Research in smart actuation materials, smart sensors, and control of smart/intelligent structures is covered. In smart actuation materials, piezoelectric, magnetostrictive, shape memory, electrorheological, and electrostrictive materials are covered. For sensory materials, fiber optics, dielectric loss, and piezoelectric sensors are examined. Applications of embedded sensors and smart sensors are discussed.

Completion Report for Well ER-20-12: Corrective Action Units 101 and 102: Central and Western Pahute Mesa

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

Wurtz, Jeff

2016-08-01

Well ER-20-12 was drilled for the U.S. Department of Energy, Nevada National Security Administration Nevada Field Office in support of the Underground Test Area Activity. The well was drilled from October 2015 to January 2016 as an addition to the Central and Western Pahute Mesa corrective action units 101 and 102 the Phase II drilling program. Well ER-20-12 was identified based on recommendations of the Pahute Mesa Guidance Team as a result of anomalous tritium detections in groundwater samples collected from Well PM-3 in 2011 and 2013. The primary purpose of the well was to provide information on the hydrogeologymore » in the area downgradient of select underground tests on Western Pahute Mesa and define hydraulic properties in the saturated Tertiary volcanic rocks. The main 46.99-centimeter (cm) (18.5-inch [in.]) borehole was drilled to a depth of 765.14 meters (m) (2,510.3 ft) and the hole opened to 66.04 cm (26 in.); followed by the 50.80-cm (20-in.) surface casing, which was installed and sealed with cement; and a piezometer (p4) was set in the Timber Mountain welded-tuff aquifer (TMWTA) between the casing and the open borehole. The borehole was continued with a 46.99-cm (18.5-in.) drill bit to a depth of 1,326.53 m (4,352.16 ft), and an intermediate 24.44-cm (9.625-in.) casing was installed and sealed to 1,188.72 m (3,900.00 ft) A piezometer (p3) was installed across the Calico Hills zeolitic composite unit (CHZCM) (lava-flow aquifer [LFA]) in the annulus of the open borehole. Two additional piezometers were installed and completed between the intermediate casing and the borehole wall, one (p2) in the CHZCM and one (p1) in the Belted Range aquifer (BRA). The piezometers are set to monitor groundwater properties in the completed intervals. The borehole was continued with a 21.59-cm (8.5-in.) drill bit to a total depth of 1,384.80 m (4,543.33 ft), and the main completion 13.97-cm (5.5-in.) casing was installed in the open borehole across the Pre-Belted Range composite unit (PBRCM). Data collected during hole construction include composite drill cutting samples collected every 3.0 m (10 ft), geophysical logs, hydrophysical logs, percussion core samples, water-quality measurements (including tritium), and water-level measurements. The well penetrated 1,384.4 m (4,543.33 ft) of Tertiary volcanic rocks. The stratigraphy and lithology were generally as expected with one noted exception. A thick lava-flow and related ash-flow tuffs were identified as Calico Hills Formation (Th), and no Crater Flat units were noted. Additionally, many of the Thirsty Canyon and Timber Mountain units were thicker than expected. Fluid levels measured in the borehole during drilling are the following: (1) on November 2, 2015, Navarro measured the fluid level in the borehole at a depth of 492.33 m (1,615.25 ft) below ground surface (bgs); (2) Schlumberger and COLOG recorded fluid levels during geophysical logging on November 4 and 5, 2015, at a depth of 492.86 m (1,617 ft) and 492.25 m (1,615 ft) bgs, respectively; and (3) on December 4, 2015, COLOG and Navarro measured fluid level in the 20-in. casing with an open borehole to 1,326.54 m (4,352.16 ft) bgs at 575.77 m (1,889.00 ft) and 574.03 m (1,883.3 ft) bgs, respectively. These and subsequent water-level measurements indicate a potential head difference of greater than 76.2 m (250 ft) for groundwater in aquifers above and below the Upper Paintbrush confining unit (UPCU). As expected, tritium was occasionally measured above the Safe Drinking Water Act limit (20,000 picocuries per liter [pCi/L]). Lab analysis on four bailed samples and taken from the undeveloped well indicate that the tritium activities average approximately 36,545 pCi/L. All Fluid Management Plan (FMP) requirements for Well ER-20-12 were met. Analysis of monitoring samples and FMP confirmatory samples indicate that fluids generated during drilling at ER-20-12 met the FMP criteria for discharge to the lined sump and designated infiltration area. All sanitary and hydrocarbon waste generated was properly handled and disposed of.« less

Flow in Smectic Liquid Crystal Films: Examining the Flow Field of a Smectic Liquid Crystal Film due to Fluid Ejected From a Small Nozzle

NASA Astrophysics Data System (ADS)

Ferguson, Kyle; Qi, Zhiyuan; Park, Cheol; Maclennan, Jospeh; Glaser, Matthew; Clark, Noel

The rheological properties of 2D fluids are well-understood theoretically, but few experiments testing theoretical predictions have been carried out. We have used MX 12805, a smectic C liquid crystal at room temperature, to create quasi-2D films with which to study high-Reynolds number flow. We map the flow field as the fluid is ejected from a thin nozzle into a large reservoir, probing both laminar and turbulent flow. We also attempt to carry out the experiment in a vacuum to study the true 2D-regime; despite encountering experimental difficulties, some useful information can still be gleaned. This work was supported by NASA Grant NNX-13AQ81G, by the Soft Materials Research Center under NSF MRSEC Grants DMR-0820579 and DMR-1420736, by Department of Energy Grant DE-FG02-08ER54995, and by NSF Grant CBET-0854108.

78 FR 25377 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

...We are adopting a new airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, -900 and -900ER series airplanes. This AD was prompted by a report of leaking fuel from the wing leading edge area at the inboard end of the number 5 leading edge slat. This AD requires modifying the fluid drain path in the wing leading edge area, forward of the wing front spar, and doing all applicable related investigative and corrective actions; and installing new seal disks on the latches in the fuel shutoff valve access door. We are issuing this AD to prevent flammable fluids from accumulating in the wing leading edge, and draining inboard and onto the engine exhaust nozzle, which could result in a fire.

Deployable Acoustic Projector System (DAPS) Energy Source Study

DTIC Science & Technology

1988-12-01

dLfficulties. I This cathode wet !_ fi- film wae introduced into the Spame Mittle ’E fuel cell technology program and the U.S. Navy’s HASPA W’E fuel cell...tbm off ers the potential for low cost os.ruction. In this co•iguratim , a wet -oofsII electrode suport boixied to the ozygen electrode provies...water is fed from the orygen fluid caerto a storae vesel . The major orygen subsystem[ auzillary and =mitorizV compaonats which are required izxabde

Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

PubMed

González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Sánchez-Martínez, Ruth; Vargas, Teodoro; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

2014-06-01

Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mesoscale Variability in SUCCESS Data

NASA Technical Reports Server (NTRS)

Eckermann, Stephen D.

1998-01-01

Analysis of meteorological, chemical, and microphysical data from the airborne SUCCESS mission is reported. Careful analysis of the complex DC-8 flight pattern of May 2, 1996 reveals 19 linear or nearly linear flight segments within six main geographical areas, which we have analyzed. Significant mountain wave activity is revealed in the data from the MMS and MTP instruments on the DC-8, which resembles previous observations of mountain wave structures near Boulder, CO. Strong mountain-wave-induced upwelling downwind of the Rockies is noted. Turbulence is also noted in regions of the mountain wave consistent with overturning near the tropopause. Zonal winds recorded on the ER-2 are shown to consistent with mountain wave breaking at or near critical levels in the stratosphere, consistent with the strong turbulence reported by the pilot during the ER-2 flight. Those observations have been supported with spectral analyses and modeling studies. "Postcasts" of mountain wave activity on May 2, 1996, using the Naval Research Laboratory Mountain Wave Forecast Model (NRL/MWFM) predicts both strong mountain wave activity near the tropopause (as measured by the DC-8) and strong mountain-wave-induced turbulence in the stratosphere (as encountered by the ER-2). Two-dimensional simulations of fluid flow over topography reveal similar isentropic structures to observations.

Calculation of stochastic broadening due to low mn magnetic perturbation in the simple map in action-angle coordinates

NASA Astrophysics Data System (ADS)

Hinton, Courtney; Punjabi, Alkesh; Ali, Halima

2009-11-01

The simple map is the simplest map that has topology of divertor tokamaks [A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Let. A 364, 140--145 (2007)]. Recently, the action-angle coordinates for simple map are analytically calculated, and simple map is constructed in action-angle coordinates [O. Kerwin, A. Punjabi, and H. Ali, Phys. Plasmas 15, 072504 (2008)]. Action-angle coordinates for simple map cannot be inverted to real space coordinates (R,Z). Because there is logarithmic singularity on the ideal separatrix, trajectories cannot cross separatrix [op cit]. Simple map in action-angle coordinates is applied to calculate stochastic broadening due to the low mn magnetic perturbation with mode numbers m=1, and n=±1. The width of stochastic layer near the X-point scales as 0.63 power of the amplitude δ of low mn perturbation, toroidal flux loss scales as 1.16 power of δ, and poloidal flux loss scales as 1.26 power of δ. Scaling of width deviates from Boozer-Rechester scaling by 26% [A. Boozer, and A. Rechester, Phys. Fluids 21, 682 (1978)]. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793.

Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles.

PubMed

Antic, Bratislav; Boskovic, Marko; Nikodinovic-Runic, Jasmina; Ming, Yue; Zhang, Hongguo; Bozin, Emil S; Janković, Drina; Spasojevic, Vojislav; Vranjes-Djuric, Sanja

2017-06-01

Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in the MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er) 3 O 4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6-7nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90K. Reduction in saturation magnetization due to incorporation of 1.7% Er 3+ into the Fe 3 O 4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er) 3 O 4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90 Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er) 3 O 4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. This work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er) 3O 4 coated nanoparticles

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

Antic, Bratislav; Boskovic, Marko; Nikodinovic-Runic, Jasmina

Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in themore » MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er) 3O 4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6–7 nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90 K. Reduction in saturation magnetization due to incorporation of 1.7% Er 3+ into the Fe 3O 4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er) 3O 4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish ( Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er) 3O 4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. Lastly, this work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems.« less

Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er) 3O 4 coated nanoparticles

DOE PAGES

Antic, Bratislav; Boskovic, Marko; Nikodinovic-Runic, Jasmina; ...

2017-02-10

Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in themore » MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er) 3O 4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6–7 nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90 K. Reduction in saturation magnetization due to incorporation of 1.7% Er 3+ into the Fe 3O 4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er) 3O 4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish ( Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er) 3O 4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. Lastly, this work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems.« less

Expression of the estrogen receptors and steroidogenic enzymes involved in estradiol formation in the monkey vagina.

PubMed

Bertin, Jonathan; Ouellet, Johanne; Dury, Alain Yves; Pelletier, Georges; Labrie, Fernand

2014-11-01

Estrogens are well recognized to have beneficial effects on vulvovaginal atrophy because of menopause. The distribution of estrogen receptors and enzymes responsible for estradiol (E2) formation within the vagina may provide insight into how dehydroepiandrosterone, a precursor of both estrogens and androgens, improves vulvovaginal atrophy. The purpose of the study was to determine where the steroidogenic enzymes responsible for E2 formation as well as estrogen receptors are localized in vaginal specimens collected from cynomolgus monkeys (Macaca fascicularis), the closest model to the human. HSD3B1, HSD17B1, HSD17B5, HSD17B12, aromatase (CYP19A1), estrogen receptor (ER)-α, and ER-β were measured or localized by quantitative real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence. Estrogens were quantified by liquid chromatography/tandem mass spectrometry. All steroidogenic enzymes and estrogen receptors are localized mainly in the superficial layer of the stratified squamous epithelium, blood vessel walls, and muscle fibers of the vagina. Immunolabeling of HSD17B5 and HSD17B12 shows that these enzymes are uniformly distributed from the basal membrane to the superficial keratinized cells, whereas HSD3B1 and aromatase are particularly localized in the outer (external) portion of the epithelial layer. ER-α and ER-β are also distributed within the vaginal epithelium, with expression especially elevated at the basal membrane level. The enzymes responsible for E2 formation as well as ERs are expressed mainly in the superficial layer of the stratified epithelium as well as the muscle layer of the vagina. The present data provide morphologic and biochemical support for the role of local dehydroepiandrosterone transformation into estrogens in regulating epithelial cell maturation, pH, fluid secretion, smooth muscle activity, and blood flow regulation in the primate vagina. Copyright © 2014 Elsevier Inc. All rights reserved.

Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.

PubMed

Wang, Lina; Cheng, Wei; Zhang, Zhimin

2017-07-01

Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and 21 following combined injection, RSV in the lung tissues was assayed by immunohistochemistry, cellular classification was assayed by direct microscopic observation after Wright staining and the secretion of cytokines in the broncho‑alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen type I was assayed by immunofluorescence and western blot analysis. The expression of ER stress related proteins was analyzed by western blot. In addition, the correlations of ER‑stress related proteins with collagen type‑1 were examined. RSV administration resulted in increased inflammation, as demonstrated by increased levels of leukocytes and pro‑inflammatory cytokines in the BALF, and increased collagen type‑1 deposition in the lung tissues of bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV promoted the expression of phosphorylated protein kinase R‑like endoplasmic reticulum kinase (p‑PERK), 78 kDa glucose‑regulated protein (GRP78) and activating transcription factor 6α (ATF6α), which accelerated the severity and process of fibrosis in bleomycin‑induced animal models. The present study provides evidence that RSV infection accelerated the unfolded protein response and bleomycin‑induced lung fibrosis, which may improve our understanding of the pathogenesis of pulmonary fibrosis.

Implementation of parallel moment equations in NIMROD

NASA Astrophysics Data System (ADS)

Lee, Hankyu Q.; Held, Eric D.; Ji, Jeong-Young

2017-10-01

As collisionality is low (the Knudsen number is large) in many plasma applications, kinetic effects become important, particularly in parallel dynamics for magnetized plasmas. Fluid models can capture some kinetic effects when integral parallel closures are adopted. The adiabatic and linear approximations are used in solving general moment equations to obtain the integral closures. In this work, we present an effort to incorporate non-adiabatic (time-dependent) and nonlinear effects into parallel closures. Instead of analytically solving the approximate moment system, we implement exact parallel moment equations in the NIMROD fluid code. The moment code is expected to provide a natural convergence scheme by increasing the number of moments. Work in collaboration with the PSI Center and supported by the U.S. DOE under Grant Nos. DE-SC0014033, DE-SC0016256, and DE-FG02-04ER54746.

From Lawson to Burning Plasmas: a Multi-Fluid Approach

NASA Astrophysics Data System (ADS)

Guazzotto, Luca; Betti, Riccardo

2017-10-01

The Lawson criterion, easily compared to experimental parameters, gives the value for the triple product of plasma density, temperature and energy confinement time needed for the plasma to ignite. Lawson's inaccurate assumptions of 0D geometry and single-fluid plasma model were improved in recent work, where 1D geometry and multi-fluid (ions, electrons and alphas) physics were included in the model, accounting for physical equilibration times and different energy confinement times between species. A much more meaningful analysis than Lawson's for current and future experiment would be expressed in terms of burning plasma state (Q=5, where Q is the ratio between fusion power and heating power). Minimum parameters for reaching Q=5 are calculated based on experimental profiles for density and temperatures and can immediately be compared with experimental performance by defining a no-alpha pressure. This is done in terms of the pressure that the plasma needs to reach for breakeven once the alpha heating has been subtracted from the energy balance. These calculations can be applied to current experiments and future burning-plasma devices. DE-FG02-93ER54215.

Electrostatic separation of superconducting particles from non-superconducting particles and improvement in fuel atomization by electrorheology

NASA Astrophysics Data System (ADS)

Chhabria, Deepika

This thesis has two major topics: (1) Electrostatic Separation of Superconducting Particles from a Mixture of Non-Superconducting Particles. (2) Improvement in fuel atomization by Electrorheology. (1) Based on the basic science research, the interactions between electric field and superconductors, we have developed a new technology, which can separate superconducting granular particles from their mixture with non-superconducting particles. The electric-field induced formation of superconducting balls is important aspect of the interaction between superconducting particles and electric field. When the applied electric field exceeds a critical value, the induced positive surface energy on the superconducting particles forces them to aggregate into balls or cling to the electrodes. In fabrication of superconducting materials, especially HTSC materials, it is common to come across materials with multiple phases: some grains are in superconducting state while the others are not. Our technology is proven to be very useful in separating superconducting grains from the rest non-superconducting materials. To separate superconducting particles from normal conducting particles, we apply a suitable strong electric field. The superconducting particles cling to the electrodes, while normal conducting particles bounce between the electrodes. The superconducting particles could then be collected from the electrodes. To separate superconducting particles from insulating ones, we apply a moderate electric field to force insulating particles to the electrodes to form short chains while the superconducting particles are collected from the middle of capacitor. The importance of this technology is evidenced by the unsuccessful efforts to utilize the Meissner effect to separate superconducting particles from nonsuperconducting ones. Because the Meissner effect is proportional to the particle volume, it has been found that the Meissner effect is not useful when the superconducting particles are smaller than 45mum. One always come across multiphase superconducting materials where most superconducting grains are much smaller than 45mum. On the other hand, since our technology is based on the surface effect, it gets stronger when the particles become smaller. Our technology is thus perfect for small superconducting particles and for fabrication of HTSC materials. The area of superconductivity is expected to be very important for 21 st Century energy industry. The key for this development is the HTSC materials. We, therefore, expect that our technology will have strong impact in the area. (2) Improving engine efficiency and reducing pollutant emissions are extremely important. Here we report our fuel injection technology based on new physics principle that proper application of electrorheology can reduce the viscosity of petroleum fuels. A small device is thus introduced just before the fuel injection for the engine, producing a strong electric field to reduce the fuel viscosity, resulting in much smaller fuel droplets in atomization. As combustion starts at the interface between fuel and air and most harmful emissions are coming from incomplete burning, reducing the size of fuel droplets would increase the total surface area to start burning, leading to a cleaner and more efficient engine. This concept has been widely accepted as the discussions about future engine for efficient and clean combustion are focused on ultra-dilute mixtures at extremely high pressure to produce much finer mist of fuel for combustion. The technology is expected to have broad applications, applicable to current internal combustion engines and future engines as well.

Rhabdomyolysis After Crawling Military Training.

PubMed

Atias-Varon, Danit; Sherman, Haggai; Yanovich, Ran; Heled, Yuval

2017-07-01

Rhabdomyolysis is a syndrome characterized by muscle necrosis followed by release of intracellular muscle contents into the circulation. Exertional rhabdomyolysis (ER) occurs in response to nonfamiliar and/or excessive, prolonged, or repetitive exercises, with eccentric characteristics. In military populations, due to the type of intense, all out physical loads, ER is a significant threat, particularly when training under heat stress. However, many other etiologies exist, and clinical presentations vary greatly. This heterogeneity may result in difficulty in prevention, diagnosis, and return-to-duty decision. The purpose of this report is to point to a new potential risk factor to an extreme muscle breakdown and ER. In this article, we describe three cases of ER in army recruits after strenuous acts of crawling over hard surfaces during an intense military selection process. The soldiers' creatine phosphokinase levels were markedly raised (44,000, 123,500, and 176,599 IU/L), but none of them developed any significant medical complication. There are two major mechanisms leading to ER: the mechanical pathway which is associated with muscle tension, and the metabolic pathway which is associated with cellular energy depletion. During this military selection process, the intensity of the exercises, and cycles of work and rest are highly controlled, and so are the timings of meals and fluids consumption. Moreover, the soldiers were all at least moderately fit and had participated in strenuous exercise events before. According to years of experience with this military selection process, under similar conditions (exercise volumes and loads) we have experienced along the years minimal medical events. At the same time, and this was the unique part in these case, all patients suffered significantly from mechanical injuries caused by crawling on hard surface which were not a part of the planned selection program. Thus, we suggest that the significant muscle breakdown in the presented cases occurred mostly due to crush injury and was not solely a result of the metabolic strain. Thus, we suggest that the extreme creatine phosphokinase levels may be attributed to a synergistic interaction between low-energy trauma, caused by crawling on hard soil and stones, and exertion. We also emphasize the fact that proper physiological support such as proper hydration may assist in prevention of ER complication such as acute renal failure. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading

PubMed Central

Jing, Da; Baik, Andrew D.; Lu, X. Lucas; Zhou, Bin; Lai, Xiaohan; Wang, Liyun; Luo, Erping; Guo, X. Edward

2014-01-01

Osteocytes have been hypothesized to be the major mechanosensors in bone. How in situ osteocytes respond to mechanical stimuli is still unclear because of technical difficulties. In vitro studies have shown that osteocytes exhibited unique calcium (Ca2+) oscillations to fluid shear. However, whether this mechanotransduction phenomenon holds for in situ osteocytes embedded within a mineralized bone matrix under dynamic loading remains unknown. Using a novel synchronized loading/imaging technique, we successfully visualized in real time and quantified Ca2+ responses in osteocytes and bone surface cells in situ under controlled dynamic loading on intact mouse tibia. The resultant fluid-induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was also quantified. Osteocytes, but not surface cells, displayed repetitive Ca2+ spikes in response to dynamic loading, with spike frequency and magnitude dependent on load magnitude, tissue strain, and shear stress in the LCS. The Ca2+ oscillations were significantly reduced by endoplasmic reticulum (ER) depletion and P2 purinergic receptor (P2R)/phospholipase C (PLC) inhibition. This study provides direct evidence that osteocytes respond to in situ mechanical loading by Ca2+ oscillations, which are dependent on the P2R/PLC/inositol trisphosphate/ER pathway. This study develops a novel approach in skeletal mechanobiology and also advances our fundamental knowledge of bone mechanotransduction.—Jing, D., Baik, A. D., Lu, X. L., Zhou, B., Lai, X., Wang, L., Luo, E., Guo, X. E. In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading. PMID:24347610

Characterizing Droplet Formation from Non-Linear Slosh in a Propellant Tank

NASA Technical Reports Server (NTRS)

Brodnick, Jacob; Yang, Hong; West, Jeffrey

2015-01-01

The Fluid Dynamics Branch (ER42) at the Marshall Space Flight Center (MSFC) was tasked with characterizing the formation and evolution of liquid droplets resulting from nonlinear propellant slosh in a storage tank. Lateral excitation of propellant tanks can produce high amplitude nonlinear slosh waves through large amplitude excitations and or excitation frequencies near a resonance frequency of the tank. The high amplitude slosh waves become breaking waves upon attaining a certain amplitude or encountering a contracting geometry such as the upper dome section of a spherical tank. Inherent perturbations in the thinning regions of breaking waves result in alternating regions of high and low pressure within the fluid. Droplets form once the force from the local pressure differential becomes larger than the force maintaining the fluid interface shape due to surface tension. Droplets released from breaking waves in a pressurized tank may lead to ullage collapse given the appropriate conditions due to the increased liquid surface area and thus heat transfer between the fluids. The goal of this project is to create an engineering model that describes droplet formation as a function of propellant slosh for use in the evaluation of ullage collapse during a sloshing event. The Volume of Fluid (VOF) model in the production level Computational Fluid Dynamics (CFD) code Loci-Stream was used to predict droplet formation from breaking waves with realistic surface tension characteristics. Various excitation frequencies and amplitudes were investigated at multiple fill levels for a single storage tank to create the engineering model of droplet formation from lateral propellant slosh.

High temperature hydrothermal synthesis of rare-earth titanates: synthesis and structure of RE5Ti4O15(OH) (RE = La, Er), Sm3TiO5(OH)3, RE5Ti2O11(OH) (RE = Tm-Lu) and Ce2Ti4O11.

PubMed

Fulle, Kyle; Sanjeewa, Liurukara D; McMillen, Colin D; Kolis, Joseph W

2018-05-15

Reactions of rare-earth oxides with TiO2 were performed in high temperature (650-700 °C) hydrothermal fluids. Two different mineralizer fluids were examined, 20 M KOH and 30 M CsF, and their respective products analyzed. When concentrated KOH fluids were used, single crystals of a variety of new OH- containing species were isolated and structurally characterized: RE5Ti4O15(OH) (RE = La, Er) I, Sm3TiO5(OH)3II and RE5Ti2O11(OH) (RE = Tm-Lu) III. La5Ti4O15(OH) I crystallizes in the orthorhombic space group Pnnm with unit cell dimensions of a = 30.5152(12) Å, b = 5.5832(2) Å, c = 7.7590(3) Å and V = 1321.92(9) Å3, Z = 4. Sm3TiO5(OH)3II crystallizes in the monoclinic space group P21/m with unit cell parameters of a = 5.6066(2) Å, b = 10.4622(4) Å, c = 6.1258(2) Å and β = 104.7390(10)°, V = 347.50(2) Å3, Z = 2. Lu5Ti2O11(OH) III crystallizes in the monoclinic space group C2/m with unit cell dimensions of a = 12.1252(9) Å, b = 5.8243(4) Å, c = 7.0407(5) Å, β = 106.939(3)° and V = 475.65(6) Å3, Z = 2. When concentrated fluoride solutions are used, mostly RE2Ti2O7 type compounds were isolated in either cubic or monoclinic phases. In the case of cerium, Ce2Ti4O11IV was isolated that crystallizes in the monoclinic space group C2/c with unit cell parameters of a = 13.6875(7) Å, b = 5.0955(3) Å, c = 12.8592(7) Å, β = 108.964(2)° and V = 848.18(8) Å3, Z = 4. The synthesis, structural characterization, and supporting characterization are reported for all compounds. The work highlights the complementary nature of hydroxide and fluoride fluids in studying the reactivity of refractory oxides.

Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein-coupled estrogen receptor.

PubMed

Bouskine, Adil; Nebout, Marielle; Brücker-Davis, Françoise; Benahmed, Mohamed; Fenichel, Patrick

2009-07-01

Fetal exposure to environmental estrogens may contribute to hypofertility and/or to testicular germ cell cancer. However, many of these xenoestrogens have only a weak affinity for the classical estrogen receptors (ERs,) which is 1,000-fold less potent than the affinity of 17beta-estradiol (E(2)). Thus, several mechanisms have been suggested to explain how they could affect male germ cell proliferation at low environmental relevant concentrations. In this study we aimed to explore the possible promoting effect of bisphenol A (BPA) on human testicular seminoma cells. BPA is a well-recognized estrogenic endocrine disruptor used as a monomer to manufacture poly carbonate plastic and released from resin-lined food or beverage cans or from dental sealants. BPA at very low concentrations (10(-9) to 10(-12) M) similar to those found in human fluids stimulated JKT-1 cell proliferation in vitro. BPA activated both cAMP-dependent protein kinase and cGMP-dependent protein kinase pathways and triggered a rapid (15 min) phosphorylation of the transcription factor cAMP response-element-binding protein (CREB) and the cell cycle regulator retinoblastoma protein (Rb). This nongenomic activation did not involve classical ERs because it could not be reversed by ICI 182780 (an ER antagonist) or reproduced either by E(2) or by diethylstilbestrol (a potent synthetic estrogen), which instead triggered a suppressive effect. This activation was reproduced only by E(2) coupled to bovine serum albumin (BSA), which is unable to enter the cell. As with E(2)-BSA, BPA promoted JKT-1 cell proliferation through a G-protein-coupled nonclassical membrane ER (GPCR) involving a Galpha(s) and a Galpha(i)/Galpha(q) subunit, as shown by the reversible effect observed by the corresponding inhibitors NF449 and pertussis toxin. This GPCR-mediated nongenomic action represents--in addition to the classical ER-mediated effect--a new basis for evaluating xenoestrogens such as BPA that, at low doses and with a high affinity for this GPCR, could interfere with the developmental programming of fetal germ cell proliferation and/or differentiation when they cross the placenta.

Application of lasers in endodontics

NASA Astrophysics Data System (ADS)

Ertl, Thomas P.; Benthin, Hartmut; Majaron, Boris; Mueller, Gerhard J.

1997-12-01

Root canal treatment is still a problem in dentistry. Very often the conventional treatment fails and several treatment sessions are necessary to save the tooth from root resection or extraction. Application of lasers may help in this situation. Bacteria reduction has been demonstrated both in vitro and clinically and is either based on laser induced thermal effects or by using an ultraviolet light source. Root canal cleansing is possible by Er:YAG/YSGG-Lasers, using the hydrodynamic motion of a fluid filled in the canals. However root canal shaping using lasers is still a problem. Via falsas and fiber breakage are points of research.

An Experimental Investigation of the Acoustic and Fluid Dynamic Characteristics of a Circulation-Controlled Airfoil

DTIC Science & Technology

2011-05-13

1, and the complex velocity for the image ellipse is given by Wafoi) UXR 2 4 iT \\ 1 27T22 )l~4’ (24) 3 Substituting zfc = 21 - 2ihc and...evolution of the How and its various length and velocity scales. Such a finding would have direct application to Howe’s model and also the design of...of less than 2% . ^= 0.0085 (C^er) 0184 (55) It should be noted that Equation 55 appears to be only applicable to the airfoil geometry of the

The neoclassical ``Electron Root'' feature in the Wendelstein-7-AS stellarator

NASA Astrophysics Data System (ADS)

Maaßberg, H.; Beidler, C. D.; Gasparino, U.; Romé, M.; Dyabilin, K. S.; Marushchenko, N. B.; Murakami, S.

2000-01-01

The neoclassical prediction of the "electron root," i.e., a strongly positive radial electric field, Er (being the solution of the ambipolarity condition of the particle fluxes), is analyzed for low-density discharges in Wendelstein-7-AS [G. Grieger, W. Lotz, P. Merkel, et al., Phys. Fluids B 4, 2081 (1992)]. In these electron cyclotron resonance heated (ECRH) discharges with highly localized central power deposition, peaked Te profiles [with Te(0) up to 6 keV and with Ti≪Te] and strongly positive Er in the central region are measured. It is shown that this "electron root" feature at W7-AS is driven by ripple-trapped suprathermal electrons generated by the ECRH. The fraction of ripple-trapped particles in the ECRH launching plane, which can be varied at W7-AS, is found to be the most important. After switching off the heating the "electron root" feature disappears nearly immediately, i.e., two different time scales for the electron temperature decay in the central region are observed. Monte Carlo simulations in five-dimensional phase space are presented, clearly indicating that the additional "convective" electron fluxes driven by the ECRH are of the same order as the ambipolar neoclassical prediction for the "ion root" at much lower Er. For the predicted "electron root," the ion fluxes calculated based on the traditional neoclassical ordering are much too small; shortcomings of the usual approach are indentified and a new ordering scheme is proposed.

Scaling of the stochastic broadening from low mn, high mn, and peeling-ballooning magnetic perturbations in the DIII-D tokamak

NASA Astrophysics Data System (ADS)

Zhao, Michael; Punjabi, Alkesh; Ali, Halima

2009-11-01

The equilibrium EFIT data for the DIII-D shot 115467 is used to construct the equilibrium generating function for magnetic field line trajectories in the DIII-D tokamak in natural canonical coordinates [A. Punjabi, and H. Ali, Phys. Plasmas 15, 122502 (2008)]. A canonical transformation is used to construct an area-preserving map for field line trajectories in the natural canonical coordinates in the DIII-D. Maps in natural canonical coordinates have the advantage that natural canonical coordinates can be inverted to calculate real space coordinates (R,Z,φ), and there is no problem in crossing the separatrix. This is not possible for magnetic coordinates [O. Kerwin, A. Punjabi, and H. Ali, Phys. Plasmas 15, 072504 (2008)]. This map is applied to calculate stochastic broadening from the low mn (m,n)=(1,1)+(1,-1); high mn (m,n)=(4,1)+(3,1); and the peeling-ballooning (m,n)=(40,10)+(30,10) magnetic perturbations. In all three cases, the scaling of the widths of stochastic layer near the X-point in the principal plane of the DIII-D deviates at most by 6% from the .5ex1 -.1em/ -.15em.25ex2 power Boozer-Rechester scaling [A. Boozer, and A. Rechester, Phys. Fluids 21, 682 (1978)]. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793.

A recombinant estrogen receptor fragment-based homogeneous fluorescent assay for rapid detection of estrogens.

PubMed

Wang, Dan; Xie, Jiangbi; Zhu, Xiaocui; Li, Jinqiu; Zhao, Dongqin; Zhao, Meiping

2014-05-15

In this work, we demonstrate a novel estrogenic receptor fragment-based homogeneous fluorescent assay which enables rapid and sensitive detection of 17β-estradiol (E2) and other highly potent estrogens. A modified human estrogenic receptor fragment (N-His × 6-hER270-595-C-Strep tag II) has been constructed that contains amino acids 270-595 of wild-type human estrogenic receptor α (hER270-595) and two specific tags (6 × His and Strep tag II) fused to the N and C terminus, respectively. The designed receptor protein fragment could be easily produced by prokaryotic expression with high yield and high purity. The obtained protein exhibits high binding affinity to E2 and the two tags greatly facilitate the application of the recombinant protein. Taking advantage of the unique spectroscopic properties of coumestrol (CS), a fluorescent phytoestrogen, a CS/hER270-595-based fluorescent assay has been developed which can sensitively respond to E2 within 1.0 min with a linear working range from 0.1 to 20 ng/mL and a limit of detection of 0.1 ng/mL. The assay was successfully applied for rapid detection of E2 in the culture medium of rat hippocampal neurons. The method also holds great potential for high-throughput monitoring the variation of estrogen levels in complex biological fluids, which is crucial for investigation of the molecular basis of various estrogen-involved processes. Copyright © 2013 Elsevier B.V. All rights reserved.

Energy variational analysis of ions in water and channels: Field theory for primitive models of complex ionic fluids

PubMed Central

Eisenberg, Bob; Hyon, YunKyong; Liu, Chun

2010-01-01

Ionic solutions are mixtures of interacting anions and cations. They hardly resemble dilute gases of uncharged noninteracting point particles described in elementary textbooks. Biological and electrochemical solutions have many components that interact strongly as they flow in concentrated environments near electrodes, ion channels, or active sites of enzymes. Interactions in concentrated environments help determine the characteristic properties of electrodes, enzymes, and ion channels. Flows are driven by a combination of electrical and chemical potentials that depend on the charges, concentrations, and sizes of all ions, not just the same type of ion. We use a variational method EnVarA (energy variational analysis) that combines Hamilton’s least action and Rayleigh’s dissipation principles to create a variational field theory that includes flow, friction, and complex structure with physical boundary conditions. EnVarA optimizes both the action integral functional of classical mechanics and the dissipation functional. These functionals can include entropy and dissipation as well as potential energy. The stationary point of the action is determined with respect to the trajectory of particles. The stationary point of the dissipation is determined with respect to rate functions (such as velocity). Both variations are written in one Eulerian (laboratory) framework. In variational analysis, an “extra layer” of mathematics is used to derive partial differential equations. Energies and dissipations of different components are combined in EnVarA and Euler–Lagrange equations are then derived. These partial differential equations are the unique consequence of the contributions of individual components. The form and parameters of the partial differential equations are determined by algebra without additional physical content or assumptions. The partial differential equations of mixtures automatically combine physical properties of individual (unmixed) components. If a new component is added to the energy or dissipation, the Euler–Lagrange equations change form and interaction terms appear without additional adjustable parameters. EnVarA has previously been used to compute properties of liquid crystals, polymer fluids, and electrorheological fluids containing solid balls and charged oil droplets that fission and fuse. Here we apply EnVarA to the primitive model of electrolytes in which ions are spheres in a frictional dielectric. The resulting Euler–Lagrange equations include electrostatics and diffusion and friction. They are a time dependent generalization of the Poisson–Nernst–Planck equations of semiconductors, electrochemistry, and molecular biophysics. They include the finite diameter of ions. The EnVarA treatment is applied to ions next to a charged wall, where layering is observed. Applied to an ion channel, EnVarA calculates a quick transient pile-up of electric charge, transient and steady flow through the channel, stationary “binding” in the channel, and the eventual accumulation of salts in “unstirred layers” near channels. EnVarA treats electrolytes in a unified way as complex rather than simple fluids. Ad hoc descriptions of interactions and flow have been used in many areas of science to deal with the nonideal properties of electrolytes. It seems likely that the variational treatment can simplify, unify, and perhaps derive and improve those descriptions. PMID:20849161

Simulation of the formation of nonequilibrium structures in magnetorheological fluids subject to an external magnetic field

NASA Astrophysics Data System (ADS)

Mohebi, M.; Jamasbi, N.; Liu, Jing

1996-11-01

We developed a computer model to understand the nonequilibrium structures induced in a magnetorheological (MR) fluid by rapidly applying an external magnetic field. MR fluids consist of particles suspended in a liquid where particles interact through dipole moments induced by the external magnetic field. We have simulated these induced structures in both directions, parallel and perpendicular to the field, in the limit of fastest response, by neglecting thermal motion and applying the field instantaneously. Our results show that the process of structure formation starts with particles forming chains aligned with the external field. The chains then coalesce to form columns and wall-like structures (``worms'' as viewed from the top). The complexity of this pattern is found to depend on the concentration of particles and the confinement of the cell in the direction of the external field. These results are consistent with experimental observations [G.A. Flores et al., in Proceedings of the Fifth International Conference on ER Fluids, MR Suspensions, and Associate Technology, University of Sheffield, Sheffield, 1995, edited by W. Bullough (World Scientific, Singapore, 1996), p. 140]. We have also used this model to study the interaction of two chains. The results of this study help in the understanding of the connection between the thickness of the sample and the increased complexity of the observed lateral pattern.

Deformation in the Basin & Range Province and Rio Grande Rift using InSAR Time Series

NASA Astrophysics Data System (ADS)

Taylor, H.; Pisaniello, M.; Pritchard, M. E.

2012-12-01

High heat flow in the Basin and Range Province and Rio Grande Rift has been attributed to partial melting in the crust and upper mantle as a result of ongoing extension (e.g. Lachenbruch 1978). We would then expect to observe surface deformation in areas with actively moving magmatic fluids. The distribution of these magmatic fluids has implications for the rheology of the crust and upper mantle. For this study, we use InSAR to locate deformation due to magmatic sources as well as localized hydrologic deformation. While our focus is magmatic deformation, hydrologic signals are important for correcting geodetic data used to monitor tectonic activity. InSAR is a suitable technique for a large study in the Basin and Range and Rio Grande Rift since SAR acquisitions are both numerous and temporally extensive in these regions. We use ERS-1, ERS-2, and ENVISAT SAR images from 1992-2010 to create time series' with interferograms up to 1800km long from both ascending and descending satellite tracks. Each time series has an average of 100 interferograms reducing the atmospheric noise that masks small deformation signals in single interferograms. The time series' results are validated using overlapping tracks and are further compared to signals identified in previous geophysical studies (e.g. Reilinger and Brown 1980, Massonnet et al 1997, Finnegan and Pritchard 2009). We present results for several areas of deformation in the Basin & Range Province and Rio Grande Rift. An agricultural area near Roswell, NM exhibits seasonal uplift and subsidence of ±3.5cm/yr between 1992 and 1999. Results indicate subsidence on the order of 1cm/yr and uplift of 2cm/yr at the Raft River power plant, ID that is likely related to the start of geothermal fluid production and injection. Just north of the Raft River plant, we detect what appears to be rapid agricultural subsidence in an area extending for 50km. We discuss subsidence of ~2cm/yr in Escalante Valley, UT that is comparable to deformation observed in an earlier InSAR study on subsidence caused by ground-water withdrawal (Forster, 2006).

Expression pattern of G protein‑coupled estrogen receptor 1 (GPER) in human cumulus granulosa cells (CGCs) of patients with PCOS.

PubMed

Zang, Lili; Zhang, Quan; Zhou, Yi; Zhao, Yan; Lu, Linlin; Jiang, Zhou; Peng, Zhen; Zou, Shuhua

2016-06-01

Estradiol mediates its actions by binding to classical nuclear receptors, estrogen receptor α (ER-α) and estrogen receptor β (ER-β), and the non-classical G protein-coupled estrogen receptor 1(GPER). Several gene knockdown models have shown the importance of the receptors for growth of the oocyte and for ovulation. The aim of our study was to identify the pattern of GPER expression in human cumulus granulosa cells (CGCs) from ovarian follicles at different stages of oocyte maturation, and the differences of GPER expression between polycystic ovary syndrome (PCOS) patients and non-PCOS women. Thirty-eight cases of PCOS patients and a control group of thirty-two infertile women without PCOS were used in this study. GPER's location in CGCs was investigated by immunohistochemistry. Quantitative RT-PCR and western blot were used to identify the quantify GPER expression. Here we demonstrated that GPER was expressed in CGCs of both PCOS patients and non-PCOS women, and the expression of GPER was decreased significantly during oocyte maturation. But the expression levels of GPER in CGCs of PCOS patients and non-PCOS women were not significantly different. The data indicate that GPER may play a role during human oocyte maturation through its action in cumulus granulosa cells. AMHRIIs: anti-Mullerian hormone type II receptors; BMI: body mass index; CGCs: cumulus granulosa cells; COH: controlled ovarian hyperstimulation; E2: estradiol; EGFR: epidermal growth factor receptor; ER-α: estrogen receptor; ER-β: estrogen receptor β; FF: follicular fluid; FSH: follicle-stimulating hormone; GCs: granulosa cells; GPER: G protein-coupled estrogen receptor 1; GV: germinal vesicle; GVBD: germinal vesicle breakdown; HCG: human chorionic gonadotropin; IRS: immunoreactive score; IVF-ET: in vitro fertilization and embryo transfer; MI: metaphase I; MII: metaphase II; MAPK: mitogen-activated protein kinase; OCCCs: oocyte corona cumulus complexes; PCOS: polycystic ovarian syndrome; q quantitative real-time PCR: qRT-PCR.

Recent progress in the growth and applications of graphene as a smart material: A review

NASA Astrophysics Data System (ADS)

Aissa, Brahim; Memon, Nasir; Ali, Adnan; Khraisheh, Marwan

2015-09-01

Innovative breakthroughs in fundamental research and industrial applications of graphene material have made its mass and low-cost production a necessary step toward its real world applications. This one-atom thick crystal of carbon, gathers a set of unique physico-chemical properties, ranging from its extreme mechanical behavior to its exceptional electrical and thermal conductivities, which are making graphene as a serious alternative to replace many conventional materials for various applications. In this review paper, we highlight the most important experimental results on the synthesis of graphene material, its emerging properties with reference to its smart applications. We discuss the possibility to successfully integrating graphene directly into device, enabling thereby the realization of a wide range of applications, including actuation, photovoltaic, thermoelectricity, shape memory, self-healing, electrorheology and space missions. The future outlook of graphene is also considered and discussed.

Reverse Electrorheological Effect:. a Suspension of Colloidal Motors

NASA Astrophysics Data System (ADS)

Lemaire, E.; Lobry, L.

We present an experimental evidence of a "colloidal motor" behavior of a suspension. Previous attempts to observe such a phenomenon with ferrofluids under alternating magnetic fields have failed. Here, negative viscosity is obtained by making use of Quincke rotation: the spontaneous rotation of insulating particles suspended in a weakly conducting liquid when the system is submitted to a DC electric field. In such a case, particles rotate around any axis perpendicular to the applied field, nevertheless, when a velocity gradient (simple shear rate) is applied along the E field direction, the particles rotation axes will be favored in the vorticity direction (the direction perpendicular to the suspension velocity and the velocity gradient). The collective movement of particles drives the surrounding liquid and then leads to a reduction of the apparent viscosity of the suspension. The decrease in viscosity is sufficiently important for the liquid to flow while no submitted to any mechanical stress.

Changes in the Healthy Beverage Index in Response to an Intervention Targeting a Reduction in Sugar-Sweetened Beverage Consumption as Compared to an Intervention Targeting Improvements in Physical Activity: Results from the Talking Health Trial.

PubMed

Hedrick, Valisa E; Davy, Brenda M; Myers, Emily A; You, Wen; Zoellner, Jamie M

2015-12-04

The recently developed Healthy Beverage Index (HBI) was designed to evaluate overall beverage intake quality (including total fluid consumption and beverage calories), yet no known intervention studies have assessed longitudinal changes to the HBI. The objective of this investigation was to assess changes in HBI scores in response to a sugar-sweetened beverage (SSB) reduction trial as compared to a physical activity comparison group. Participants were enrolled into a six-month, community-based, controlled behavioral trial and randomized into either a SSB reduction group (SIPsmartER) or a physical activity group (MoveMore). Correlations and multilevel mixed-effects linear regression with intention-to-treat analyses are presented. Total HBI score significantly increased for SIPsmartER (n = 149) (mean increase = 7.5 points (5.4, 9.7), p ≤ 0.001) and MoveMore (n = 143) (mean increase = 3.4 points (1.6, 5.2), p ≤ 0.001) participants, with a significant between group effect (p ≤ 0.05), over the six-month intervention. Other significant changes in HBI components for SIPsmartER included increased SSB and total beverage calorie scores, and decreased low-fat milk and diet soda scores. Changes in total HBI scores were significantly correlated with changes in total Healthy Eating Index-2010 scores (r = 0.15, p ≤ 0.01). Our findings suggest that individual HBI component scores, beyond the SSB component, are influenced by intervention strategies that primarily focus on SSB reduction.

Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract.

PubMed

O'Connell, Fionnuala P; Wang, Helen H; Odze, Robert D

2005-03-01

Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma. To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas. Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas. Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P = .009, and P < .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups. Estrogen receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are helpful in distinguishing primary gastric carcinomas from metastatic breast carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific for primary gastric carcinomas.

Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

PubMed

Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

2018-05-08

Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

Treatment with 17-allylamino-17-demethoxygeldanamycin ameliorated symptoms of Bartter syndrome type IV caused by mutated Bsnd in mice.

PubMed

Nomura, Naohiro; Kamiya, Kazusaku; Ikeda, Katsuhisa; Yui, Naofumi; Chiga, Motoko; Sohara, Eisei; Rai, Tatemitu; Sakaki, Sei; Uchida, Shinich

2013-11-22

Mutations of BSND, which encodes barttin, cause Bartter syndrome type IV. This disease is characterized by salt and fluid loss, hypokalemia, metabolic alkalosis, and sensorineural hearing impairment. Barttin is the β-subunit of the ClC-K chloride channel, which recruits it to the plasma membranes, and the ClC-K/barttin complex contributes to transepithelial chloride transport in the kidney and inner ear. The retention of mutant forms of barttin in the endoplasmic reticulum (ER) is etiologically linked to Bartter syndrome type IV. Here, we report that treatment with 17-allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, enhanced the plasma membrane expression of mutant barttins (R8L and G47R) in Madin-Darby canine kidney cells. Administration of 17-AAG to Bsnd(R8L/R8L) knock-in mice elevated the plasma membrane expression of R8L in the kidney and inner ear, thereby mitigating hypokalemia, metabolic alkalosis, and hearing loss. These results suggest that drugs that rescue ER-retained mutant barttin may be useful for treating patients with Bartter syndrome type IV. Copyright © 2013 Elsevier Inc. All rights reserved.

HNF4A expression as a potential diagnostic tool to discriminate primary gastric cancer from breast cancer metastasis in a Brazilian cohort.

PubMed

Jucá, Patrícia Chaves de Freitas Campos; Corrêa, Stephany; Vignal, Giselle Maria; Accioly, Maria Theresa de Souza; Lustosa, Suzana Angélica Silva; Abdelhay, Eliana; Matos, Delcio

2017-06-05

Among the many challenges in cancer diagnosis is the early distinction between metastatic cancer and a secondary tumor. This difficulty stems from the lack of markers that offer high sensitivity and specificity and can be easily applied in routine laboratory work. An example of this challenge is distinguishing gastric metastases originating from breast cancer from a gastric primary tumor. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of this study was to analyze the expression of HNF4A, estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein 15 (GCDFP-15) in a Brazilian cohort. We performed immunohistochemistry analysis of HNF4A, ER, PR and GCDFP-15 in 126 patients divided into three cohorts: primary breast cancer, primary gastric cancer and both types of tumors. Our data confirmed the sensitivity and specificity of the HNF4A marker compared to other currently used clinical markers. HNF4A alone could be a gold standard marker for distinguishing primary gastric cancer from breast metastasis, thus validating its potential clinical use, especially in populations with high genetic diversity.

Seismic Characterizations of Fractures: Dynamic Diagnostics

NASA Astrophysics Data System (ADS)

Pyrak-Nolte, L. J.

2017-12-01

Fracture geometry controls fluid flow in a fracture, affects mechanical stability and influences energy partitioning that affects wave scattering. Our ability to detect and monitor fracture evolution is controlled by the frequency of the signal used to probe a fracture system, i.e. frequency selects the scales. No matter the frequency chosen, some set of discontinuities will be optimal for detection because different wavelengths sample different subsets of fractures. The select subset of fractures is based on the stiffness of the fractures which in turn is linked to fluid flow. A goal is obtaining information from scales outside the optimal detection regime. Fracture geometry trajectories are a potential approach to drive a fracture system across observation scales, i.e. moving systems between effective medium and scattering regimes. Dynamic trajectories (such as perturbing stress, fluid pressure, chemical alteration, etc.) can be used to perturb fracture geometry to enhance scattering or give rise to discrete modes that are intimately related to the micro-structural evolution of a fracture. However, identification of these signal features will require methods for identifying these micro-structural signatures in complicated scattered fields. Acknowledgment: This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Geosciences Research Program under Award Number (DE-FG02-09ER16022).

77 FR 60978 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

...-006; ER10- 2674-006; ER10-2675-007; ER10-2676-006; ER10-2677-006; ER10-2678-005; ER10-3319-008; ER11... 10/18/12. Docket Numbers: ER12-2312-002. Applicants: Perigee Energy, LLC. Description: Perigee Energy...

Rab7a modulates ER stress and ER morphology.

PubMed

Mateus, Duarte; Marini, Elettra Sara; Progida, Cinzia; Bakke, Oddmund

2018-05-01

The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress. Indeed, inhibition of Rab7a expression by siRNA or expression of the dominant negative mutant Rab7aT22 N, leads to enlargement of sheet-like ER structures and spreading towards the cell periphery. Notably, such alterations are ascribable neither to a direct modulation of the ER shaping proteins Reticulon-4b and CLIMP63, nor to interactions with Protrudin, a Rab7a-binding protein known to affect the ER organization. Conversely, depletion of Rab7a leads to basal ER stress, in turn causing ER membrane expansion. Both ER enlargement and basal ER stress are reverted in rescue experiments by Rab7a re-expression, as well as by the ER chemical chaperone tauroursodeoxycholic acid (TUDCA). Collectively, these findings reveal a new role of Rab7a in ER homeostasis, and indicate that genetic and pharmacological ER stress manipulation may restore ER morphology in Rab7a silenced cells. Copyright © 2018 Elsevier B.V. All rights reserved.

75 FR 39225 - Combined Notice of Filings No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

... Date: 5 p.m. Eastern Time on Thursday, July 15, 2010. Docket Numbers: ER05-1389-000; ER07-301-000; ER07.... Eastern Time on Wednesday, July 14, 2010. Docket Numbers: ER07-844-007; ER07-845-007; ER07-846-007; ER07-847- 007; ER09-629-007; ER99-4160-023. Applicants: Dynegy Power Marketing, Inc., Dynegy Moss Landing...

Contrasted monazite hydrothermal alteration mechanisms and their geochemical implications

NASA Astrophysics Data System (ADS)

Poitrasson, Franck; Chenery, Simon; Bland, David J.

1996-12-01

In spite of the major importance of monazite as a repository for the rare earths and Th in the continental crust, for U-Th-Pb geochronology, and as a possible form for high-level nuclear waste, very little work has been carried out so far on the behaviour of this mineral during fluid-rock events. This contribution describes two contrasting examples of the hydrothermal alteration of monazite. The first case comes from a sample of the Carnmenellis granite (Cornwall, Southwest England), chloritized at 284 ± 16°C, whereas the other occurs in the Skiddaw granite (Lake District, Northwest England), which underwent greisenization at 200 ± 30°C. An integrated study involving backscattered scanning electron microscopy, electron microprobe analyses, and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) reveals that the chloritization event was characterized by the coupled substitution 2REE 3+ ⇌ Th 4+ + Ca 2+ in the altered parts of the monazite, thus leaving the P-O framework of the crystal untouched. In contrast, greisenization led to the coupled substitution REE 3+ + P 5+ ⇌ Th 4+ + Si 4+, and therefore involved a partial destruction of the phosphate framework. The resulting rare earth element patterns are quite different for these two examples, with a maximum depletion for Dy and Er in the altered parts of the Carnmenellis monazite, whereas the Skiddaw monazite shows a light rare earth depletion but an Yb and Er enrichment during alteration. This latter enrichment, accompanied by an increase in U but roughly unchanged Pb concentrations, probably resulted from a decrease in the size of the 9-coordinated site in monazite, thereby favouring the smaller rare earths. These contrasted styles of monazite alteration show that the conditions of fluid-rock interaction will not only affect the aqueous geochemistry of the lanthanides, actinides and lead, and the relative stability of the different minerals holding these elements. Variations in these conditions will also lead to various possible chemical exchanges between the crystalline phases and the hydrothermal fluids. The occurrence of common lead along penetrative cracks in the Carnmenellis monazite shows that only a leaching, prior to the U-Pb analyses of the whole-grain, will permit an accurate determination of the magmatic crystallization age. In contrast, for the Skiddaw case it may be possible to date the fluid-rock event by in situ 207Pb/ 206Pb geochronology. The observation that the altered parts of both monazite examples display Nd leaching and no significant Sm/Nd fractionation indicates that they should not affect the host whole-rock Nd isotopic signatures. Finally, it appears that monazite-like ceramics designed for the containment of high-level nuclear wastes will retain Th and the geochemically equivalent transuranic elements during fluid-rock events similar to those documented in this study but may release Nd, U and the corresponding radionuclides to the environment.

Modeling Fluid-Structure Interaction in ANSYS Workbench

DTIC Science & Technology

2016-08-31

IB U TI O N S TA TE M EN T A .A pp ro ve d fo rp ub lic re le as e; di st rib...Q R M Si er ra L ob o, In c. M od el in g Fl ui d- St ru ct ur e In te ra ct io n in A N SY S W or kb en ch 31 A ug us t 2 01 6 2 D IS TR IB ...S) G ro up 3 D IS TR IB U TI O N S TA TE M EN T A .A pp ro ve d fo rp ub lic re le as e; di st rib

Combustion-Derived Nanoparticles in Key Brain Target Cells and Organelles in Young Urbanites: Culprit Hidden in Plain Sight in Alzheimer's Disease Development.

PubMed

González-Maciel, Angélica; Reynoso-Robles, Rafael; Torres-Jardón, Ricardo; Mukherjee, Partha S; Calderón-Garcidueñas, Lilian

2017-01-01

Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains. Using transmission electron microscopy, we documented CDNPs in neurons, glia, choroid plexus, and neurovascular units of young MC residents versus matched clean air controls. CDNPs are associated with pathology in mitochondria, endoplasmic reticulum (ER), mitochondria-ER contacts (MERCs), axons,and dendrites. There is a significant difference in size and numbers between spherical CDNPs (>85%) and the angular, euhedral endogenous NPs (<15%). Spherical CDNPs (dogs 21.2±7.1 nm in diameter versus humans 29.1±11.2 nm, p = 0.002) are present in neurons, glia, choroid plexus, endothelium, nasal and olfactory epithelium, and in CSF at significantly higher in numbers in MC residents (p < 0.0001). Degenerated MERCs, abnormal mitochondria, and dilated ER are widespread, and CDNPs in close contact with neurofilaments, glial fibers, and chromatin are a potential source for altered microtubule dynamics, mitochondrial dysfunction, accumulation and aggregation of unfolded proteins, abnormal endosomal systems, altered insulin signaling, calcium homeostasis, apoptotic signaling, autophagy, and epigenetic changes. Highly oxidative, ubiquitous CDNPs constitute a novel path into AD pathogenesis. Exposed children and young adults need early neuroprotection and multidisciplinary prevention efforts to modify the course of AD at early stages.

Technical report for a fluidless directional drilling system demonstrated at Solid Waste Storage Area 6 shallow buried waste sites

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

NONE

The purpose of the research was to demonstrate a fluidless directional drilling and monitoring system (FDD) specifically tailored to address environmental drilling concerns for shallow buried wasted. The major concerns are related to worker exposure, minimizing waste generation, and confining the spread of contamination. The FDD is potentially applicable to Environmental Restoration (ER) activities for the Oak Ridge National Laboratory Waste Area Grouping 6 (WAG 6) shallow buried waste disposed in unlined trenches. Major ER activities for directional drilling are to develop a drilling system for leachate collection directly beneath trenches, and to provide localized control over leachate release tomore » the environment. Other ER FDD activities could include vadose zone and groundwater monitoring of contaminant transport. The operational constraints pointed the research in the direction of purchasing a steerable impact hammer, or mole, manufactured by Steer-Rite Ltd. of Racine, Wisconsin. This drill was selected due to the very low cost ($25,000) associated with procuring the drill, steering module, instrumentation and service lines. The impact hammer is a self propelled drill which penetrates the soil by compacting cut material along the sidewalls of the borehole. Essentially, it forces its way through the subsurface. Although the pneumatic hammer exhausts compressed air which must be handled at the borehole collar, it does not generate soil cuttings or liquids. This is the basis for the term fluidless. A stub casing muffler was attached to the entrance hole for controlling exhaust gas and any airborne releases. Other environmental compliance modifications made to the equipment included operating the tool without lubrication, and using water instead of hydraulic fluid to actuate the steering fins on the tool.« less

Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System

PubMed Central

Bugel, Sean M.; Bonventre, Josephine A.; Tanguay, Robert L.

2016-01-01

Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay—an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos were exposed to 1–50 µM of each chemical from 6 to 120 h postfertilization (hpf), and assessed for 26 adverse developmental endpoints at 24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR) assay. Gene expression was comparatively evaluated for all compounds for effects on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb, vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects on one or more of the developmental or behavioral endpoints. Hierarchical clustering and principle component analyses compared toxicity profiles and identified 3 distinct groups of bioactive flavonoids. Despite robust induction of multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists did not ameliorate toxicity, suggesting ER-independence and alternative modes of action. Taken together, these studies demonstrate that development is sensitive to perturbation by bioactive flavonoids in zebrafish that are not related to traditional estrogen receptor mode of action pathways. This integrative zebrafish platform provides a useful framework for evaluating flavonoid developmental toxicity and hazard prioritization. PMID:27492224

Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions.

PubMed

Lew, Madelyn; Pang, Judy C; Jing, Xin; Fields, Kristina L; Roh, Michael H

2015-10-01

It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions. © 2015 American Cancer Society.

Essential role of carbonic anhydrase XII in secretory gland fluid and HCO3 (-) secretion revealed by disease causing human mutation.

PubMed

Hong, Jeong Hee; Muhammad, Emad; Zheng, Changyu; Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta; Parvari, Ruti; Muallem, Shmuel

2015-12-15

Fluid and HCO3 (-) secretion is essential for all epithelia; aberrant secretion is associated with several diseases. Carbonic anhydrase XII (CA12) is the key carbonic anhydrase in epithelial fluid and HCO3 (-) secretion and works by activating the ductal Cl(-) -HCO3 (-) exchanger AE2. Delivery of CA12 to salivary glands increases salivation in mice and of the human mutation CA12(E143K) markedly inhibits it. The human mutation CA12(E143K) causes disease due to aberrant CA12 glycosylation, and misfolding resulting in loss of AE2 activity. Aberrant epithelial fluid and HCO3 (-) secretion is associated with many diseases. The activity of HCO3 (-) transporters depends of HCO3 (-) availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3 (-) supplier of ductal Cl(-) -HCO3 (-) exchanger AE2, but not of NBCe1-B. The E143K mutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

77 FR 71406 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric rate filings: Docket Numbers: ER10-2172-011; ER11-2016-006; ER10-2184-011; ER10- 2183-008; ER10-1048-008; ER10-2176-012; ER10-2192-011; ER11-2056-005...

Electronic state of Er in sputtered AlN:Er films determined by magnetic measurements

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

Narang, V.; Seehra, M. S., E-mail: mseehra@wvu.edu; Korakakis, D.

2014-12-07

The optoelectronic and piezoelectric properties of AlN:Er thin films have been of great recent interest for potential device applications. In this work, the focus is on the electronic state of Er in AlN:Er thin films prepared by reactive magnetron sputtering on (001) p-type Si substrate. X-ray diffraction shows that Er doping expands the lattice and the AlN:Er film has preferential c-plane orientation. To determine whether Er in AlN:Er is present as Er metal, Er{sub 2}O{sub 3}, or Er{sup 3+} substituting for Al{sup 3+}, detailed measurements and analysis of the temperature dependence (2 K–300 K) of the magnetization M at a fixed magneticmore » field H along with the M vs. H data at 2 K up to H = 90 kOe are presented. The presence of Er{sub 2}O{sub 3} and Er metal is ruled out since their characteristic magnetic transitions are not observed in the AlN:Er sample. Instead, the observed M vs. T and M vs. H variations are consistent with Er present as Er{sup 3+} substituting for Al{sup 3+} in AlN:Er at a concentration x = 1.08% in agreement with x = 0.94% ± 0.20% determined using x-ray photoelectron spectroscopy (XPS). The larger size of Er{sup 3+} vs. Al{sup 3+}explains the observed lattice expansion of AlN:Er.« less

Transcriptional repression of ER through hMAPK dependent histone deacetylation by class I HDACs.

PubMed

Plotkin, Amy; Volmar, Claude-Henry; Wahlestedt, Claes; Ayad, Nagi; El-Ashry, Dorraya

2014-09-01

Anti-estrogen therapies are not effective in ER- breast cancers, thus identifying mechanisms underlying lack of ER expression in ER- breast cancers is imperative. We have previously demonstrated that hyperactivation of MAPK (hMAPK) downstream of overexpressed EGFR or overexpression/amplification of Her2 represses ER protein and mRNA expression. Abrogation of hMAPK in ER- breast cancer cell lines and primary cultures causes re-expression of ER and restoration of anti-estrogen responses. This study was performed to identify mechanisms of hMAPK-induced transcriptional repression of ER. We found that ER promoter activity is significantly reduced in the presence of hMAPK signaling, yet did not identify specific promoter sequences responsible for this repression. We performed an epigenetic compound screen in an ER- breast cancer cell line that expresses hMAPK yet does not exhibit ER promoter hypermethylation. A number of HDAC inhibitors were identified and confirmed to modulate ER expression and estrogen signaling in multiple ER- cell lines and tumor samples lacking ER promoter methylation. siRNA-mediated knockdown of HDACs 1, 2, and 3 reversed the mRNA repression in multiple breast cancer cell lines and primary cultures and ER promoter-associated histone acetylation increased following MAPK inhibition. These data implicate histone deacetylation downstream of hMAPK in the observed ER mRNA repression associated with hMAPK. Importantly, histone deacetylation appears to be a common mechanism in the transcriptional repression of ER between ER- breast cancers with or without ER promoter hypermethylation.

Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.

PubMed

Fregno, Ilaria; Molinari, Maurizio

2018-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as "unfolded protein responses" that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40) and mammalian (FAM134B, SEC62, RTN3, and CCPG1) ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.

Kinetic stability analysis on electromagnetic filamentary structure

NASA Astrophysics Data System (ADS)

Lee, Wonjae; Krasheninnikov, Sergei

2014-10-01

A coherent radial transport of filamentary structures in SOL region is important for its characteristics that can increase unwanted high fluxes to plasma facing components. In the course of propagation in radial direction, the coherency of the filaments is significantly limited by electrostatic resistive drift instability (Angus et al., 2012). Considering higher plasma pressure, which would have more large impact in heat fluxes, electromagnetic effects will reduce the growth rate of the drift wave instability and increase the instabilities from electron inertial effects. According to a linear stability analysis on equations with fluid approximation, the maximum growth rate of the instability from the electron inertia is higher than that of drift-Alfvén wave instability in high beta filaments such as ELMs. However, the analysis on the high beta filaments requires kinetic approach, since the decreased collisionality will make the fluid approximation broken. Therefore, the kinetic analysis will be presented for the electromagnetic effects on the dynamics of filamentary structures. This work was supported by the USDOE Grants DE-FG02-04ER54739 and DE-SC0010413 at UCSD and also by the Kwanjeong Educational Foundation.

Shear-Flow Instability Saturation by Stable Modes: Hydrodynamics and Gyrokinetics

NASA Astrophysics Data System (ADS)

Fraser, Adrian; Pueschel, M. J.; Terry, P. W.; Zweibel, E. G.

2017-10-01

We present simulations of shear-driven instabilities, focusing on the impact of nonlinearly excited, large-scale, linearly stable modes on the nonlinear cascade, momentum transport, and secondary instabilities. Stable modes, which have previously been shown to significantly affect instability saturation [Fraser et al. PoP 2017], are investigated in a collisionless, gyrokinetic, periodic zonal flow using the Gene code by projecting the results of nonlinear simulations onto a basis of linear eigenmodes that includes both stable and unstable modes. Benchmarking growth rates against previous gyrokinetic studies and an equivalent fluid system demonstrates comparable linear dynamics in the fluid and gyrokinetic systems. Cases of driven and decaying shear-flow turbulence are compared in Gene by using a Krook operator as an effective forcing. For comparison with existing hydrodynamic and MHD shear-flow instability studies, we present results for the shear layer obtained by similar means with the code Dedalus. Supported by U.S. DOE Grant No. DE-FG02-89ER53291, the NSF, and UW-Madison.

Parallel Energy Transport in Detached DIII-D Divertor Plasmas

NASA Astrophysics Data System (ADS)

Leonard, A. W.; Lore, J. D.; Canik, J. M.; McLean, A. G.; Makowski, M. A.

2017-10-01

A comparison of experiment and modeling of detached divertor plasmas is examined in the context of parallel energy transport. Experimental estimates of power carried by electron thermal conduction versus plasma convection are experimentally inferred from power balance measurements of radiated power and target plate heat flux combined with Thomson scattering measurements of the Te profile along the divertor leg. Experimental profiles of Te exhibit relatively low gradients with Te < 15 eV from the X-point to the target implying transport dominated by convection. In contrast, fluid modeling with SOLPS produces sharp Te gradients for Te > 3 eV, characteristic of transport dominated by electron conduction through the bulk of the divertor. This discrepancy with experimental transport dominated by convection and modeling by conduction has significant implications for the radiative capacity of divertor plasmas and may explain at least part of the difficulty for fluid modeling to obtain the experimentally observed radiative losses. Comparisons are also made for helium plasmas where the match between experiment and modeling is much better. Work supported by the US DOE under DE-FC02-04ER54698.

20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

Characterization of aromatic residue-controlled protein retention in the endoplasmic reticulum of Saccharomyces cerevisiae.

PubMed

Mei, Meng; Zhai, Chao; Li, Xinzhi; Zhou, Yu; Peng, Wenfang; Ma, Lixin; Wang, Qinhong; Iverson, Brent L; Zhang, Guimin; Yi, Li

2017-12-15

An endoplasmic reticulum (ER) retention sequence (ERS) is a characteristic short sequence that mediates protein retention in the ER of eukaryotic cells. However, little is known about the detailed molecular mechanism involved in ERS-mediated protein ER retention. Using a new surface display-based fluorescence technique that effectively quantifies ERS-promoted protein ER retention within Saccharomyces cerevisiae cells, we performed comprehensive ERS analyses. We found that the length, type of amino acid residue, and additional residues at positions -5 and -6 of the C-terminal HDEL motif all determined the retention of ERS in the yeast ER. Moreover, the biochemical results guided by structure simulation revealed that aromatic residues (Phe-54, Trp-56, and other aromatic residues facing the ER lumen) in both the ERS (at positions -6 and -4) and its receptor, Erd2, jointly determined their interaction with each other. Our studies also revealed that this aromatic residue interaction might lead to the discriminative recognition of HDEL or KDEL as ERS in yeast or human cells, respectively. Our findings expand the understanding of ERS-mediated residence of proteins in the ER and may guide future research into protein folding, modification, and translocation affected by ER retention. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison of Er:YAG and Er:YSGG laser ablation of dental hard tissues

NASA Astrophysics Data System (ADS)

Stock, Karl; Hibst, Raimund; Keller, Ulrich

1997-12-01

To compare ablation quality of Er:YAG and Er:YSGG laser the surface quality, crater shape, mass loss, and temperature development were determined using the same fiber transmission system and handpiece. Similar crater depths for both lasers but greater diameters for the Er:YAG laser were measured. Also mass loss per pulse of the Er:YAG laser exceeds that of the Er:YSGG laser. Temperature development while ablation of dentin is more pronounced for the Er:YSGG laser. The observed minor ablation quality of the Er:YSGG laser can be explained by the lower absorption coefficient of dental hard substances compared to the Er:YAG laser.

Validation of a Computational Model for the SLS Core Stage Oxygen Tank Diffuser Concept and the Low Profile Diffuser - An Advanced Development Design for the SLS

NASA Technical Reports Server (NTRS)

Brodnick, Jacob; Richardson, Brian; Ramachandran, Narayanan

2015-01-01

The Low Profile Diffuser (LPD) project originated as an award from the Marshall Space Flight Center (MSFC) Advanced Development (ADO) office to the Main Propulsion Systems Branch (ER22). The task was created to develop and test an LPD concept that could produce comparable performance to a larger, traditionally designed, ullage gas diffuser while occupying a smaller volume envelope. Historically, ullage gas diffusers have been large, bulky devices that occupy a significant portion of the propellant tank, decreasing the tank volume available for propellant. Ullage pressurization of spacecraft propellant tanks is required to prevent boil-off of cryogenic propellants and to provide a positive pressure for propellant extraction. To achieve this, ullage gas diffusers must slow hot, high-pressure gas entering a propellant tank from supersonic speeds to only a few meters per second. Decreasing the incoming gas velocity is typically accomplished through expansion to larger areas within the diffuser which has traditionally led to large diffuser lengths. The Fluid Dynamics Branch (ER42) developed and applied advanced Computational Fluid Dynamics (CFD) analysis methods in order to mature the LPD design from and initial concept to an optimized test prototype and to provide extremely accurate pre-test predictions of diffuser performance. Additionally, the diffuser concept for the Core Stage of the Space Launch System (SLS) was analyzed in a short amount of time to guide test data collection efforts of the qualification of the device. CFD analysis of the SLS diffuser design provided new insights into the functioning of the device and was qualitatively validated against hot wire anemometry of the exterior flow field. Rigorous data analysis of the measurements was performed on static and dynamic pressure data, data from two microphones, accelerometers and hot wire anemometry with automated traverse. Feasibility of the LPD concept and validation of the computational model were demonstrated by the test data.

ER bodies in plants of the Brassicales order: biogenesis and association with innate immunity

PubMed Central

Nakano, Ryohei T.; Yamada, Kenji; Bednarek, Paweł; Nishimura, Mikio; Hara-Nishimura, Ikuko

2014-01-01

The endoplasmic reticulum (ER) forms highly organized network structures composed of tubules and cisternae. Many plant species develop additional ER-derived structures, most of which are specific for certain groups of species. In particular, a rod-shaped structure designated as the ER body is produced by plants of the Brassicales order, which includes Arabidopsis thaliana. Genetic analyses and characterization of A. thaliana mutants possessing a disorganized ER morphology or lacking ER bodies have provided insights into the highly organized mechanisms responsible for the formation of these unique ER structures. The accumulation of proteins specific for the ER body within the ER plays an important role in the formation of ER bodies. However, a mutant that exhibits morphological defects of both the ER and ER bodies has not been identified. This suggests that plants in the Brassicales order have evolved novel mechanisms for the development of this unique organelle, which are distinct from those used to maintain generic ER structures. In A. thaliana, ER bodies are ubiquitous in seedlings and roots, but rare in rosette leaves. Wounding of rosette leaves induces de novo formation of ER bodies, suggesting that these structures are associated with resistance against pathogens and/or herbivores. ER bodies accumulate a large amount of β-glucosidases, which can produce substances that potentially protect against invading pests. Biochemical studies have determined that the enzymatic activities of these β-glucosidases are enhanced during cell collapse. These results suggest that ER bodies are involved in plant immunity, although there is no direct evidence of this. In this review, we provide recent perspectives of ER and ER body formation in A. thaliana, and discuss clues for the functions of ER bodies. We highlight defense strategies against biotic stress that are unique for the Brassicales order, and discuss how ER structures could contribute to these strategies. PMID:24653729

Experiment-Model Comparisons of Turbulence, Transport, and Flows in a Magnetized Linear Plasma Using a Global Two-Fluid Braginskii Solver

NASA Astrophysics Data System (ADS)

Gilmore, M.; Fisher, D. M.; Kelly, R. F.; Hatch, M. W.; Rogers, B. N.

2017-10-01

Ongoing experiments and numerical modeling of the dynamics of electrostatic turbulence and transport in the presence of flow shear are being conducted in helicon plasmas in the linear HelCat (Helicon-Cathode) device. Modeling is being done using GBS, a 3D, global two-fluid Braginskii code that solves self-consistently for plasma equilibrium as well as fluctuations. Past experimental measurements of flows have been difficult to reconcile with simple expectations, such as azimuthal flows being dominated by Er x Bz rotation. Therefore, recent measurements have focused on understanding plasma flows, and the role of neutral dynamics. In the model, a set of two-fluid drift-reduced Braginskii equations are evolved using the Global Braginskii Solver Code (GBS). For low-field helicon-sourced Ar plasmas a non-negligible cross-field thermal collisional term must be added to shift the electric potential in the ion momentum and vorticity equations as the ions are unmagnetized. Significant radially and axially dependent neutral profiles are also included in the simulations to try and match those observed in HelCat. Ongoing simulations show a mode dependence on the axial magnetic field along with strong axial variations that suggest drift waves may be important in the low-field case. Supported by U.S. National Science Foundation Award 1500423.

Form follows function: the importance of endoplasmic reticulum shape.

PubMed

Westrate, L M; Lee, J E; Prinz, W A; Voeltz, G K

2015-01-01

The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.

Perturbative transport modeling and comparison to cold-pulse and heat-pulse propagation experiments in Alcator C-Mod and DIII-D

NASA Astrophysics Data System (ADS)

Rodriguez Fernandez, P.; White, A. E.; Cao, N. M.; Creely, A. J.; Greenwald, M. J.; Howard, N. T.; Hubbard, A. E.; Hughes, J. W.; Irby, J. H.; Petty, C. C.; Rice, J. E.; Alcator C-Mod Team

2016-10-01

Possible ``non-local'' transport phenomena are often observed in tokamak plasmas. Different models have been proposed to explain fast responses during perturbative transport experiments, including non-diffusive effects. Specific tools to characterize the dynamic behavior and power balance analysis using TRANSP and the quasi-linear trapped gyro-landau fluid code TGLF have been developed to analyze Alcator C-Mod experiments. Recent results from cold pulse experiments show that fast core temperature increases following edge cold-pulse injections (peak within 10ms , while τE 25ms) are not correlated with the direction of intrinsic rotation, and instead the amplitude of the core response depends on density, plasma current and RF input power. The propagation of the cold pulse can be compared with propagation of heat pulses from sawteeth, and both may be used to probe changes in temperature profile stiffness. A Laser Blow Off (LBO) system is being developed for DIII-D that will allow further validation and cross-machine comparison of cold pulse experiments. LBO at DIII-D will also allow for direct comparisons with ECH perturbative heat pulse experiments. Work supported by US DOE under Grants DE-FC02-99ER54512 (C-Mod) and DE-FC02-04ER54698 (DIII-D) and La Caixa Fellowship.

Improvement of Tenofovir vaginal release from hydrophilic matrices through drug granulation with hydrophobic polymers.

PubMed

Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Peña, Juan; Veiga, María-Dolores

2018-05-30

Sustained-release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) -an antiretroviral drug- sustained-release vaginal compacts combining two release control systems (by drug-loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X-ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV. Copyright © 2018 Elsevier B.V. All rights reserved.

Ricin A chain reaches the endoplasmic reticulum after endocytosis

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

Liu Qiong; Department of Biochemistry and Molecular Biology, Ningbo University Medical School, Ningbo 315211; Zhan Jinbiao

Ricin is a potent ribosome inactivating protein and now has been widely used for synthesis of immunotoxins. To target ribosome in the mammalian cytosol, ricin must firstly retrograde transport from the endomembrane system to reach the endoplasmic reticulum (ER) where the ricin A chain (RTA) is recognized by ER components that facilitate its membrane translocation to the cytosol. In the study, the fusion gene of enhanced green fluorescent protein (EGFP)-RTA was expressed with the pET-28a (+) system in Escherichia coli under the control of a T7 promoter. The fusion protein showed a green fluorescence. The recombinant protein can be purifiedmore » by metal chelated affinity chromatography on a column of NTA. The rabbit anti-GFP antibody can recognize the fusion protein of EGFP-RTA just like the EGFP protein. The cytotoxicity of EGFP-RTA and RTA was evaluated by the MTT assay in HeLa and HEP-G2 cells following fluid-phase endocytosis. The fusion protein had a similar cytotoxicity of RTA. After endocytosis, the subcellular location of the fusion protein can be observed with the laser scanning confocal microscopy and the immuno-gold labeling Electro Microscopy. This study provided important evidence by a visualized way to prove that RTA does reach the endoplasmic reticulum.« less

Magnetocaloric properties of rare-earth substituted DyCrO{sub 3}

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

McDannald, A.; Jain, M., E-mail: menka.jain@uconn.edu; Department of Physics, University of Connecticut, Storrs, Connecticut 06269

Recently, there has been a focus on the need for efficient refrigeration technology without the use of expensive or harmful working fluids, especially at temperatures below 30 K. Solid state refrigeration, based on the magnetocaloric effect, provides a possible solution to this problem. The rare-earth chromites (RCrO{sub 3}), especially DyCrO{sub 3}, with its large magnetic moment dysprosium ion, are potential candidates for such an application. The Dy{sup 3+} ordering transition at low temperatures (<10 K) likely causes a large magnetocaloric response in this material. This study investigates the possibility of tuning the magnetocaloric properties through the use of rare-earth substitution. Both Y{supmore » 3+} and Ho{sup 3+} substitutions were found to decrease the magnetocaloric response by disrupting the R{sup 3+} ordering. Whereas Er{sup 3+} substitution was found to increase the magnetocaloric response, likely due to an increase in the R{sup 3+} ordering temperature. The large magnetocaloric entropy change of Er{sup 3+} substituted DyCrO{sub 3} (10.92 J/kg K with a relative cooling power of 237 J/kg at 40 kOe and 5 K) indicates that this material system is well suited for low temperature (<30 K) solid state refrigeration applications.« less

Instantaneous ballistic velocity of suspended Brownian nanocrystals measured by upconversion nanothermometry

NASA Astrophysics Data System (ADS)

Brites, Carlos D. S.; Xie, Xiaoji; Debasu, Mengistie L.; Qin, Xian; Chen, Runfeng; Huang, Wei; Rocha, João; Liu, Xiaogang; Carlos, Luís D.

2016-10-01

Brownian motion is one of the most fascinating phenomena in nature. Its conceptual implications have a profound impact in almost every field of science and even economics, from dissipative processes in thermodynamic systems, gene therapy in biomedical research, artificial motors and galaxy formation to the behaviour of stock prices. However, despite extensive experimental investigations, the basic microscopic knowledge of prototypical systems such as colloidal particles in a fluid is still far from being complete. This is particularly the case for the measurement of the particles' instantaneous velocities, elusive due to the rapid random movements on extremely short timescales. Here, we report the measurement of the instantaneous ballistic velocity of Brownian nanocrystals suspended in both aqueous and organic solvents. To achieve this, we develop a technique based on upconversion nanothermometry. We find that the population of excited electronic states in NaYF4:Yb/Er nanocrystals at thermal equilibrium can be used for temperature mapping of the nanofluid with great thermal sensitivity (1.15% K-1 at 296 K) and a high spatial resolution (<1 μm). A distinct correlation between the heat flux in the nanofluid and the temporal evolution of Er3+ emission allows us to measure the instantaneous velocity of nanocrystals with different sizes and shapes.

78 FR 50408 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric rate filings: Docket Numbers: ER10-1246-003; ER10-1982-004; ER10-1253-003; ER10- 1252-003; ER13-764-002; ER12-2498-003; ER12-2499-003. Applicants: Consolidated Edison Energy, Inc., Consolidated...

Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status

PubMed Central

Li, Qiyuan; Eklund, Aron C.; Juul, Nicolai; Haibe-Kains, Benjamin; Workman, Christopher T.; Richardson, Andrea L.; Szallasi, Zoltan; Swanton, Charles

2010-01-01

Background Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold[1], [2]. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome. Methodology/Principal Findings Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHC-based ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that between 15.1% and 21.8% patients of IHC-based negative ER status would be classified with ER positive breast cancer. Conclusion/Significance Expression-based ER status classification may complement IHC to minimise false negative ER status classification and optimise patient stratification for endocrine therapies. PMID:21152022

Development of Polythiophene/Acrylonitrile-Butadiene Rubbers for Artificial Muscle

NASA Astrophysics Data System (ADS)

Thipdech, Pacharavalee; Sirivat, Anuvat

2007-03-01

Electroactive polymers (EAPs) can respond to the applied electrical field by an extension or a retraction. In this work, we are interested in using an elastomeric blend for electroactive applications, acrylonitirle-butadiene rubber (NBR) containing a conductive polymer (Poly(3-thiopheneacetic acid, PTAA); the latter can be synthesized via oxidative polymerization. FT-IR, Thermogravimetric analysis (TGA), ^1H-NMR, UV-visible spectroscopy, and SEM are used to characterize the conductive polymer. Electrorheological properties are measured and investigated in terms of acrylonitrile content, blending ratio, doping level, and temperature. Experiments are carried out under oscillatory shear mode and with applied electric field strength varying from 0 to 2 kV/mm. Dielectric properties, conductivities are measured and correlated with the storage modulus responses. The storage modulus sensitivity, δG'G'0of the pure rubbers increases with increasing electric field strength. They attain the maximum values of about 30% and become constant at electric strength at and above 1000 V/mm.

Electrokinetic Particle Aggregation and Flow Instabilities in Non-Dilute Colloidal Suspensions

NASA Astrophysics Data System (ADS)

Navaneetham, Guru; Posner, Jonathan

2007-11-01

An experimental investigation of electrokinetic particle aggregation and flow instabilities of non-dilute colloidal suspensions in microfabricated channels is presented. The addition of charged colloidal particles can alter the solution's conductivity, permittivity as well as the average particle electrophoretic mobility. In this work, a colloid volume fraction gradient is achieved at the intersection of a Y-shaped PDMS microchannel. The solution conductivity and the particle mobility as a function of the particle (500 nm polystyrene) volume fraction are presented. The critical conditions required for particle aggregation and flow instability are given along with a scaling analysis which shows that the flow becomes unstable at a critical electric Rayleigh number for a wide range of applied electric fields and colloid volume fractions. Electrokinetic particle aggregation and instabilities of non-dilute colloidal suspensions may be important for applications such as the electrophoretic deposition of particles to form micropatterned colloidal assemblies, electrorheological devices, and on-chip, electrokinetic manipulation of colloids.

Electrically modulated capillary filling imbibition of nematic liquid crystals

NASA Astrophysics Data System (ADS)

Dhar, Jayabrata; Chakraborty, Suman

2018-04-01

The flow of nematic liquid crystals (NLCs) in the presence of an electric field is typically characterized by the variation in its rheological properties due to transition in its molecular arrangements. Here, we bring out a nontrivial interplay of a consequent alteration in the resistive viscous effects and driving electrocapillary interactions, toward maneuvering the capillary filling dynamics over miniaturized scales. Considering a dynamic interplay of the relevant bulk and interfacial forces acting in tandem, our results converge nicely to previously reported experimental data. Finally, we attempt a scaling analysis to bring forth further insight to the reported observations. Our analysis paves the way for the development of microfluidic strategies with previously unexplored paradigms of interaction between electrical and fluidic phenomenon, providing with an augmented controllability on capillary filling as compared to tthose reported to be achievable by the existing strategies. This, in turn, holds utilitarian scopes in improved designs of functional capillarities in electro-optical systems, electrorheological utilities, electrokinetic flow control, as well as in interfacing and imaging systems for biomedical microdevices.

Thermodynamic and dynamic behaviors of self-organizing polymeric systems

NASA Astrophysics Data System (ADS)

Zhao, Yiqiang

Two topics of self-organizing polymeric systems are explored in this work: thermodynamic and dynamic properties of liquid crystal polymers in solutions and rheological behaviors of self-organizing gels. For dilute nematic solutions of end-on side-chain liquid crystal polysiloxanes (SCLCP) dissolved in 5CB, the chain anisotropies R∥/R ⊥, obtained from electrorheological(ER) analysis based on the Brochard model, are consistent with independent measurements of Rg∥/R g⊥ via small-angle neutron scattering (SANS), which unambiguously demonstrating a slightly prolate SCLCP chain conformation. Dissolution of this prolate SCLCP in flow-aligning 5CB produces a tumbling flow, clearly indicating a discrepancy with the Brochard hydrodynamic theory which predicts such a transition only for oblate conformation. A numerical comparison using a modified version of the Brochard model leads to improved self-consistent agreement between SANS, ER and shear transient experiments. The molecular weight dependence of the chain conformational relaxation time it indicates an extended SCLCP chain conformation in 5CB. SANS analysis suggests that the SCLCP conformation is sensitive to the solvent interaction, i.e. a more extended conformation is observed in isotropic acetone-d6 than in nematic 5CB. A SANS conformational study of SCLCCs with methoxyphenylbenzoate mesogenic side group in CDC13 demonstrates that the form factor of a single comb-like SCLCP chain is well described by a wormlike chain model with finite cross-sectional thickness over the entire q range, taking into account the molecular weight polydispersity. Consistent with measurement of a large R g from low q analysis, the resulting persistence length lp is in the range 28˜32 A, substantially larger than that of unsubstituted polydimethylsiloxane (PDMS) chain (l p =5.8 A), which suggests a relatively rigid SCLCP chain due to the influence of densely attached mesogenic groups. For nematic mixtures of copolysiloxane SCLCP in 5OCB, a metastably extended miscible nematic range is observed at low SCLCP concentration upon cooling. Onset of an induced smectic phase occurs upon cooling at 60%wt SCLCP concentration which corresponds to 48:52 molar ratio of mesogens. Dielectric spectra of these mixtures over a wide concentration range exhibit two distinct regimes of relaxation behavior reflecting the crossover from dilute and semidilute to concentrated regime. Rheological behavior of a metallo-supramolecular gel with thixotropic feature is explored to understand the viscoelastic behaviors of self-assembling networks consisting of "living polymers". A well-defined yield point and non-linear viscoelasticity at small strain are probed via the controlled-stress and controlled-strain measurements, respectively. The self-assembled network is readily presheared into a Newtonian sol and displays a three-stage kinetic recovery process, closely associated with the metal ion-ligand binding kinetics and related phase behaviors. Finally, we investigate the viscoelastic properties of a novel colloidal gel in which macrocycles self-assemble into interconnected self-organized clusters. A series of rheological experiments are combined to reveal the shear responsive nature as well as linear and nonlinear viscoelasticity of this gel. Certain features of observed viscoelastic properties demonstrate the characteristics of the behavior of colloidal gels which show slow glassy dynamics. The negative temperature dependence of the storage modulus at low frequency suggests that enthalpic contributions to elasticity need to be considered, presumably due to internal energy changes upon deformation.

Etude des interdiffusions en phase solide dans le contact Er/GaAs

NASA Astrophysics Data System (ADS)

Députier, S.; Guivarc'h, A.; Caulet, J.; Minier, M.; Guérin, R.

1994-05-01

Solid state interdiffusions between a thin film of erbium deposited under vacuum conditions and (001) and (111) GaAs substrates were investigated in the temperature range 350-800 ^{circ}C. Complementary analysis methods (RBS, X-ray diffraction) allow us to point out, according to annealing temperatures, successives steps of the interaction corresponding to different mixtures of phases, essentially binaries. These steps are strongly depending on the GaAs substrate orientation, especially the final step of the interdiffusions. On (001) GaAs, only two steps have been observed : no visible interaction is noticed between erbium and GaAs before 600 ^{circ}C ; the interaction begins at 600 ^{circ}C, evolves slightly and leads at 800 ^{circ}C to the nominal composition " Er{10}GaAs " which corresponds to a mixture of several phases Er5Ga3, Er and ErAs. On (111) GaAs, several steps of interaction have been found ; first of all, erbium reacts with the substrate at 400 ^{circ}C (Er5Ga3 + Er mixture), then the reaction is continuing at 600 ^{circ}C (Er5Ga3 + Er + ErAs mixture) before reaching at 800 ^{circ}C the nominal composition " Er{1,5}GaAs ", which is in fact a mixture of the three binaries ErAs + ErGa2 + Er3Ga5. It can be noticed that the 800 ^{circ}C annealing is not sufficient to reach the mixture of the phases ErAs + Ga which, according to the ternary phase diagram, should be the final stage of the interaction Er/GaAs. The analysis of the Er/GaAs interdiffusions shows that ErAs is the " key " compound around which the interaction progresses. This compound appears as an ideal candidate to realize epitaxial ErAs/GaAs heterostructures. Les interdiffusions en phase solide entre une couche mince d'erbium déposée dans des conditions d'ultra-vide et des substrats de GaAs orientés (001) et (111) ont été étudiées après des traitements thermiques d'une heure entre 350 et 800 ^{circ}C. L'utilisation de techniques complémentaires d'analyse (RBS, diffraction X) a permis de mettre en évidence, en fonction de la température de recuit, plusieurs étapes successives d'interaction correspondant à des mélanges de phases, essentiellement des binaires. Elles dépendent fortement de l'orientation du substrat de GaAs, en particulier l'étape finale des interactions. Sur GaAs (001), seules deux étapes ont été observées : avant 600 ^{circ}C, il n'y a pas d'interaction visible de l'erbium avec le substrat ; celle-ci ne s'amorce qu'à 600 ^{circ}C pour n'évoluer ensuite que faiblement et conduire, à 800 ^{circ}C, à une composition nominale " Er{10}GaAs ", mélange des phases Er5Ga3 + Er + ErAs. Sur GaAs (111), plusieurs étapes d'interaction sont observées : l'erbium réagit avec le substrat dès 400 ^{circ}C (mélange des phases Er5Ga3 + Er), puis l'interaction se poursuit à 600 ^{circ}C (mélange Er5Ga3 + Er + ErAs) avant d'atteindre à 800 ^{circ}C la composition nominale " Er{1,5}GaAs ", constituée d'un mélange de grains des trois binaires ErAs + ErGa2 + Er3Ga5. Il faut noter que le recuit à 800 ^{circ}C n'est pas suffisant pour atteindre le mélange de phases Ga + ErAs qui, selon le diagramme ternaire, devrait être le stade ultime de l'interaction Er/GaAs. L'analyse des interdiffusions Er/GaAs montre que ErAs est le composé " clé " autour duquel pivote l'interaction Er/GaAs. Ce composé apparaît comme un candidat idéal pour la réalisation d'hétérostructures épitaxiées ErAs/GaAs.

Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.

PubMed

Kim, Jinhwan; Choi, Tae Gyu; Ding, Yan; Kim, Yeonghwan; Ha, Kwon Soo; Lee, Kyung Ho; Kang, Insug; Ha, Joohun; Kaufman, Randal J; Lee, Jinhwa; Choe, Wonchae; Kim, Sung Soo

2008-11-01

Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.

20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Adjustments to the widow(er)'s, disabled widow..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Adjustments to the widow(er)'s, disabled widow..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

78 FR 67355 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

...-1939-006; ER11-2754-006; ER12- 999-004; ER12-1002-004; ER12-1005-004; ER12-1006-004; ER12-1007-005.... Filed Date: 10/31/13. Accession Number: 20131031-5189. Comments Due: 5 p.m. ET 11/21/13. Docket Numbers... States Power Company, a Minnesota corporation submits 2013-10-31--SuppTheRecordInER14-23 to be effective...

Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations.

PubMed

Zhang, Xiaomei; Podsypanina, Katrina; Huang, Shixia; Mohsin, Syed K; Chamness, Gary C; Hatsell, Sarah; Cowin, Pam; Schiff, Rachel; Li, Yi

2005-06-16

The majority (75%) of human breast cancers express estrogen receptor (ER). Although ER-positive tumors usually respond to antiestrogen therapies, 30% of them do not. It is not known what controls the ER status of breast cancers or their responsiveness to antihormone interventions. In this report, we document that transgenic (TG) expression of Wnt-1 in mice induces ER-positive tumors. Loss of Pten or gain of Ras mutations during the evolution of tumors in Wnt-1 TG mice has no effect on the expression of ER, but overexpression of Neu or loss of p53 leads to ER-negative tumors. Thus, our results provide compelling evidence that expression of ER in breast cancer may be influenced by specific genetic changes that promote cancer progression. These findings constitute a first step to explore the molecular mechanisms leading to ER-positive or ER-negative mammary tumors. In addition, we find that ER-positive tumors arising in Wnt-1 TG mice are refractory to both ovariectomy and the ER antagonist tamoxifen, but lose ER expression with tamoxifen, suggesting that antiestrogen selects for ER-negative tumor cells and that the ER-positive cell fraction is dispensable for growth of these tumors. This is a first report of a mouse model of antiestrogen-resistant ER-positive breast cancers, and could provide a powerful tool to study the molecular mechanisms that control antiestrogen resistance.

Additive treatment improves survival in elderly patients after non-curative endoscopic resection for early gastric cancer.

PubMed

Jung, Da Hyun; Lee, Yong Chan; Kim, Jie-Hyun; Lee, Sang Kil; Shin, Sung Kwan; Park, Jun Chul; Chung, Hyunsoo; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin

2017-03-01

Endoscopic resection (ER) is accepted as a curative treatment option for selected cases of early gastric cancer (EGC). Although additional surgery is often recommended for patients who have undergone non-curative ER, clinicians are cautious when managing elderly patients with GC because of comorbid conditions. The aim of the study was to investigate clinical outcomes in elderly patients following non-curative ER with and without additive treatment. Subjects included 365 patients (>75 years old) who were diagnosed with EGC and underwent ER between 2007 and 2015. Clinical outcomes of three patient groups [curative ER (n = 246), non-curative ER with additive treatment (n = 37), non-curative ER without additive treatment (n = 82)] were compared. Among the patients who underwent non-curative ER with additive treatment, 28 received surgery, three received a repeat ER, and six experienced argon plasma coagulation. Patients who underwent non-curative ER alone were significantly older than those who underwent additive treatment. Overall 5-year survival rates in the curative ER, non-curative ER with treatment, and non-curative ER without treatment groups were 84, 86, and 69 %, respectively. No significant difference in overall survival was found between patients in the curative ER and non-curative ER with additive treatment groups. The non-curative ER groups were categorized by lymph node metastasis risk factors to create a high-risk group that exhibited positive lymphovascular invasion or deep submucosal invasion greater than SM2 and a low-risk group without risk factors. Overall 5-year survival rate was lowest (60 %) in the high-risk group with non-curative ER and no additive treatment. Elderly patients who underwent non-curative ER with additive treatment showed better survival outcome than those without treatment. Therefore, especially with LVI or deep submucosal invasion, additive treatment is recommended in patients undergoing non-curative ER, even if they are older than 75 years.

ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

PubMed

Rahmati, Marveh; Moosavi, Mohammad Amin; McDermott, Michael F

2018-04-22

Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physical Chemical and in-situ CTD (Conductivity/Temperature/Depth) Data from the Ajax Expedition in the South Atlantic Ocean.

DTIC Science & Technology

1985-12-15

SALINITY SIGMA SIGMA S1; KA OVA DYN M T OXYGEN 000 I10 P04 Nn lA? 02 09 A EG C ’Er, C TAETA 2 4 MIL PCI UP/IL U MIL UIL 04/L . 15L 2,641 .641 03.923...epart ment i if the Nays t S TOI KA Priest fi 1ce N,,’.,l OLcin Sysrenis Center Prof C’ G 11 Rititf N) 0 ?% R /( %R San Iliego. C A 921 i2 I nisersity if...Dr. Adriana Huyer Cambridge, MA 02139 U.S. Dept. of Commerce, NOAA School of Oceanography Geophysical Fluid Dynamics Lab Oregon State University Dr

Adenocarcinoma of urinary bladder: A report of two patients.

PubMed

Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

Expression of estrogen receptors-alpha and -beta in the pregnant ovine uterine artery endothelial cells in vivo and in vitro.

PubMed

Liao, Wu Xiang; Magness, Ronald R; Chen, Dong-Bao

2005-03-01

Estrogen is recognized to be one of the driving forces in increases in uterine blood flow through both rapid and delayed actions via binding to its receptors, ER alpha and ER beta at the uterine artery (UA) wall, and especially in UA endothelium (UAE). However, information regarding estrogen receptor (ER) expression in UAE is limited. This study was designed to test whether ERs are expressed in UAE in vivo, and if they are, whether these receptors are maintained in cultured UA endothelial cells (UAECs) in vitro. By using immunohistochemical and Western blot analyses, we clearly demonstrated ER alpha and ER beta protein expression in pregnant (Days 120-130) sheep UA and UAE in vivo and as well as cultured UAECs in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) amplified both ER alpha and ER beta mRNAs in UA, UAE, and UAECs. Of interest, a truncated ER beta (ER beta2) variant due to a splicing deletion of exon 5 of the ER beta gene was detected in these cells. Quantitative RT-PCR analysis revealed that ER alpha mRNA levels are approximately 8-fold (P < 0.01) higher than that of ER beta in UAECs, indicating that ER alpha may play a more important role than ER beta in the UAEC responses to estrogen. Fluorescence immunolabeling analysis showed that ER alpha is present in both nuclei and plasma membranes in UAECs, and the latter is also colocalized with caveolin-1. The membrane and nuclear ER alpha presumably participate in rapid and delayed responses, respectively, to estrogen on UAE. Taken together, our data demonstrated that UAE is a direct target of estrogen actions and that the UAEC culture model we established is suitable for dissecting estrogen actions on UAE.

Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo

PubMed Central

Colla, Emanuela; Coune, Philippe; Liu, Ying; Pletnikova, Olga; Troncoso, Juan C; Iwatsubo, Takeshi; Schneider, Bernard L.; Lee, Michael K.

2012-01-01

Accumulation of misfolded α-synuclein (αS) is mechanistically linked to neurodegeneration in Parkinson's disease (PD) and other α-synucleinopathies. However, how αS causes neurodegeneration is unresolved. Because cellular accumulation of misfolded proteins can lead to endoplasmic reticulum stress/unfolded protein response (ERS/UPR), chronic ERS could contribute to neurodegeneration in α-synucleinopathy. Using the A53T mutant human αS transgenic (A53TαS Tg) mouse model of α-synucleinopathy, we show that disease onset in the αS Tg model is coincident with induction of ER chaperone in neurons exhibiting αS pathology. However, the neuronal ER chaperone induction was not accompanied by the activation of phospho-eIF2α, indicating that α-synucleinopathy is associated with abnormal UPR that could promote cell death. Induction of ERS/UPR was associated with increased levels of ER/microsomal (ER/M) associated αS monomers and aggregates. Significantly, human PD cases also exhibit higher relative levels of ER/M αS than the control cases. Moreover, αS interacts with ER chaperones and overexpression of αS sensitizes neuronal cells to ERS-induced toxicity, suggesting that αS may have direct impact on ER function. This view is supported by the presence of ERS-activated caspase-12 and the accumulation of ER-associated polyubiquitin. More important, treatment with Salubrinal, an anti-ERS compound, significantly attenuates disease manifestations in both the A53TαS Tg mouse model and the Adeno-associated Virus-transduced rat model of A53T α S-dependent dopaminergic neurodegeneration. Our data indicate that the accumulation αS within ER leads to chronic ER stress conditions that contribute to neurodegeneration in α-synucleinopathies. Attenuating chronic ERS could be an effective therapy for PD and other α-synucleinopathies. PMID:22399753

Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress.

PubMed

Shaheen, Alaa

2018-05-05

The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

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

Leanos-Castaneda, Olga; Kraak, Glen van der

2007-10-15

The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbowmore » trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ER{beta}, implying, furthermore that compounds which only exhibit ER{alpha} selectivity are not detected by vitellogenin bioassay.« less

ErbB2 Trafficking and Signaling in Human Vestibular Schwannomas

DTIC Science & Technology

2008-10-01

E -Mail...R ho G D I A. B. C. D. E . ER K /R ho G D I ER K /R ho G D I pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER...c on tr ol ) 0 20 40 60 80 100 Control I-JIP 30 μM I-JIP 100 μM SP60025 20 μM B rd U- po si tiv e V S ce lls (% c on tr ol ) B rd U- po si tiv e

ERdj5 sensitizes neuroblastoma cells to endoplasmic reticulum stress-induced apoptosis.

PubMed

Thomas, Christophoros G; Spyrou, Giannis

2009-03-06

Down-regulation of the unfolded protein response (UPR) can be therapeutically valuable in cancer treatment, and endoplasmic reticulum (ER)-resident chaperone proteins may thus be targets for developing novel chemotherapeutic strategies. ERdj5 is a novel ER chaperone that regulates the ER-associated degradation of misfolded proteins through its associations with EDEM and the ER stress sensor BiP. To investigate whether ERdj5 can regulate ER stress signaling pathways, we exposed neuroblastoma cells overexpressing ERdj5 to ER stress inducers. ERdj5 promoted apoptosis in tunicamycin, thapsigargin, and bortezomib-treated cells. To provide further evidence that ERdj5 induces ER stress-regulated apoptosis, we targeted Bcl-2 to ER of ERdj5-overexpressing cells. Targeting the Bcl-2 to ER prevented the apoptosis induced by ER stress inducers but not by non-ER stress apoptotic stimuli, suggesting induction of ER stress-regulated apoptosis by ERdj5. ERdj5 enhanced apoptosis by abolishing the ER stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) and the subsequent translational repression. ERdj5 was found to inhibit the eIF2alpha phosphorylation under ER stress through inactivating the pancreatic endoplasmic reticulum kinase. The compromised integrated stress response observed in ERdj5-overexpressing ER-stressed cells due to repressed eIF2alpha phosphorylation correlated with impaired neuroblastoma cell resistance under ER stress. These results demonstrate that ERdj5 decreases neuroblastoma cell survival by down-regulating the UPR, raising the possibility that this protein could be a target for anti-tumor approaches.

16 CFR Appendix L to Part 305 - Sample Labels

Code of Federal Regulations, 2010 CFR

2010-01-01

... Part 305—Sample Labels ER29AU07.122 PROTOTYPE LABEL 1 ER29AU07.123 PROTOTYPE LABEL 2 ER29AU07.124 PROTOTYPE LABEL 3 ER29AU07.125 PROTOTYPE LABEL 4 ER29AU07.126 SAMPLE LABEL 1 ER29AU07.127 SAMPLE LABEL 2...

77 FR 66829 - Notice of Compliance Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [ Docket Nos. ER13-187-000; ER13-187-001, et al.] Notice of Compliance Filings Docket Nos. Midwest Independent Transmission System ER13-187-000 Docket No. ER13- Operator, Inc. 187-001. ISO New England Inc ER13-193-000. PJM Transmission Owners ER13...

Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress

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

Kanemoto, Soshi; Nitani, Ryota; Murakami, Tatsuhiko

The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK). Furthermore, exosome release was also increased during ER stress. However, in IRE1 ormore » PERK deficient cells, exosome release was not upregulated, indicating that IRE1- and PERK-mediated pathways are involved in ER stress-dependent exosome release. - Highlights: • Endoplasmic reticulum (ER) stress induces multivesicular body (MVB) formation. • ER stress transducers IRE1 and PERK mediate MVB formation. • Exosome release is enhanced after ER stress. • IRE1 or PERK deficiency blocks upregulation of ER stress-dependent exosome release.« less

Regulation of endoplasmic reticulum turnover by selective autophagy.

PubMed

Khaminets, Aliaksandr; Heinrich, Theresa; Mari, Muriel; Grumati, Paolo; Huebner, Antje K; Akutsu, Masato; Liebmann, Lutz; Stolz, Alexandra; Nietzsche, Sandor; Koch, Nicole; Mauthe, Mario; Katona, Istvan; Qualmann, Britta; Weis, Joachim; Reggiori, Fulvio; Kurth, Ingo; Hübner, Christian A; Dikic, Ivan

2015-06-18

The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.

Smart portable rehabilitation devices.

PubMed

Mavroidis, Constantinos; Nikitczuk, Jason; Weinberg, Brian; Danaher, Gil; Jensen, Katherine; Pelletier, Philip; Prugnarola, Jennifer; Stuart, Ryan; Arango, Roberto; Leahey, Matt; Pavone, Robert; Provo, Andrew; Yasevac, Dan

2005-07-12

The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s). In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device. Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit. Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved.

Smart portable rehabilitation devices

PubMed Central

Mavroidis, Constantinos; Nikitczuk, Jason; Weinberg, Brian; Danaher, Gil; Jensen, Katherine; Pelletier, Philip; Prugnarola, Jennifer; Stuart, Ryan; Arango, Roberto; Leahey, Matt; Pavone, Robert; Provo, Andrew; Yasevac, Dan

2005-01-01

Background The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s). Methods In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device. Results Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit. Conclusion Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved. PMID:16011801

Growth, spectroscopic properties and laser output of Er : Ca 4YO(BO 3) 3 and Er : Yb : Ca 4YO(BO 3) 3 crystals

NASA Astrophysics Data System (ADS)

Zhang, Huaijin; Meng, Xianlin; Wang, Changqing; Wang, Pu; Zhu, Li; Liu, Xuesong; Dong, Chunming; Yang, Yuyong; Cheng, Ruiping; Dawes, Judith; Piper, Jim; Zhang, Shaojun; Sun, Lianke

2000-09-01

In this paper, Er : Ca 4YO(BO 3) 3 (Er : YCOB) and Er : Yb : Ca 4YO(BO 3) 3 (Er : Yb : YCOB) crystals with large size and excellent quality have been grown by the Czochralski method. The absorption and emission spectra of Er : YCOB and Er : Yb : YCOB crystals have been measured; the emission spectrum of Er : Yb : YCOB crystal shows that the strongest emission peak is located at 1537 nm. An output power of about 2 mW at the wavelength of 1553 nm has been obtained under the pumping power of a fiber-coupled laser diode (LD) of 1600 mW at 976 nm, using a Y direction cut 2.5 mm thick Er : Yb : YCOB crystal sample.

ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB

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

Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi

Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-L{alpha}, an upstream signaling molecule of ER stress, decreased at 1-4 h after 10more » mJ/cm{sup 2} irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm{sup 2} UVB at 4 h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.« less

Cloning, in Vitro expression, and novel phylogenetic classification of a channel catfish estrogen receptor

USGS Publications Warehouse

Xia, Z.; Patino, R.; Gale, W.L.; Maule, A.G.; Densmore, L.D.

1999-01-01

We obtained two channel catfish estrogen receptor (ccER) cDNA from liver of female fish using RT–PCR. The two fragments were identical in sequence except that the smaller one had an out-of-frame deletion in the E domain, suggesting the existence of ccER splice variants. The larger fragment was used to screen a cDNA library from liver of a prepubescent female. A cDNA was obtained that encoded a 581-amino-acid ER with a deduced molecular weight of 63.8 kDa. Extracts of COS-7 cells transfected with ccER cDNA bound estrogen with high affinity (Kd = 4.7 nM) and specificity. Maximum parsimony and Neighbor Joining analyses were used to generate a phylogenetic classification of ccER on the basis of 18 full-length ER sequences. The tree suggested the existence of two major ER branches. One branch contained two clearly divergent clades which included all piscine ER (except Japanese eel ER) and all tetrapod ERα, respectively. The second major branch contained the eel ER and the mammalian ERβ. The high degree of divergence between the eel ER and mammalian ERβ suggested that they also represent distinct piscine and tetrapod ER. These data suggest that ERα and ERβ are present throughout vertebrates and that these two major ER types evolved by duplication of an ancestral ER gene. Sequence alignments with other members of the nuclear hormone receptor superfamily indicated the presence of 8 amino acids in the E domain that align exclusively among ER. Four of these amino acids have not received prior research attention and their function is unknown. The novel finding of putative ER splice variants in a nonmammalian vertebrate and the novel phylogenetic classification of ER offer new perspectives in understanding the diversification and function of ER.

Integration of ERS and ASAR Time Series for Differential Interferometric SAR Analysis

NASA Astrophysics Data System (ADS)

Werner, C. L.; Wegmüller, U.; Strozzi, T.; Wiesmann, A.

2005-12-01

Time series SAR interferometric analysis requires SAR data with good temporal sampling covering the time period of interest. The ERS satellites operated by ESA have acquired a large global archive of C-Band SAR data since 1991. The ASAR C-Band instrument aboard the ENVISAT platform launched in 2002 operates in the same orbit as ERS-1 and ERS-2 and has largely replaced the remaining operational ERS-2 satellite. However, interferometry between data acquired by ERS and ASAR is complicated by a 31 MHz offset in the radar center frequency between the instruments leading to decorrelation over distributed targets. Only in rare instances, when the baseline exceeds 1 km, can the spectral shift compensate for the difference in the frequencies of the SAR instruments to produce visible fringes. Conversely, point targets do not decorrelate due to the frequency offset making it possible to incorporate the ERS-ASAR phase information and obtain improved temporal coverage. We present an algorithm for interferometric point target analysis that integrates ERS-ERS, ASAR-ASAR and ERS-ASAR data. Initial analysis using the ERS-ERS data is used to identify the phase stable point-like scatterers within the scene. Height corrections relative to the initial DEM are derived by regression of the residual interferometric phases with respect to perpendicular baseline for a set of ERS-ERS interferograms. The ASAR images are coregistered with the ERS scenes and the point phase values are extracted. The different system pixel spacing values between ERS and ASAR requires additional refinement in the offset estimation and resampling procedure. Calculation of the ERS-ASAR simulated phase used to derive the differential interferometric phase must take into account the slightly different carrrier frequencies. Differential ERS-ASAR point phases contain an additional phase component related to the scatterer location within the resolution element. This additional phase varies over several cycles making the differential interferogram appear as uniform phase noise. We present how this point phase difference can be determined and used to correct the ERS-ASAR interferograms. Further processing proceeds as with standard ERS-ERS interferogram stacks utilizing the unwrapped point phases to obtain estimates of the deformation history, and path delay due to variations in tropospheric water vapor. We show and discuss examples demonstrating the success of this approach.

ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

PubMed

Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

2012-12-11

Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

78 FR 57375 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

... Customer Matters, Reliability, Security and Market Operations. A-3 AD12-12-000 Coordination Between Natural Gas and Electricity Markets. Electric E-1 ER12-1179-003 Southwest Power Pool, Inc. ER12-1179-004 ER12... E-11 ER13-2031-000 Southwest Power Pool, Inc. ER13-2033-000 E-12 ER12-2292-001 Southwest Power Pool...

78 FR 34368 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric rate filings: Docket Numbers: ER10-2238-005; ER10-2239-005; ER10-2237-004; ER10- 1821-006; ER11-4475-006; ER12-896-001. Applicants: Indigo Generation LLC, Larkspur Energy LLC, Wildflower Energy LP...

Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses' Health Study.

PubMed

Marotti, Jonathan D; Collins, Laura C; Hu, Rong; Tamimi, Rulla M

2010-02-01

The expression of estrogen receptor-alpha (ER-alpha) and related genes has emerged as one of the major determinants of molecular classification of invasive breast cancers. Expression of a second ER, estrogen receptor-beta (ER-beta), has not been previously evaluated in a large population-based study. Therefore, we examined ER-beta expression in a large population of women with breast cancer to assess its relationship to molecular categories of invasive breast cancer. We constructed tissue microarrays from paraffin blocks of 3093 breast cancers that developed in women enrolled in the Nurses' Health Study. Tissue microarray sections were immunostained for ER-alpha, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor (EGFR) and with a monoclonal antibody to ER-beta. Cancers were categorized as luminal A (ER-alpha+ and/or PR+ and HER2-); luminal B (ER-alpha+ and/or PR+ and HER2+); HER2 (ER-alpha- and PR- and HER2+); and basal-like (ER-alpha-, PR-, HER2- and EGFR or cytokeratin 5/6+). The relationship between expression of ER-beta and molecular class of invasive breast cancer was analyzed. Overall, 68% of breast carcinomas were ER-beta+. Expression of ER-beta was significantly associated with expression of ER-alpha (P<0.0001) and PR (P<0.0001), and was inversely related to expression of HER2 (P=0.004), CK5/6 (P=0.02) and EGFR (P=0.006). Among 2170 invasive cancers with complete immunophenotypic data, 73% were luminal A, 5% luminal B, 6 % HER2 and 11% basal-like. ER-beta expression was significantly related to molecular category (P<0.0001) and was more common in luminal A (72% of cases) and B (68% of cases) than in HER2 or basal-like types. However, despite their being defined by the absence of ER-alpha expression, 55% of HER2-type and 60% of basal-like cancers showed expression of ER-beta. The role of ER-beta in the development and progression of breast cancers defined by lack of expression of ER-alpha merits further investigation.

Identification of Two Novel Endoplasmic Reticulum Body-Specific Integral Membrane Proteins1[W][OA

PubMed Central

Yamada, Kenji; Nagano, Atsushi J.; Nishina, Momoko; Hara-Nishimura, Ikuko; Nishimura, Mikio

2013-01-01

The endoplasmic reticulum (ER) body, a large compartment specific to the Brassicales, accumulates β-glucosidase and possibly plays a role in the defense against pathogens and herbivores. Although the ER body is a subdomain of the ER, it is unclear whether any ER body-specific membrane protein exists. In this study, we identified two integral membrane proteins of the ER body in Arabidopsis (Arabidopsis thaliana) and termed them MEMBRANE PROTEIN OF ENDOPLASMIC RETICULUM BODY1 (MEB1) and MEB2. In Arabidopsis, a basic helix-loop-helix transcription factor, NAI1, and an ER body component, NAI2, regulate ER body formation. The expression profiles of MEB1 and MEB2 are similar to those of NAI1, NAI2, and ER body β-glucosidase PYK10 in Arabidopsis. The expression of MEB1 and MEB2 was reduced in the nai1 mutant, indicating that NAI1 regulates the expression of MEB1 and MEB2 genes. MEB1 and MEB2 proteins localize to the ER body membrane but not to the ER network, suggesting that these proteins are specifically recruited to the ER body membrane. MEB1 and MEB2 physically interacted with ER body component NAI2, and they were diffused throughout the ER network in the nai2 mutant, which has no ER body. Heterologous expression of MEB1 and MEB2 in yeast (Saccharomyces cerevisiae) suppresses iron and manganese toxicity, suggesting that MEB1 and MEB2 are metal transporters. These results indicate that the membrane of ER bodies has specific membrane proteins and suggest that the ER body is involved in defense against metal stress as well as pathogens and herbivores. PMID:23166355

Development of a stable ERroGFP variant suitable for monitoring redox dynamics in the ER.

PubMed

Hoseki, Jun; Oishi, Asami; Fujimura, Takaaki; Sakai, Yasuyoshi

2016-01-01

The endoplasmic reticulum (ER) is an essential organelle for cellular metabolic homeostasis including folding and maturation of secretory and membrane proteins. Disruption of ER proteostasis has been implicated in the pathogenesis of various diseases such as diabetes and neurodegenerative diseases. The ER redox state, which is an oxidative environment suitable for disulfide-bond formation, is essential for ER protein quality control. Hence, detection of the ER redox state, especially in living cells, is essential to understand the mechanism by which the redox state of the ER is maintained. However, methods to detect the redox state of the ER have not been well-established because of inefficient folding and stability of roGFP variants with oxidative redox potential like roGFP-iL. Here we have improved the folding efficiency of ER-targeted roGFP-iL (ERroGFP-iL) in cells by introducing superfolder GFP (sfGFP) mutations. Four specific amino acid substitutions (S30R, Y39N, T105N and I171V) greatly improved folding efficiency in Escherichia coli and in the ER of HeLa cells, as well as the thermostability of the purified proteins. Introduction of these mutations also enhanced the dynamic range for redox change both in vitro and in the ER of living cells. ER-targeted roGFP-S4 (ERroGFP-S4) possessing these four mutations could detect physiological redox changes within the ER. ERroGFP-S4 is therefore a novel probe suitable for monitoring redox change in the ER. ERroGFP-S4 can be applied to detect aberrant ER redox states associated with various pathological conditions and to identify the mechanisms used to maintain the redox state of the ER. © 2016 The Author(s).

Eat it right: ER-phagy and recovER-phagy.

PubMed

Loi, Marisa; Fregno, Ilaria; Guerra, Concetta; Molinari, Maurizio

2018-05-25

The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and detoxification of endogenous and exogenous products. Its volume (and activity) must be maintained under normal growth conditions, must be expanded in a controlled manner on activation of ER stress programs and must be reduced to pre-stress size during the recovery phase that follows ER stress termination. ER-phagy is the constitutive or regulated fragmentation and delivery of ER fragments to lysosomal compartments for clearance. It gives essential contribution to the maintenance of cellular homeostasis, proteostasis, lipidostasis and oligosaccharidostasis (i.e. the capacity to produce the proteome, lipidome and oligosaccharidome in appropriate quality and quantity). ER turnover is activated on ER stress, nutrient deprivation, accumulation of misfolded polypeptides, pathogen attack and by activators of macroautophagy. The selectivity of these poorly characterized catabolic pathways is ensured by proteins displayed at the limiting membrane of the ER subdomain to be removed from cells. These proteins are defined as ER-phagy receptors and engage the cytosolic macroautophagy machinery via specific modules that associate with ubiquitin-like, cytosolic proteins of the Atg8/LC3/GABARAP family. In this review, we give an overview on selective ER turnover and on the yeast and mammalian ER-phagy receptors identified so far. © 2018 The Author(s).

Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels: immunohistochemical evaluations in multinodular goiter and papillary thyroid carcinoma.

PubMed

Ceresini, Graziano; Morganti, Simonetta; Graiani, Virna; Saccani, Maria; Milli, Bruna; Usberti, Elisa; Valenti, Giorgio; Ceda, Gian Paolo; Corcione, Luigi

2006-12-01

Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.

In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

PubMed

Mayock, Stephen P; Saim, Said; Fleming, Alison B

2017-12-01

Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

PubMed

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-07-25

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

78 FR 72875 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric rate filings: Docket Numbers: ER12-2145-004; ER10-2834-004; ER11-2905-003; ER11- 2904-003; ER10-2821-004; ER12-1329-002. Applicants: EC&R O&M, LLC, Munnsville Wind Farm, LLC, Pioneer Trail Wind...

Photoluminescence spectra of n-ZnO/p-GaN:(Er + Zn) and p-AlGaN:(Er + Zn) heterostructures

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

Mezdrogina, M. M., E-mail: margaret.m@mail.ioffe.ru; Krivolapchuk, V. V., E-mail: vlad.krivol@mail.ioffe.ru; Feoktistov, N. A.

2008-07-15

Luminescence intensity of heterostructures based on n-ZnO/p-GaN:(Er + Zn) and n-ZnO/AlGaN:(Er + Zn) is higher by more than an order of magnitude than the corresponding intensity of separate n-ZnO, p-GaN:(Er + Zn), and AlGaN:(Er + Zn) layers. Most likely, this phenomenon is due to the effective tunneling recombination of charge carriers caused by a decrease in the concentration of the nonradiative recombination centers located between the n-ZnO/p-GaN:(Er + Zn) and n-ZnO/AlGaN:(Er + Zn) layers.

Membrane glycerolipid equilibrium under endoplasmic reticulum stress in Arabidopsis thaliana.

PubMed

Yu, Chao-Yuan; Nguyen, Van Cam; Chuang, Ling; Kanehara, Kazue

2018-06-02

Endoplasmic reticulum (ER) is an indispensable organelle for secretory protein synthesis as well as metabolism of phospholipids and their derivatives in eukaryotic cells. Various external and internal factors may cause an accumulation of aberrant proteins in the ER, which causes ER stress and activates cellular ER stress responses to cope with the stress. In animal research, molecular mechanisms for protein quality control upon ER stress are well documented; however, how cells maintain lipid homeostasis under ER stress is an emerging issue. The ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE), two major phospholipid classes, is important under ER stress in animal cells. However, in seed plants, no study has reported on the changes in membrane lipid content under ER stress, although a number of physiologically important environmental stresses, such as heat and salinity, induce ER stress. Here, we investigated membrane glycerolipid metabolism under ER stress in Arabidopsis. ER stress transcriptionally affected PC and PE biosynthesis pathways differentially, with no significant changes in membrane glycerolipid content. Our results suggest that higher plants maintain membrane lipid equilibrium during active transcription of phospholipid biosynthetic genes under ER stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol.

PubMed

Sabo-Attwood, Tara; Kroll, Kevin J; Denslow, Nancy D

2004-04-15

The expression levels of three estrogen receptor (ER) isotypes alpha, beta, and gamma were quantified in female largemouth bass (Micropterus salmoides) (LMB) liver, ovary, brain, and pituitary tissues. ER alpha and beta expression predominated in the liver, while ERs beta and gamma predominated in the other tissues. Temporally in females, ER alpha was highly up-regulated, ER gamma was slightly up-regulated, and ER beta levels remained unchanged in the liver when plasma 17-beta estradiol (E2) and vitellogenin (Vtg) levels were elevated in the spring. In ovarian tissue from these same fish, all three ERs were maximally expressed in the fall, during early oocyte development and prior to peak plasma E2 levels. When males were injected with E2, ER alpha was highly inducible, ER gamma was moderately up-regulated, and ER beta levels were not affected. None of the ER isotypes were induced by E2 in gonadal tissues. These results combined suggest that the ERs themselves are not regulated in the same manner by E2, and furthermore, do not contribute equally to the transcriptional regulation of genes involved in fish reproduction such as Vtg.

ERMO3/MVP1/GOLD36 Is Involved in a Cell Type-Specific Mechanism for Maintaining ER Morphology in Arabidopsis thaliana

PubMed Central

Nakano, Ryohei Thomas; Matsushima, Ryo; Nagano, Atsushi J.; Fukao, Yoichiro; Fujiwara, Masayuki; Kondo, Maki; Nishimura, Mikio; Hara-Nishimura, Ikuko

2012-01-01

The endoplasmic reticulum (ER) has a unique, network-like morphology. The ER structures are composed of tubules, cisternae, and three-way junctions. This morphology is highly conserved among eukaryotes, but the molecular mechanism that maintains ER morphology has not yet been elucidated. In addition, certain Brassicaceae plants develop a unique ER-derived organelle called the ER body. This organelle accumulates large amounts of PYK10, a β-glucosidase, but its physiological functions are still obscure. We aimed to identify a novel factor required for maintaining the morphology of the ER, including ER bodies, and employed a forward-genetic approach using transgenic Arabidopsis thaliana (GFP-h) with fluorescently-labeled ER. We isolated and investigated a mutant (designated endoplasmic reticulum morphology3, ermo3) with huge aggregates and abnormal punctate structures of ER. ERMO3 encodes a GDSL-lipase/esterase family protein, also known as MVP1. Here, we showed that, although ERMO3/MVP1/GOLD36 was expressed ubiquitously, the morphological defects of ermo3 were specifically seen in a certain type of cells where ER bodies developed. Coimmunoprecipitation analysis combined with mass spectrometry revealed that ERMO3/MVP1/GOLD36 interacts with the PYK10 complex, a huge protein complex that is thought to be important for ER body-related defense systems. We also found that the depletion of transcription factor NAI1, a master regulator for ER body formation, suppressed the formation of ER-aggregates in ermo3 cells, suggesting that NAI1 expression plays an important role in the abnormal aggregation of ER. Our results suggest that ERMO3/MVP1/GOLD36 is required for preventing ER and other organelles from abnormal aggregation and for maintaining proper ER morphology in a coordinated manner with NAI1. PMID:23155454

Unraveling the estrogen receptor (er) genes in Atlantic salmon (Salmo salar) reveals expression differences between the two adult life stages but little impact from polychlorinated biphenyl (PCB) load.

PubMed

Nikoleris, Lina; Hansson, Maria C

2015-01-15

Estrogen receptors (ers) not only are activated by hormones but also interact with many human-derived environmental contaminants. Here, we present evidence for four expressed er genes in Atlantic salmon cDNA - two more ers (erα2 and erβ2) than previously published. To determine if er gene expression differs between two adult life-stages we sampled 20 adult salmon from the feeding phase in the Baltic Sea and during migration in the River Mörrum, Sweden. Results show that all four er genes are present in the investigated tissues, except for erα2 not appearing in the spleen. Overall, a profile analysis reveals the erα1 gene to be the most highly expressed er gene in both female and male Baltic Sea salmon tissues, and also in female River Mörrum salmon. In contrast, this gene has the lowest gene expression level of the four er genes in male salmon from the River Mörrum. The erα2 gene is expressed at the lowest levels in both female/male Baltic Sea salmon and in female River Mörrum salmon. Statistical analyses indicate a significant and complex interaction where both sex and adult life stage can impact er gene expression. Regression analyses did not demonstrate any significant relationship between polychlorinated biphenyl (PCB) body burden and er gene expression level, suggesting that accumulated pollutants from the Baltic Sea may be deactivated inside the salmon's lipid tissues and have limited impact on er activity. This study is the first comprehensive analysis of four er gene expression levels in two wild salmon populations from two different adult life stages where information about PCB load is also available. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

PubMed

Hayashi, Teruo; Su, Tsung-Ping

2007-11-02

Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

The sigma-1 receptor chaperone as an inter-organelle signaling modulator

PubMed Central

Su, Tsung-Ping; Hayashi, Teruo; Maurice, Tangui; Buch, Shilpa; Ruoho, Arnold E.

2010-01-01

Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intra-mitochondrial calcium (Ca2+) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca2+ homeostasis, and ER-mitochondrion-plasma membrane signaling regulates hippocampal dendritic spine formation. Here we propose that the sigma-1 receptor (Sig-1R), an ER chaperone protein, acts as an inter-organelle signaling modulator. Sig-1Rs normally reside at the ER-mitochondrion contact called the MAM (mitochondrion-associated ER membrane), where Sig-1Rs regulate ER-mitochondrion signaling and the ER-nucleus cross-talk. When cells are stimulated by ligands or undergo prolonged stress, Sig-1Rs translocate from the MAM to the ER reticular network and plasmalemma/plasma membrane to regulate a variety of functional proteins, including ion channels, receptors, and kinases. Thus, the Sig-1R serves as an inter-organelle signaling modulator locally at the MAM and remotely at the plasmalemma/plasma membrane. Many pharmacological/physiological effects of Sig-1Rs may relate to this unique action of Sig-1Rs. PMID:20869780

Influence of estrogen receptor status on dietary risk factors for breast cancer.

PubMed Central

Hislop, T G; Kan, L; Coldman, A J; Band, P R; Brauer, G

1988-01-01

It has been suggested that the relation between diet and breast cancer may depend on estrogen receptor (ER) status. We examined the responses to a self-administered questionnaire on frequency of consumption of various foods by 493 women with breast cancer (160 with ER-negative tumours and 333 with ER-positive tumours) and 527 controls whose menopausal status was known. Analysis of the reported consumption of foods selected for their fat or carotene content showed no clear distinction in dietary factors between the ER-negative and ER-positive groups. Frequent consumption of meat fats generally increased the risk of both ER-negative and ER-positive tumours; there were no clear trends in risk associated with vegetable consumption for either ER group. Fish was the only item affecting the risk for ER-negative and ER-positive tumours differently, frequent consumption reducing the risk for the former (p = 0.02). The results do not support the hypothesis that ER status influences the relation between dietary fat consumption and risk of breast cancer. PMID:3342359

ER trapping reveals Golgi enzymes continually revisit the ER through a recycling pathway that controls Golgi organization

PubMed Central

Sengupta, Prabuddha; Satpute-Krishnan, Prasanna; Seo, Arnold Y.; Burnette, Dylan T.; Patterson, George H.; Lippincott-Schwartz, Jennifer

2015-01-01

Whether Golgi enzymes remain localized within the Golgi or constitutively cycle through the endoplasmic reticulum (ER) is unclear, yet is important for understanding Golgi dependence on the ER. Here, we demonstrate that the previously reported inefficient ER trapping of Golgi enzymes in a rapamycin-based assay results from an artifact involving an endogenous ER-localized 13-kD FK506 binding protein (FKBP13) competing with the FKBP12-tagged Golgi enzyme for binding to an FKBP-rapamycin binding domain (FRB)-tagged ER trap. When we express an FKBP12-tagged ER trap and FRB-tagged Golgi enzymes, conditions precluding such competition, the Golgi enzymes completely redistribute to the ER upon rapamycin treatment. A photoactivatable FRB-Golgi enzyme, highlighted only in the Golgi, likewise redistributes to the ER. These data establish Golgi enzymes constitutively cycle through the ER. Using our trapping scheme, we identify roles of rab6a and calcium-independent phospholipase A2 (iPLA2) in Golgi enzyme recycling, and show that retrograde transport of Golgi membrane underlies Golgi dispersal during microtubule depolymerization and mitosis. PMID:26598700

78 FR 69661 - Notice of FERC Staff Attendance at the Entergy Regional State Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

.... ER12-1384 Entergy Gulf States Docket No. ER12-1385 Louisiana, L.L.C. Entergy Louisiana, LLC... Arkansas, Inc........ Docket No. ER13-1508 Entergy Gulf States Docket No. ER13-1509 Louisiana, L.L.C... Arkansas, Inc........ Docket No. ER14-75 Entergy Gulf States Docket No. ER14-76 Louisiana, L.L.C. Entergy...

Is quantitative oestrogen receptor expression useful in the evaluation of the clinical prognosis? Analysis of a homogeneous series of 797 patients with prospective determination of the ER status using simultaneous EIA and IHC.

PubMed

Mazouni, Chafika; Bonnier, Pascal; Goubar, Aïcha; Romain, Sylvie; Martin, Pierre-Marie

2010-10-01

Oestrogen receptor (ER) determination in breast cancer (BC) is a major yardstick for the prognosis and for response to hormonal therapy (HT). As several techniques have been proposed for ER quantification, the purpose of our study was to assess whether the qualitative or quantitative analysis of ER expression might influence the prognosis and response to treatment. We analysed overall survival (OS) and disease-free survival (DFS) in 797 primary BC cases with ER determination by enzyme immunoassay (EIA) and immunohistochemistry (IHC). The clinical impact according to qualitative or quantitative analysis of ER expression was assessed. Response to HT was evaluated according to quantitative EIA-determined ER expression levels. According to the qualitative analysis of ER expression, patients with EIA-determined and IHC-determined ER-positive tumours had significantly longer OS and DFS (p<0.001). The analysis stratified on quartiles of ER levels showed significantly different outcomes according to EIA- and IHC-determined subgroups. In the group of patients who received adjuvant treatment, 5-year OS was significantly different between the groups, with a clear benefit for the highest EIA-determined ER quartiles (p<0.001). Comparatively, in terms of 5-year DFS, a clear separation was noted between groups for adjuvant treatment (p<0.001). The group with moderate ER+ values was clearly distinct from the ER-negative population. Quantitative ER expression helped to better distinguish the beneficial or detrimental effect of HT within quartiles of ER-expressing tumours. Based on the STEPP analysis which showed a trend towards an ER effect on DFS as a function of HT assignment, we confirm the benefit of HT in patients with a very high EIA-determined ER level and a detrimental impact on negative and weakly positive groups. Quantitative ER expression in BC helps to better discriminate heterogeneity in clinical outcome and response to HT. Copyright © 2010 Elsevier Ltd. All rights reserved.

US Army Research Laboratory Directed Energy Internship Program 2014

DTIC Science & Technology

2015-11-01

7 1400–1800 nm. However, when making EDFs, the solubility of Er in traditional silica ( SiO2 )-based glass is low and the ions that successfully...Thus, either half or all of the energy in a pair of excited ions could be wasted. In traditional SiO2 -based Er-doped glass (Er-SD), Er is co-doped...upconversion, Er-doped SiO2 NPs (Er-NP) are doped into the glass core of a fiber. This process is thought to create a cage of Al and O ions around each Er

Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells.

PubMed

Dejeans, Nicolas; Tajeddine, Nicolas; Beck, Raphaël; Verrax, Julien; Taper, Henryk; Gailly, Philippe; Calderon, Pedro Buc

2010-05-01

Increase in cytosolic calcium concentration ([Ca2+](c)), release of endoplasmic reticulum (ER) calcium ([Ca2+](er)) and ER stress have been proposed to be involved in oxidative toxicity. Nevertheless, their relative involvements in the processes leading to cell death are not well defined. In this study, we investigated whether oxidative stress generated during ascorbate-driven menadione redox cycling (Asc/Men) could trigger these three events, and, if so, whether they contributed to Asc/Men cytoxicity in MCF-7 cells. Using microspectrofluorimetry, we demonstrated that Asc/Men-generated oxidative stress was associated with a slow and moderate increase in [Ca2+](c), largely preceding permeation of propidium iodide, and thus cell death. Asc/Men treatment was shown to partially deplete ER calcium stores after 90 min (decrease by 45% compared to control). This event was associated with ER stress activation, as shown by analysis of eIF2 phosphorylation and expression of the molecular chaperone GRP94. Thapsigargin (TG) was then used to study the effect of complete [Ca2+](er) emptying during the oxidative stress generated by Asc/Men. Surprisingly, the combination of TG and Asc/Men increased ER stress to a level considerably higher than that observed for either treatment alone, suggesting that [Ca2+](er) release alone is not sufficient to explain ER stress activation during oxidative stress. Finally, TG-mediated [Ca2+](er) release largely potentiated ER stress, DNA fragmentation and cell death caused by Asc/Men, supporting a role of ER stress in the process of Asc/Men cytotoxicity. Taken together, our results highlight the involvement of ER stress and [Ca2+](er) decrease in the process of oxidative stress-induced cell death in MCF-7 cells. 2009 Elsevier Inc. All rights reserved.

Palmitate induces cisternal ER expansion via the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells.

PubMed

Kim, Seong Keun; Oh, Eunhye; Yun, Mihee; Lee, Seong-Beom; Chae, Gue Tae

2015-07-16

Endoplasmic reticulum (ER) stress induces ER expansion. The expansion of the intracisternal space of the ER was found in macrophages associated with human atherosclerotic lesions. We also previously reported that palmitate induces cisternal ER expansion and necrosis in RAW 264.7 cells. In this study, we report on an investigation of the likely mechanism responsible for this palmitate-induced cisternal ER expansion in a mouse macrophage cell line, RAW 264.7 cells. RAW 264.7 cells were pre-treated with the designated inhibitor or siRNA, followed by treatment with palmitate. Changes in the ER structure were examined by transmission electron microscopy. The induction of ER stress was confirmed by an increase in the extent of phosphorylation of PERK, the expression of BiP and CHOP, and the splicing of XBP-1 mRNA. Phospholipid staining was performed with the LipidTOX Red phospholipidosis detection reagent. Related gene expressions were detected by quantitative real time-RT-PCR or RT-PCR. Palmitate was found to induce ER stress and cisternal ER expansion. In addition, palmitate-induced cisternal ER expansion was attenuated by ER stress inhibitors, such as 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA). The findings also show that palmitate induced-mRNA expression of CCTα, which increases phospholipid synthesis, was attenuated by the down-regulation of XBP-1, a part of ER stress. Furthermore, palmitate-induced phospholipid accumulation and cisternal ER expansion were attenuated by the down-regulation of XBP-1 or CCTα. The findings reported herein indicate that palmitate-induced cisternal ER expansion is dependent on the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells.

Phosphorylation of ETS Transcription Factor ER81 in a Complex with Its Coactivators CREB-Binding Protein and p300

PubMed Central

Papoutsopoulou, Stamatia; Janknecht, Ralf

2000-01-01

The ETS protein ER81 is a DNA-binding factor capable of enhancing gene transcription and is implicated in cellular transformation, but presently the mechanisms of its actions are unclear. In this report, ER81 is shown to coimmunoprecipitate with the transcriptional coactivator CREB-binding protein (CBP) and the related p300 protein (together referred to as CBP/p300). Moreover, confocal laser microscopic studies demonstrated that ER81 and p300 colocalized to nuclear speckles. In vitro and in vivo interaction studies revealed that ER81 amino acids 249 to 429, which encompass the ETS DNA-binding domain, are responsible for binding to CBP/p300. However, mutation of a putative protein-protein interaction motif, LXXLL, in the ETS domain of ER81 did not affect interaction with CBP/p300, whereas DNA binding of ER81 was abolished. Furthermore, two regions within CBP, amino acids 451 to 721 and 1891 to 2175, are capable of binding to ER81. Consistent with the physical interaction between ER81 and the coactivators CBP and p300, ER81 transcriptional activity was potentiated by CBP/p300 overexpression. Moreover, an ER81-associated protein kinase activity was enhanced upon p300 overexpression. This protein kinase phosphorylates ER81 on serines 191 and 216, and mutation of these phosphorylation sites increased ER81 transcriptional activity in Mv1Lu cells but not in HeLa cells. Altogether, our data elucidate the mechanism of how ER81 regulates gene transcription, through interaction with the coactivators CBP and p300 and an associated kinase that may cell type specifically modulate the ability of ER81 to activate gene transcription. PMID:10982847

Endoplasmic reticulum membrane potassium channel dysfunction in high fat diet induced stress in rat hepatocytes

PubMed Central

Khodaee, Naser; Ghasemi, Maedeh; Saghiri, Reza; Eliassi, Afsaneh

2014-01-01

In a previous study we reported the presence of a large conductance K+ channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 µM and tolbutamide 400 µM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K+ channel. Our results indicate that the channel Po was significantly increased at voltages above +30 mV. Interestingly, addition of ATP 7.5 mM, glibenclamide 400 µM and tolbutamide 2400 µM totally inhibited the channel activities, 3-fold, 4-fold and 6-fold higher than that in the control groups, respectively. Our results thus demonstrate a modification in the ER K+ channel gating properties and decreased sensitivity to drugs in membrane preparations coming from ER high fat model of ER stress, an effect potentially linked to a change in ER K+ channel subunits in ER stress condition. Our results may provide new insights into the cellular mechanisms underlying ER dysfunctions in ER stress. PMID:26417322

Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction.

PubMed

Fu, Hai Ying; Sanada, Shoji; Matsuzaki, Takashi; Liao, Yulin; Okuda, Keiji; Yamato, Masaki; Tsuchida, Shota; Araki, Ryo; Asano, Yoshihiro; Asanuma, Hiroshi; Asakura, Masanori; French, Brent A; Sakata, Yasushi; Kitakaze, Masafumi; Minamino, Tetsuo

2016-03-04

Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane-resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. Doxorubicin activated the ER stress-initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment. © 2016 American Heart Association, Inc.

Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling.

PubMed

Kang, Lianguo; Zhang, Xintian; Xie, Yan; Tu, Yaping; Wang, Dong; Liu, Zhenming; Wang, Zhao-Yi

2010-04-01

Accumulating evidence suggested that an orphan G protein-coupled receptor (GPR)30, mediates nongenomic responses to estrogen. The present study was performed to investigate the molecular mechanisms underlying GPR30 function. We found that knockdown of GPR30 expression in breast cancer SK-BR-3 cells down-regulated the expression levels of estrogen receptor (ER)-alpha36, a variant of ER-alpha. Introduction of a GPR30 expression vector into GPR30 nonexpressing cells induced endogenous ER-alpha36 expression, and cotransfection assay demonstrated that GPR30 activated the promoter activity of ER-alpha36 via an activator protein 1 binding site. Both 17beta-estradiol (E2) and G1, a compound reported to be a selective GPR30 agonist, increased the phosphorylation levels of the MAPK/ERK1/2 in SK-BR-3 cells, which could be blocked by an anti-ER-alpha36-specific antibody against its ligand-binding domain. G1 induced activities mediated by ER-alpha36, such as transcription activation activity of a VP16-ER-alpha36 fusion protein and activation of the MAPK/ERK1/2 in ER-alpha36-expressing cells. ER-alpha36-expressing cells, but not the nonexpressing cells, displayed high-affinity, specific E2 and G1 binding, and E2- and G1-induced intracellular Ca(2+) mobilization only in ER-alpha36 expressing cells. Taken together, our results demonstrated that previously reported activities of GPR30 in response to estrogen were through its ability to induce ER-alpha36 expression. The selective G protein-coupled receptor (GPR)30 agonist G1 actually interacts with ER-alpha36. Thus, the ER-alpha variant ER-alpha36, not GPR30, is involved in nongenomic estrogen signaling.

Human MI-ER1 Alpha and Beta Function as Transcriptional Repressors by Recruitment of Histone Deacetylase 1 to Their Conserved ELM2 Domain

PubMed Central

Ding, Zhihu; Gillespie, Laura L.; Paterno, Gary D.

2003-01-01

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3′ end of hmi-er1 produces two major isoforms, hMI-ER1α and hMI-ER1β, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1α and hMI-ER1β in the regulation of transcription. Using fusion proteins of hMI-ER1α or hMI-ER1β tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1α and hMI-ER1β occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription. PMID:12482978

Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.

PubMed

Ding, Zhihu; Gillespie, Laura L; Paterno, Gary D

2003-01-01

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3' end of hmi-er1 produces two major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Using fusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.

Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

PubMed Central

Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

2017-01-01

The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

TaER Expression Is Associated with Transpiration Efficiency Traits and Yield in Bread Wheat

PubMed Central

Zheng, Jiacheng; Yang, Zhiyuan; Madgwick, Pippa J.; Carmo-Silva, Elizabete; Parry, Martin A. J.; Hu, Yin-Gang

2015-01-01

ERECTA encodes a receptor-like kinase and is proposed as a candidate for determining transpiration efficiency of plants. Two genes homologous to ERECTA in Arabidopsis were identified on chromosomes 6 (TaER2) and 7 (TaER1) of bread wheat (Triticum aestivum L.), with copies of each gene on the A, B and D genomes of wheat. Similar expression patterns were observed for TaER1 and TaER2 with relatively higher expression of TaER1 in flag leaves of wheat at heading (Z55) and grain-filling (Z73) stages. Significant variations were found in the expression levels of both TaER1 and TaER2 in the flag leaves at both growth stages among 48 diverse bread wheat varieties. Based on the expression of TaER1 and TaER2, the 48 wheat varieties could be classified into three groups having high (5 varieties), medium (27 varieties) and low (16 varieties) levels of TaER expression. Significant differences were also observed between the three groups varying for TaER expression for several transpiration efficiency (TE)- related traits, including stomatal density (SD), transpiration rate, photosynthetic rate (A), instant water use efficiency (WUEi) and carbon isotope discrimination (CID), and yield traits of biomass production plant-1 (BYPP) and grain yield plant-1 (GYPP). Correlation analysis revealed that the expression of TaER1 and TaER2 at the two growth stages was significantly and negatively associated with SD (P<0.01), transpiration rate (P<0.05) and CID (P<0.01), while significantly and positively correlated with flag leaf area (FLA, P<0.01), A (P<0.05), WUEi (P<0.05), BYPP (P<0.01) and GYPP (P<0.01), with stronger correlations for TaER1 than TaER2 and at grain-filling stage than at heading stage. These combined results suggested that TaER involved in development of transpiration efficiency -related traits and yield in bread wheat, implying a function for TaER in regulating leaf development of bread wheat and contributing to expression of these traits. Moreover, the results indicate that TaER could be exploitable for manipulating important agronomical traits in wheat improvement. PMID:26047019

TaER Expression Is Associated with Transpiration Efficiency Traits and Yield in Bread Wheat.

PubMed

Zheng, Jiacheng; Yang, Zhiyuan; Madgwick, Pippa J; Carmo-Silva, Elizabete; Parry, Martin A J; Hu, Yin-Gang

2015-01-01

ERECTA encodes a receptor-like kinase and is proposed as a candidate for determining transpiration efficiency of plants. Two genes homologous to ERECTA in Arabidopsis were identified on chromosomes 6 (TaER2) and 7 (TaER1) of bread wheat (Triticum aestivum L.), with copies of each gene on the A, B and D genomes of wheat. Similar expression patterns were observed for TaER1 and TaER2 with relatively higher expression of TaER1 in flag leaves of wheat at heading (Z55) and grain-filling (Z73) stages. Significant variations were found in the expression levels of both TaER1 and TaER2 in the flag leaves at both growth stages among 48 diverse bread wheat varieties. Based on the expression of TaER1 and TaER2, the 48 wheat varieties could be classified into three groups having high (5 varieties), medium (27 varieties) and low (16 varieties) levels of TaER expression. Significant differences were also observed between the three groups varying for TaER expression for several transpiration efficiency (TE)- related traits, including stomatal density (SD), transpiration rate, photosynthetic rate (A), instant water use efficiency (WUEi) and carbon isotope discrimination (CID), and yield traits of biomass production plant-1 (BYPP) and grain yield plant-1 (GYPP). Correlation analysis revealed that the expression of TaER1 and TaER2 at the two growth stages was significantly and negatively associated with SD (P<0.01), transpiration rate (P<0.05) and CID (P<0.01), while significantly and positively correlated with flag leaf area (FLA, P<0.01), A (P<0.05), WUEi (P<0.05), BYPP (P<0.01) and GYPP (P<0.01), with stronger correlations for TaER1 than TaER2 and at grain-filling stage than at heading stage. These combined results suggested that TaER involved in development of transpiration efficiency -related traits and yield in bread wheat, implying a function for TaER in regulating leaf development of bread wheat and contributing to expression of these traits. Moreover, the results indicate that TaER could be exploitable for manipulating important agronomical traits in wheat improvement.

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

PubMed Central

Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

2017-01-01

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function. DOI: http://dx.doi.org/10.7554/eLife.23882.001 PMID:28742022

Endoplasmic Reticulum Stress in Beta Cells and Development of Diabetes

PubMed Central

Fonseca, Sonya G.; Burcin, Mark; Gromada, Jesper; Urano, Fumihiko

2009-01-01

The endoplasmic reticulum (ER) is a cellular compartment responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. A myriad of pathological and physiological factors perturb ER function and cause dysregulation of ER homeostasis, leading to ER stress. ER stress elicits a signaling cascade to mitigate stress, the Unfolded Protein Response (UPR). As long as the UPR can relieve stress, cells can produce the proper amount of proteins and maintain ER homeostasis. If the UPR, however, fails to maintain ER homeostasis, cells will undergo apoptosis. Activation of the UPR is critical to the survival of insulin-producing pancreatic β-cells with high secretory protein production. Any disruption of ER homeostasis in β-cells can lead to cell death and contribute to the pathogenesis of diabetes. There are several models of ER stress-mediated diabetes. In this review, we outline the underlying molecular mechanisms of ER stress-mediated β-cell dysfunction and death during the progression of diabetes. PMID:19665428

Integrated self-organization of transitional ER and early Golgi compartments.

PubMed

Glick, Benjamin S

2014-02-01

COPII coated vesicles bud from an ER domain termed the transitional ER (tER), but the mechanism that clusters COPII vesicles at tER sites is unknown. tER sites are closely associated with early Golgi or pre-Golgi structures, suggesting that the clustering of nascent COPII vesicles could be achieved by tethering to adjacent membranes. This model challenges the prevailing view that COPII vesicles are clustered by a scaffolding protein at the ER surface. Although Sec16 was proposed to serve as such a scaffolding protein, recent data suggest that rather than organizing COPII into higher-order structures, Sec16 acts at the level of individual COPII vesicles to regulate COPII turnover. A plausible synthesis is that tER sites are created by tethering to Golgi membranes and are regulated by Sec16. Meanwhile, the COPII vesicles that bud from tER sites are thought to nucleate new Golgi cisternae. Thus, an integrated self-organization process may generate tER-Golgi units. © 2014 WILEY Periodicals, Inc.

Upconversion luminescence of CsScF4 crystals doped with erbium and ytterbium

NASA Astrophysics Data System (ADS)

Ikonnikov, D. A.; Voronov, V. N.; Molokeev, M. S.; Aleksandrovsky, A. S.

2016-10-01

Tetragonal CsScF4 crystals doped with (5 at.%) Er and Er/Yb (0.5 at.%/5 at.%) are grown and their crystal structure is determined to belong to Pmmn space group. Er and Yb ions are shown to occupy distorted octahedral Sc sites with the center of inversion. Bright visible upconversion luminescence was observed under 970-980 nm pumping with red (4F9/2), yellow (4S3/2) and green (2H11/2) bands of comparable intensity. UCL tuning curves maximize at 972 nm (CSF:Er) and at 969.7 nm (CSF:Er,Yb) pumping wavelengths. Different ratios between yellow-green and red luminescence intensities in CSF:Er and CSF:Er, Yb are explained by contribution of cross-relaxation in CSF:Er UCL. UC in CSF:Er is a three stage process while UC in CSF:Er, Yb is a two stage process. The peculiarities of power dependences are explained by the power-dependent repopulation between starting levels of UC.

A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.

PubMed

Joshi, Amit S; Huang, Xiaofang; Choudhary, Vineet; Levine, Tim P; Hu, Junjie; Prinz, William A

2016-11-21

Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like proteins that help maintain ER structure by stabilizing high membrane curvature in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has dramatically altered ER morphology. We found that ER shape is restored in this mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate membranes both in cells and when reconstituted into proteoliposomes, indicating that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p is low abundance, and we found that it localizes to subdomains in the ER. We show that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs) are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p help shape and generate regions of the ER where PPV biogenesis occurs.

STRUCTURAL HETEROGENEITIES AND PALEO FLUID FLOW IN AN ANALOG SANDSTONE RESERVOIR 2001-2004

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

Pollard, David; Aydin, Atilla

2005-02-22

Fractures and faults are brittle structural heterogeneities that can act both as conduits and barriers with respect to fluid flow in rock. This range in the hydraulic effects of fractures and faults greatly complicates the challenges faced by geoscientists working on important problems: from groundwater aquifer and hydrocarbon reservoir management, to subsurface contaminant fate and transport, to underground nuclear waste isolation, to the subsurface sequestration of CO2 produced during fossil-fuel combustion. The research performed under DOE grant DE-FG03-94ER14462 aimed to address these challenges by laying a solid foundation, based on detailed geological mapping, laboratory experiments, and physical process modeling, onmore » which to build our interpretive and predictive capabilities regarding the structure, patterns, and fluid flow properties of fractures and faults in sandstone reservoirs. The material in this final technical report focuses on the period of the investigation from July 1, 2001 to October 31, 2004. The Aztec Sandstone at the Valley of Fire, Nevada, provides an unusually rich natural laboratory in which exposures of joints, shear deformation bands, compaction bands and faults at scales ranging from centimeters to kilometers can be studied in an analog for sandstone aquifers and reservoirs. The suite of structures there has been documented and studied in detail using a combination of low-altitude aerial photography, outcrop-scale mapping and advanced computational analysis. In addition, chemical alteration patterns indicative of multiple paleo fluid flow events have been mapped at outcrop, local and regional scales. The Valley of Fire region has experienced multiple episodes of fluid flow and this is readily evident in the vibrant patterns of chemical alteration from which the Valley of Fire derives its name. We have successfully integrated detailed field and petrographic observation and analysis, process-based mechanical modeling, and numerical simulation of fluid flow to study a typical sandstone aquifer/reservoir at a variety of scales. We have produced many tools and insights which can be applied to active subsurface flow systems and practical problems of pressing global importance.« less

77 FR 15638 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...We are revising an earlier proposed airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, - 900 and -900ER series airplanes. That NPRM proposed to require modifying the fluid drain path in the wing leading edge area, forward of the wing front spar, and doing all applicable related investigative and corrective actions. That NPRM was prompted by a report of leaking fuel from the wing leading edge area at the inboard end of the number 5 leading edge slat. This action revises that NPRM by including installing new seal disks on the latches in the fuel shutoff valve access door as part of the modification and by specifying that certain inspections are detailed inspections. This action also revises the applicability to include additional airplanes. We are proposing this AD to prevent flammable fluids from accumulating in the wing leading edge, and draining inboard and onto the engine exhaust nozzle, which could result in a fire. Since these actions impose an additional burden over that proposed in the NPRM, we are reopening the comment period to allow the public the chance to comment on these proposed changes.

Combining autophagy-inducing peptides and brefeldin A delivered by perinuclear-localized mesoporous silica nanoparticles: a manipulation strategy for ER-phagy.

PubMed

Wang, Yimin; Zhao, Zhao; Wei, Fujing; Luo, Zewei; Duan, Yixiang

2018-05-10

Autophagic degradation of the endoplasmic reticulum (ER-phagy) has been found to play a critical role in human sensory neuropathy. So far, however, specific and efficient intervention means for ER-phagy remain unexplored. Herein, brefeldin A (BFA), a blocking agent on protein transport between the ER and Golgi, was screened from ER stress inducers. BFA was then delivered to the perinuclear area co-localized with the ER by a mesoporous silica nanoparticle-based drug-carrier functionalized with autophagy-inducing peptides of TAT-beclin 1 (MSNs-BFA), to evoke a perturbation of ER-phagy. The molecular mechanism of ER-phagy regulated by BFA was explored by biochemical evaluation including time-lapse live-cell fluorescence imaging. We found that MSNs-BFA treatment caused a lower mRNA/protein expression level of FAM134b even under a compensation of autophagic flux in U2OS cells, and resulted in ER-expansion. The fragmentation of the ER was blocked as a response to ER stress mediated by inactivation of the AKT/TSC/mTOR pathway. Our work developed an efficient external manipulation strategy to regulate ER-phagy and may contribute to the therapeutic application of autophagy-related major human diseases.

COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis.

PubMed

Fang, Jingye; Liu, Ming; Zhang, Xuebao; Sakamoto, Takeshi; Taatjes, Douglas J; Jena, Bhanu P; Sun, Fei; Woods, James; Bryson, Tim; Kowluru, Anjaneyulu; Zhang, Kezhong; Chen, Xuequn

2015-08-01

Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death. Among the 4 components to maintain ER homeostasis in β-cells, the role of ER export in insulin biogenesis is the least understood. To address this knowledge gap, the present study investigated the molecular mechanism of proinsulin ER export in MIN6 cells and primary islets. Two inhibitory mutants of the secretion-associated RAS-related protein (Sar)1 small GTPase, known to specifically block coat protein complex II (COPII)-dependent ER export, were overexpressed in β-cells using recombinant adenoviruses. Results from this approach, as well as small interfering RNA-mediated Sar1 knockdown, demonstrated that defective Sar1 function blocked proinsulin ER export and abolished its conversion to mature insulin in MIN6 cells, isolated mouse, and human islets. It is further revealed, using an in vitro vesicle formation assay, that proinsulin was packaged into COPII vesicles in a GTP- and Sar1-dependent manner. Blockage of COPII-dependent ER exit by Sar1 mutants strongly induced ER morphology change, ER stress response, and β-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (p-eIF2α) and inositol-requiring protein 1 (IRE1)/x-box binding protein 1 (Xbp1) pathways but not via activating transcription factor 6 (ATF6). Collectively, results from the study demonstrate that COPII-dependent ER export plays a vital role in insulin biogenesis, ER homeostasis, and β-cell survival.

Tributyltin-induced endoplasmic reticulum stress and its Ca{sup 2+}-mediated mechanism

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

Isomura, Midori; Kotake, Yaichiro, E-mail: yaichiro@hiroshima-u.ac.jp; Masuda, Kyoichi

2013-10-01

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca{sup 2+} signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca{sup 2+} homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700 nM TBT induced ER stress markers suchmore » as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca{sup 2+} depletion, and to test this idea, we examined the effect of TBT on intracellular Ca{sup 2+} concentration using fura-2 AM, a Ca{sup 2+} fluorescent probe. TBT increased intracellular Ca{sup 2+} concentration in a TBT-concentration-dependent manner, and Ca{sup 2+} increase in 700 nM TBT was mainly blocked by 50 μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca{sup 2+} concentration by releasing Ca{sup 2+} from ER, thereby causing ER stress. - Highlights: • We established that tributyltin induces endoplasmic reticulum (ER) stress. • Tributyltin induces ER stress markers in a concentration-dependent manner. • Tributyltin increases Ca{sup 2+} release from ER, thereby causing ER stress. • Dibutyltin and monobutyltin did not increase GRP78 or intracellular Ca{sup 2+}.« less

78 FR 28212 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

...; ER10- 2504-004; ER12-610-004; ER13-338-002. Applicants: Catalina Solar, LLC, Oasis Power Partners, LLC.... Docket Numbers: ER13-1398-000. Applicants: Fairless Energy, LLC, Dominion Bridgeport Fuel Cell, LLC.... ET 5/23/13. Docket Numbers: ER13-1403-000. Applicants: Dominion Bridgeport Fuel Cell, LLC...

36 CFR 1200.7 - What are NARA logos and how are they used?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Originals; ER11MY04.002 (4) Electronic Records Archives; ER11MY04.003 (5) The Archival Research Catalog; ER11MY04.004 (6) The Archives Library Information Center; ER11MY04.005 (7) Presidential Libraries; ER11MY04...

36 CFR 1200.7 - What are NARA logos and how are they used?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Originals; ER11MY04.002 (4) Electronic Records Archives; ER11MY04.003 (5) The Archival Research Catalog; ER11MY04.004 (6) The Archives Library Information Center; ER11MY04.005 (7) Presidential Libraries; ER11MY04...

49 CFR Appendix A to Subpart V of... - Figures

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013 ER23JN09.005...

49 CFR Appendix A to Subpart V of... - Figures

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part 572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013 ER23JN09...

49 CFR Appendix A to Subpart V of... - Figures

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part 572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013 ER23JN09...

The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

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

Warner, Margaret; Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX; Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@mednut.ki.se

2010-05-21

The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role ofmore » ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.« less

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

PubMed

Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

2009-11-30

Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

Fluorescence lifetime imaging of microviscosity changes during ER autophagy in live cells

NASA Astrophysics Data System (ADS)

He, Ying; Samanta, Soham; Gong, Wanjun; Liu, Wufan; Pan, Wenhui; Yang, Zhigang; Qu, Junle

2018-02-01

Unfolded or misfolded protein accumulation inside Endoplasmic Reticulum (ER) will cause ER stress and subsequently will activate cellular autophagy to release ER stress, which would ultimately result in microviscosity changes. However, even though, it is highly significant to gain a quantitative assessment of microviscosity changes during ER autophagy to study ER stress and autophagy behaviors related diseases, it has rarely been reported yet. In this work, we have reported a BODIPY based fluorescent molecular rotor that can covalently bind with vicinal dithiols containing nascent proteins in ER and hence can result in ER stress through the inhibition of the folding of nascent proteins. The change in local viscosity, caused by the release of the stress in cells through autophagy, was quantified by the probe using fluorescence lifetime imaging. This work basically demonstrates the possibility of introducing synthetic chemical probe as a promising tool to diagnose ER-viscosity-related diseases.

Endoplasmic Reticulum Stress and Lipid Metabolism: Mechanisms and Therapeutic Potential

PubMed Central

Basseri, Sana; Austin, Richard C.

2012-01-01

The endoplasmic reticulum (ER) plays a crucial role in protein folding, assembly, and secretion. Disruption of ER homeostasis may lead to accumulation of misfolded or unfolded proteins in the ER lumen, a condition referred to as ER stress. In response to ER stress, a signal transduction pathway known as the unfolded protein response (UPR) is activated. UPR activation allows the cell to cope with an increased protein-folding demand on the ER. Recent studies have shown that ER stress/UPR activation plays a critical role in lipid metabolism and homeostasis. ER-stress-dependent dysregulation of lipid metabolism may lead to dyslipidemia, insulin resistance, cardiovascular disease, type 2 diabetes, and obesity. In this paper, we examine recent findings illustrating the important role ER stress/UPR signalling pathways play in regulation of lipid metabolism, and how they may lead to dysregulation of lipid homeostasis. PMID:22195283

ER sheet persistence is coupled to myosin 1c–regulated dynamic actin filament arrays

PubMed Central

Joensuu, Merja; Belevich, Ilya; Rämö, Olli; Nevzorov, Ilya; Vihinen, Helena; Puhka, Maija; Witkos, Tomasz M.; Lowe, Martin; Vartiainen, Maria K.; Jokitalo, Eija

2014-01-01

The endoplasmic reticulum (ER) comprises a dynamic three-dimensional (3D) network with diverse structural and functional domains. Proper ER operation requires an intricate balance within and between dynamics, morphology, and functions, but how these processes are coupled in cells has been unclear. Using live-cell imaging and 3D electron microscopy, we identify a specific subset of actin filaments localizing to polygons defined by ER sheets and tubules and describe a role for these actin arrays in ER sheet persistence and, thereby, in maintenance of the characteristic network architecture by showing that actin depolymerization leads to increased sheet fluctuation and transformations and results in small and less abundant sheet remnants and a defective ER network distribution. Furthermore, we identify myosin 1c localizing to the ER-associated actin filament arrays and reveal a novel role for myosin 1c in regulating these actin structures, as myosin 1c manipulations lead to loss of the actin filaments and to similar ER phenotype as observed after actin depolymerization. We propose that ER-associated actin filaments have a role in ER sheet persistence regulation and thus support the maintenance of sheets as a stationary subdomain of the dynamic ER network. PMID:24523293

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

PubMed

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-04-01

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Local Anaesthetic Infiltration and Indwelling Postoperative Wound Catheters for Patients with Hip Fracture Reduce Death Rates and Length of Stay

PubMed Central

Harrison, William D.; Lees, Deborah; A'Court, Jamie; Ankers, Thomas; Harper, Ian; Inman, Dominic; Reed, Mike R.

2015-01-01

Background. An analgesic enhanced recovery (ER) protocol for patients with a hip fracture was introduced. It was hypothesised that the ER would reduce pain, length of stay and improve clinical outcomes. The protocol used intraoperative infiltration of levobupivacaine followed by ongoing wound infusions. Methods. Consecutive patients admitted to two hospitals were eligible for the ER protocol. Numerical Reporting Scale pain scores (0–10) were recorded alongside opiate requirements. 434 patients in the ER group (316 full ER, 90 partial ER, and 28 no ER) were compared to a control group (CG) of 100 consecutive patients managed with traditional opiate analgesia. Results. Mean opiate requirement was 49.2 mg (CG) versus 32.5 mg (ER). Pain scores were significantly reduced in the full ER group, p < 0.0001. Direct discharge home and mean acute inpatient stay were significantly reduced (p = 0.0031 and p < 0.0001, resp.). 30-day mortality was 15% (CG) versus 5.5% (ER), p = 0.0024. Conclusions. This analgesic ER protocol for patients with a hip fracture was safe and effective and was associated with reduced inpatient stay and mortality. PMID:26649330

The endoplasmic reticulum in plant immunity and cell death

PubMed Central

Eichmann, Ruth; Schäfer, Patrick

2012-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells and a major production site of proteins destined for vacuoles, the plasma membrane, or apoplast in plants. At the ER, these secreted proteins undergo multiple processing steps, which are supervised and conducted by the ER quality control system. Notably, processing of secreted proteins can considerably elevate under stress conditions and exceed ER folding capacities. The resulting accumulation of unfolded proteins is defined as ER stress. The efficiency of cells to re-establish proper ER function is crucial for stress adaptation. Besides delivering proteins directly antagonizing and resolving stress conditions, the ER monitors synthesis of immune receptors. This indicates the significance of the ER for the establishment and function of the plant immune system. Recent studies point out the fragility of the entire system and highlight the ER as initiator of programed cell death (PCD) in plants as was reported for vertebrates. This review summarizes current knowledge on the impact of the ER on immune and PCD signaling. Understanding the integration of stress signals by the ER bears a considerable potential to optimize development and to enhance stress resistance of plants. PMID:22936941

The endoplasmic reticulum in plant immunity and cell death.

PubMed

Eichmann, Ruth; Schäfer, Patrick

2012-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells and a major production site of proteins destined for vacuoles, the plasma membrane, or apoplast in plants. At the ER, these secreted proteins undergo multiple processing steps, which are supervised and conducted by the ER quality control system. Notably, processing of secreted proteins can considerably elevate under stress conditions and exceed ER folding capacities. The resulting accumulation of unfolded proteins is defined as ER stress. The efficiency of cells to re-establish proper ER function is crucial for stress adaptation. Besides delivering proteins directly antagonizing and resolving stress conditions, the ER monitors synthesis of immune receptors. This indicates the significance of the ER for the establishment and function of the plant immune system. Recent studies point out the fragility of the entire system and highlight the ER as initiator of programed cell death (PCD) in plants as was reported for vertebrates. This review summarizes current knowledge on the impact of the ER on immune and PCD signaling. Understanding the integration of stress signals by the ER bears a considerable potential to optimize development and to enhance stress resistance of plants.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription.

PubMed

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-03-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. © 2015 The Authors.

ER sheet persistence is coupled to myosin 1c-regulated dynamic actin filament arrays.

PubMed

Joensuu, Merja; Belevich, Ilya; Rämö, Olli; Nevzorov, Ilya; Vihinen, Helena; Puhka, Maija; Witkos, Tomasz M; Lowe, Martin; Vartiainen, Maria K; Jokitalo, Eija

2014-04-01

The endoplasmic reticulum (ER) comprises a dynamic three-dimensional (3D) network with diverse structural and functional domains. Proper ER operation requires an intricate balance within and between dynamics, morphology, and functions, but how these processes are coupled in cells has been unclear. Using live-cell imaging and 3D electron microscopy, we identify a specific subset of actin filaments localizing to polygons defined by ER sheets and tubules and describe a role for these actin arrays in ER sheet persistence and, thereby, in maintenance of the characteristic network architecture by showing that actin depolymerization leads to increased sheet fluctuation and transformations and results in small and less abundant sheet remnants and a defective ER network distribution. Furthermore, we identify myosin 1c localizing to the ER-associated actin filament arrays and reveal a novel role for myosin 1c in regulating these actin structures, as myosin 1c manipulations lead to loss of the actin filaments and to similar ER phenotype as observed after actin depolymerization. We propose that ER-associated actin filaments have a role in ER sheet persistence regulation and thus support the maintenance of sheets as a stationary subdomain of the dynamic ER network.

Sensitizing properties of luminescence centers on the emission of Er3+ in Si-rich SiO2 film

NASA Astrophysics Data System (ADS)

Fu, Qianyu; Gao, Yuhan; Li, Dongsheng; Yang, Deren

2016-05-01

In this paper, we report on the luminescence-center (LC)-mediated excitation of Er3+ as a function of annealing temperature in Er-doped Si-rich SiO2 (SRO) films fabricated by electron beam evaporation. It is found that the annealing temperature has significant effects on the emission of Er3+ and the specific optical-active point-defects called LCs within Er-doped SRO films. Different luminescence centers generated by the evolution of microstructures during annealing process act as efficient sensitizers for Er3+ in the films when the annealing temperature is below 1100 °C. Moreover, the temperature dependence of the energy coupling between LCs and Er3+ demonstrates the effective phonon-mediated energy transfer process. In addition, when the annealing temperature reaches 1100 °C, the decreased density of activable erbium ions induced by the aggregation of Er will bring detrimental effects on the emission of Er3+. It is demonstrated that an appropriate annealing process can be designed to achieve efficiently enhanced emissions from Er3+ ions by optimizing the density of LCs and the coupling between Er3+ and LCs.

Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

PubMed

Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

2018-05-01

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

Effect of chemical pressure on the crystal electric field states of erbium pyrochlore magnets

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

Gaudet, J; Hallas, A. A.; Kolesnikov, Alexander I.

We have carried out a systematic study of the crystal electric field excitations in the family of cubic pyrochlores Er 2B 2O 7 with B=Ge, Ti, Pt, and Sn, using neutron spectroscopy. All members of this family are magnetic insulators based on 4f 11Er 3+ and nonmagnetic B 4+. At sufficiently low temperatures, long-range antiferromagnetic order is observed in each of these Er 2B 2O 7 pyrochlores. The different ionic sizes associated with different nonmagnetic B 4+ cations correspond to positive or negative chemical pressure, depending on the relative contraction or expansion of the crystal lattice, which gives rise tomore » different local environments at the Er 3+ site. Our results show that the g-tensor components are XY-like for all four members of the Er 2B 2O 7 series. However, the XY anisotropy is much stronger for Er 2Pt 2O 7 and Er 2Sn 2O 7(g⊥/gz>25) than for Er 2Ge 2O 7 and Er 2Ti 2O 7(g⊥/gz<4). The variation in the nature of the XY anisotropy in these systems correlates strongly with their ground states as Er 2Ge 2O 7 and Er 2Ti 2O 7 order into Γ 5 magnetic structures, whereas Er 2Pt 2O 7 and Er 2Sn 2O 7 order in the Γ 7 Palmer-Chalker structure.« less

Effect of chemical pressure on the crystal electric field states of erbium pyrochlore magnets

NASA Astrophysics Data System (ADS)

Gaudet, J.; Hallas, A. M.; Kolesnikov, A. I.; Gaulin, B. D.

2018-01-01

We have carried out a systematic study of the crystal electric field excitations in the family of cubic pyrochlores Er2B2O7 with B =Ge , Ti, Pt, and Sn, using neutron spectroscopy. All members of this family are magnetic insulators based on 4 f11Er3 + and nonmagnetic B4 +. At sufficiently low temperatures, long-range antiferromagnetic order is observed in each of these Er2B2O7 pyrochlores. The different ionic sizes associated with different nonmagnetic B4 + cations correspond to positive or negative chemical pressure, depending on the relative contraction or expansion of the crystal lattice, which gives rise to different local environments at the Er3 + site. Our results show that the g -tensor components are X Y -like for all four members of the Er2B2O7 series. However, the X Y anisotropy is much stronger for Er2Pt2O7 and Er2Sn2O7(g⊥/gz>25 ) than for Er2Ge2O7 and Er2Ti2O7(g⊥/gz<4 ) . The variation in the nature of the X Y anisotropy in these systems correlates strongly with their ground states as Er2Ge2O7 and Er2Ti2O7 order into Γ5 magnetic structures, whereas Er2Pt2O7 and Er2Sn2O7 order in the Γ7 Palmer-Chalker structure.

Effect of chemical pressure on the crystal electric field states of erbium pyrochlore magnets

DOE PAGES

Gaudet, J; Hallas, A. A.; Kolesnikov, Alexander I.; ...

2018-01-17

We have carried out a systematic study of the crystal electric field excitations in the family of cubic pyrochlores Er 2B 2O 7 with B=Ge, Ti, Pt, and Sn, using neutron spectroscopy. All members of this family are magnetic insulators based on 4f 11Er 3+ and nonmagnetic B 4+. At sufficiently low temperatures, long-range antiferromagnetic order is observed in each of these Er 2B 2O 7 pyrochlores. The different ionic sizes associated with different nonmagnetic B 4+ cations correspond to positive or negative chemical pressure, depending on the relative contraction or expansion of the crystal lattice, which gives rise tomore » different local environments at the Er 3+ site. Our results show that the g-tensor components are XY-like for all four members of the Er 2B 2O 7 series. However, the XY anisotropy is much stronger for Er 2Pt 2O 7 and Er 2Sn 2O 7(g⊥/gz>25) than for Er 2Ge 2O 7 and Er 2Ti 2O 7(g⊥/gz<4). The variation in the nature of the XY anisotropy in these systems correlates strongly with their ground states as Er 2Ge 2O 7 and Er 2Ti 2O 7 order into Γ 5 magnetic structures, whereas Er 2Pt 2O 7 and Er 2Sn 2O 7 order in the Γ 7 Palmer-Chalker structure.« less

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology.

PubMed

Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

2017-04-08

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis.

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

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

Yang, Ping; Fu, Shilong; Cao, Zhifei

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressivemore » ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. • Oroxin B effectively exerts anti-lymphoma without obvious toxicity. • Oroxin B promotes tumor-suppressive DDIT3 and inhibits tumorigenic GRP78.« less

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

PubMed Central

Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

2017-01-01

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis. PMID:28397763

Quiescent deformation of the Aniakchak Caldera, Alaska mapped by InSAR

USGS Publications Warehouse

Kwoun, Oh-Ig; Lu, Zhong; Neal, Christina; Wicks, Charles W.

2006-01-01

The 10-km-wide caldera of the historically active Aniakchak volcano, Alaska, subsides ∼13 mm/yr, based on data from 19 European Remote Sensing Satellite (ERS-1 and ERS-2) interferometric synthetic aperture radar (InSAR) images from 1992 through 2002. The pattern of subsidence does not reflect the distribution of pyroclastic deposits from the last eruption in 1931 and therefore is not related to compaction of fragmental debris. Weighted least-squares inversion of the deformation maps indicates a relatively constant subsidence rate. Modeling the deformation with a Mogi point source locates the source of subsidence at ∼4 km below the central caldera floor, which is consistent with the inferred depth of magma storage before the 1931 eruption. Magmatic CO2 and He have been measured at a warm soda spring within the caldera, and several sub-boiling fumaroles persist elsewhere in the caldera. These observations suggest that recent subsidence can be explained by the cooling or degassing of a shallow magma body (∼4 km deep), and/or the reduction of the pore-fluid pressure of a cooling hydrothermal system. Ongoing deformation of the volcano detected by InSAR, in combination with magmatic gas output from at least one warm spring, and infrequent low-level bursts of seismicity below the caldera, indicate that the volcanic system is still active and requires close attention for the timely detection of possible hazards.

Influence of biocorrosion on microstructure and mechanical properties of deformed Mg-Y-Er-Zn biomaterial containing 18R-LPSO phase.

PubMed

Leng, Zhe; Zhang, Jinghuai; Yin, Tingting; Zhang, Li; Guo, Xuying; Peng, Qiuming; Zhang, Milin; Wu, Ruizhi

2013-12-01

The microstructure and mechanical properties of as-extruded Mg-8Y-1Er-2Zn (wt%) alloy containing long period stacking ordered (LPSO) phase are comparatively investigated before and after corrosion in a simulated body fluid (SBF) at 37°C. The as-extruded alloy consists of a long strip-like 18R-LPSO phase and some fine lamellae grains formed by primary recrystallization during the extrusion process. The hydrogen evolution volume per day fluctuates between 0.21 and 0.32ml/cm(2) in the immersion test for 240h, and the corresponding corrosion rate is calculated as 0.568mm/y. The corrosion product is determined as Mg(OH)2, whilst a Ca(H2PO4)2 compound is also observed on the surface of the samples. The corrosion site preferentially occurs at the interface between LPSO phase and Mg matrix. Before immersing, the tensile yield strength (TYS), ultimate tensile strength (UTS) and elongation of the alloy are 275MPa, 359MPa, and 19%, respectively. More attractively, these mechanical properties can be maintained even after immersing in SBF for 240h (TYS, UTS and elongation are 216MPa, 286MPa and 6.8%, respectively) because of the existence of high anti-corrosion LPSO phase. © 2013 Elsevier Ltd. All rights reserved.

Rare-earth elements in human colostrum milk.

PubMed

Poniedziałek, Barbara; Rzymski, Paweł; Pięt, Małgorzata; Niedzielski, Przemysław; Mleczek, Mirosław; Wilczak, Maciej; Rzymski, Piotr

2017-11-01

Rare-earth elements (REEs) are used in a growing number of applications, and their release to environment has increased over the decades. Knowledge of REEs in human milk and factors that could possibly influence their concentration is scarce. This study evaluated the concentrations of 16 REEs (Ce, Eu, Er, Gd, La, Nd, Pr, Sc, Sm, Dy, Ho, Lu, Tb, Tm, Y, and Yb) in human colostrum milk collected from Polish women (n = 100) with the ICP-OES technique. The concentrations (mean ± SD) of Pr (41.9 ± 13.2 μg L -1 ), Nd (11.0 ± 4.0 μg L -1 ), La (7.1 ± 5.2 μg L -1 ), and Er (2.2 ± 0.8 μg L -1 ) were found above detection limits. The total mean ± SD concentration of detected REEs was 60.9 ± 17.8 μg L -1 . Current smokers displayed significantly increased Nd concentrations compared to women who had never smoked. No other associations between REEs in colostrum milk and age, diet in pregnancy (food supplement use and frequency of fish, meat, and vegetable consumption) or place of living (urban/rural) were found. This study adds to general understanding of the occurrence and turnover of REEs in women and human fluids.

[Different patterns of follicular development and luteal function].

PubMed

Gu, L; Zhang, L; Gu, F

1995-09-01

To study the relationship between luteal function and different patterns of follicular development. Different patterns of follicular development as observed under transvaginal B-ultrasound in 85 infertile patients included: (1) Ovulation from normal follicle (ONF). (2) Ovulation from two follicles at the same cycle (O2F). (3) Ovulation from small follicle (OSF). (4) Ovulation from polycystic ovaries (PCO). (5) Luteinized unruptured follicle syndrome (LUFS). (6) Anovulation with follicular atresia. The luteal function of the first 5 types was evaluated by serum and peritoneal fluid estrogen, progesterone levels, endometrial histology, estradiol receptor (ER) and progesterone receptor (PR) analyaes, and the length of luteal phase. The incidence of luteal phase deficiency (LPD): short luteal phase was 10.42%, retardation of endometrial development was 4.17% in ONF, no LPD in O2F, 21.42% in OSF, 2/3 in PCO, 3/6 in LUFS, respectively. The incidence of LPD was 14.58% in ONF, 56.52% in abnormal follicular development groups (OSF, O2F and LUFS) (P < 0.005). It was found that the retardation of endometrial development was associated either with lowered serum P level or normal serum P but lowered ER and PR concentrations. The latter condition was recognized as "pseudocorpus luteum deficiency". The different patterns of follicular development may exert a great influence over luteal function through the different production of steroid hormones and their receptors.

Intermittency in the Helimak, a simple magnetic torus

NASA Astrophysics Data System (ADS)

Taylor, E. I.; Rowan, W. L.; Gentle, K. W.; Horton, W.; Bernard, T.

2017-10-01

Irregularly-spaced, large-amplitude bursts are observed in the Helimak plasma turbulence with sufficient definition to investigate their physical basis and possibly improve understanding of the induced particle transport. The Helimak is an experimental realization of a sheared cylindrical slab that generates and heats a plasma with microwaves and confines it in a helical magnetic field. Although it is MHD stable, the plasma is always in a nonlinearly saturated state of microturbulence. The intermittency in this turbulence manifests itself in highly skewed PDFs of the normalized electron density. Cross-conditional averaging exposes large amplitude structures propagating down the density gradient at a few hundred meters per second. Introduction of a radial electric field via bias plates appears to suppress these intermittent transport events (ITEs) for Er pointing down the density gradient. In addition, the cross-conditionally averaged waveforms are relatively unchanged as connection length is varied. Within certain regimes, our measurements are consistent with the predictions of a stochastic model that represents the plasma fluctuations as a random sequence of burst events. Furthermore, we attempt to gain insight into the physical origin of these ITEs by searching for similar statistical behavior in fluid and gyrokinetic simulations. This material is based upon work supported by the U.S. Department of Energy Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 04ER5476.

GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors.

PubMed

Yang, Yuqiong; Lu, Shanming; Zeng, Wenqin; Xie, Shoucheng; Xiao, Shengjun

2017-02-01

GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas, consistently showing that GATA3 was significantly more sensitive than traditional markers gross cystic disease fluid protein 15 (GCDFP15) and mammaglobin (MGB). However, clinically useful groups of breast carcinomas status were not identified, which were determining appropriate treatment strategy, affecting the prognosis. In this study, we undertook a comparative study of the marker GATA3 and GCDFP15 and MGB in clinically useful groups of paired primary and metastatic breast cancer. We retrieved 64 cases of matched primary and metastatic breast cancer from the surgical pathology archive at our institution. According to the emerging 2015 St. Gallen Consensus, the clinically useful groups were divided into ER and/or PR (+), HER2 (-), abbreviated as A; ER and/or PR (+), HER2 (+), abbreviated as B; ER and PR (-), HER2 (+), abbreviated as C; ER, PR and HER2 (-), abbreviated as D; each group contained 16 cases (n=16). Tissue microarrays were created, with three 1-mm punch specimens from each case. The tissue microarrays were cut at 4-μm thickness and stained with monoclonal antibodies to GATA3, GCDFP15, and MGB. Staining intensity (0-3+) and extent (0%-100%) were scored with an H-score calculated (range, 0-300). Sensitivities by varying H-score cutoffs (any; ≥50; ≥150) for a positive result in the clinically useful groups of matched primary or metastatic breast cancer among GATA3, GCDFP15, and MGB. GATA3 was significantly more sensitive than GCDFP15 and MGB A and B groups (P<.05) rather than C and D groups (P>.05). However, GATA3 in conjunction with GCDFP15 and MGB detection could improve the sensitivity of C group (P<.05) rather than D group (P>.05). Significantly, good coincidence was observed between primary and metastatic tumor GATA3 expression (κ value = 0.826 >0.75) as compared with the coincidence of GCDFP15 (κ value =0.492 <0.75) and MGB (κ value =0.593 <0.75) (both P<.05). In conclusion, GATA3 expression did not show the same sensitivity for the clinically useful groups of breast cancer. GATA3 expression is positively correlated with ER-positive, PR-positive, and HER2-positive carcinomas. In addition, the matched primary and metastatic tumor expression of GATA3 shows good coincidence. We propose the careful selection of GATA3 for identifying hormone receptor negativity of breast cancer, especially in the case of triple-negative breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

The SANT domain of human MI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription from its own promoter.

PubMed

Ding, Zhihu; Gillespie, Laura L; Mercer, F Corinne; Paterno, Gary D

2004-07-02

To gain insight into the regulation of hmi-er1 expression, we cloned a human genomic DNA fragment containing one of the two hmi-er1 promoters and consisting of 1460 bp upstream of the translation initiation codon of hMI-ER1. Computer-assisted sequence analysis revealed that the hmi-er1 promoter region contains a CpG island but lacks an identifiable TATA element, initiator sequence and downstream promoter element. This genomic DNA was able to direct transcription of a luciferase reporter gene in a variety of human cell lines, and the minimal promoter was shown to be located within-68/+144 bp. Several putative Sp1 binding sites were identified, and we show that Sp1 can bind to the hmi-er1 minimal promoter and increase transcription, suggesting that the level of hmi-er1 expression may depend on the availability of Sp1 protein. Functional analysis revealed that hMI-ER1 represses Sp1-activated transcription from the minimal promoter by a histone deacetylase-independent mechanism. Chromatin immunoprecipitation analysis demonstrated that both Sp1 and hMI-ER1 are associated with the chromatin of the hmi-er1 promoter and that overexpression of hMI-ER1 in cell lines that allow Tet-On-inducible expression resulted in loss of detectable Sp1 from the endogenous hmi-er1 promoter. The mechanism by which this occurs does not involve binding of hMI-ER1 to cis-acting elements. Instead, we show that hMI-ER1 physically associates with Sp1 and that endogenous complexes containing the two proteins could be detected in vivo. Furthermore, hMI-ER1 specifically interferes with binding of Sp1 to the hmi-er1 minimal promoter as well as to an Sp1 consensus oligonucleotide. Deletion analysis revealed that this interaction occurs through a region containing the SANT domain of hMI-ER1. Together, these data reveal a functional role for the SANT domain in the action of co-repressor regulatory factors and suggest that the association of hMI-ER1 with Sp1 represents a novel mechanism for the negative regulation of Sp1 target promoters.

Completion Report for Well ER-2-2 Corrective Action Unit 97: Yucca Flat/Climax Mine, Revision 1

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

Wurtz, Jeffrey

Well ER-2-2 was drilled for the U.S. Department of Energy, Nevada National Security Administration Nevada Field Office in support of the Underground Test Area (UGTA) Activity. The well was drilled from January 17 to February 8, 2016, as part of the Corrective Action Investigation Plan (CAIP) for Corrective Action Unit 97: Yucca Flat/Climax Mine, Nevada Test Site, Nevada. The primary purpose of the well was to collect hydrogeologic data to evaluate uncertainty in the flow and transport conceptual model and its contamination boundary forecasts, and to detect radionuclides in groundwater from the CALABASH (U2av) underground test. Well ER-2-2 was notmore » completed as planned due to borehole stability problems. As completed, the well includes a piezometer (p1) to 582 meters (m) (1,909 feet [ft]) below ground surface (bgs) installed in the Timber Mountain lower vitric-tuff aquifer (TMLVTA) and a 12.25-inch (in.) diameter open borehole to 836 m (2,743 ft) bgs in the Lower tuff confining unit (LTCU). A 13.375-in. diameter carbon-steel casing is installed from the surface to a depth of 607 m (1,990 ft) bgs. Data collected during borehole construction include composite drill cutting samples collected every 3.0 m (10 ft), geophysical logs to a depth of 672.4 m (2,206 ft) bgs, water-quality measurements (including tritium), water-level measurements, and slug test data. The well penetrated 384.05 m (1,260 ft) of Quaternary alluvium, 541.93 m (1,778 ft) of Tertiary Volcanics (Tv) rocks, and 127.71 m (419 ft) of Paleozoic carbonates. The stratigraphy and lithology were generally as expected. However, several of the stratigraphic units were significantly thicker then predicted—principally, the Tunnel formation (Tn), which had been predicted to be 30 m (100 ft) thick; the actual thickness of this unit was 268.22 m (880 ft). Fluid depths were measured in the borehole during drilling as follows: (1) in the piezometer (p1) at 552.15 m (1,811.53 ft) bgs and (2) in the main casing (m1) at 551.69 m (1,810.01 ft) bgs. As expected, field measurements for tritium were above the Safe Drinking Water Act limit (20,000 picocuries per liter) for a portion of the Tertiary volcanic section near the water table. Tritium concentrations were at or near the field detection limit in the Lower carbonate aquifer (LCA) while drilling. During drilling, a sample was collected while circulating in the LCA. The sample was submitted for off-site laboratory analysis. The sample results indicated low but measurable tritium concentrations. All Fluid Management Plan requirements were met during drilling activities.« less

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

Molina-Molina, Jose-Manuel; INSERM, U896, Montpellier, F-34298; Universite Montpellier1, Montpellier, F-34298

Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hER{alpha}), and there has been no comprehensive analysis of their potency in a system allowing comparison between hER{alpha} and hER{beta} activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fishmore » origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hER{alpha} and hER{beta} agonists (BP2 > THB > BP1) and displayed a stronger activation of hER{beta} compared with hER{alpha}, the opposite effect to that of estradiol (E{sub 2}). Unlike E{sub 2}, BPs were more active in rainbow trout ER{alpha} (rtER{alpha}) than in hER{alpha} assay. All four BP derivatives showed anti-androgenic activity (THB > BP2 > BP1 > BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ER{beta} versus ER{alpha} activation, support further investigation of their role as endocrine disrupters in humans and wildlife.« less

Orai3 channel is the 2-APB-induced endoplasmic reticulum calcium leak.

PubMed

Leon-Aparicio, Daniel; Pacheco, Jonathan; Chavez-Reyes, Jesus; Galindo, Jose M; Valdes, Jesus; Vaca, Luis; Guerrero-Hernandez, Agustin

2017-07-01

We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca 2+ leak using synthetic Ca 2+ indicators that report changes in both the cytoplasmic ([Ca 2+ ] i ) and the luminal ER ([Ca 2+ ] ER ) Ca 2+ concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca 2+ leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca 2+ ] ER but did not decrease the ER Ca 2+ leak after thapsigargin (TG). Orai3 channel, but neither Orai1 nor Orai2, colocalizes with expressed IP 3 R and only Orai3 channel supported the 2-APB-induced ER Ca 2+ leak, while Orai1 and Orai2 inhibited this type of ER Ca 2+ leak. Decreasing the expression of Orai3 inhibited the 2-APB-induced ER Ca 2+ leak but did not modify the ER Ca 2+ leak revealed by inhibition of SERCA pumps with TG. However, reducing the expression of Orai3 channel resulted in larger [Ca 2+ ] i response after TG but only when the ER store had been overloaded with Ca 2+ by eliminating the acidic internal Ca 2+ store with bafilomycin. These data suggest that Orai3 channel does not participate in the TG-revealed ER Ca 2+ leak but forms an ER Ca 2+ leak channel that is limiting the overloading with Ca 2+ of the ER store. Copyright © 2017 Elsevier Ltd. All rights reserved.

The risk of breast cancer associated with specific patterns of migraine history

PubMed Central

Lowry, Sarah J.; Malone, Kathleen E.; Cushing-Haugen, Kara L.; Li, Christopher I.

2014-01-01

Purpose Studies have suggested that a history of migraines may be associated with a lower risk of some types of breast cancer, though biological mechanisms are unclear. Identifying specific characteristics of migraines which are most strongly associated with breast cancer risk could improve our understanding of this relationship. Methods We ascertained specific characteristics of women's migraine histories (severity, timing features, presence of migraine aura). We used polytomous logistic regression to estimate the risk of ER+ ductal, ER- ductal, ER+ lobular, and ER+ ductal-lobular breast cancer associated with self-reported characteristics of migraine history. 715 breast cancer cases (276 ER+ ductal, 46 ER- ductal, 191 ER+ lobular, 202 ER+ ductal-lobular) and 376 controls ages 55-74 years were included in this population-based case-control study. Results Compared to women without a migraine history, women with a >30-year history of migraines had a 60% (95% CI: 0.2-0.6) lower risk of ER+ ductal breast cancer; those who had their first migraine before age 20 had 50% lower risks of ER+ ductal and ER+ lobular breast cancer (both 95%CIs: 0.3-0.9), and women who experienced migraine with aura had 30% (95%CI 0.5-0.98) and 40% (95%CI: 0.4-0.9) lower risks of ER+ ductal and ER+ lobular breast cancer, respectively. Conclusion The lower risk of ER+ breast cancer associated with migraine appears to be limited to those women with early onset or long duration of migraine history, or those who experienced migraine with aura. This expands our understanding of the relationship between migraine and breast cancer and provides additional insight into potential underlying biological mechanisms. PMID:25359301

Nodal endoplasmic reticulum, a specialized form of endoplasmic reticulum found in gravity-sensing root tip columella cells

NASA Technical Reports Server (NTRS)

Zheng, H. Q.; Staehelin, L. A.

2001-01-01

The endoplasmic reticulum (ER) of columella root cap cells has been postulated to play a role in gravity sensing. We have re-examined the ultrastructure of columella cells in tobacco (Nicotiana tabacum) root tips preserved by high-pressure freezing/freeze-substitution techniques to gain more precise information about the organization of the ER in such cells. The most notable findings are: the identification of a specialized form of ER, termed "nodal ER," which is found exclusively in columella cells; the demonstration that the bulk of the ER is organized in the form of a tubular network that is confined to a peripheral layer under the plasma membrane; and the discovery that this ER-rich peripheral region excludes Golgi stacks, vacuoles, and amyloplasts but not mitochondria. Nodal ER domains consist of an approximately 100-nm-diameter central rod composed of oblong subunits to which usually seven sheets of rough ER are attached along their margins. These domains form patches at the interface between the peripheral ER network and the ER-free central region of the cells, and they occupy defined positions within central and flanking columella cells. Over one-half of the nodal ER domains are located along the outer tangential walls of the flanking cells. Cytochalasin D and latrunculin A cause an increase in size and a decrease in numbers of nodal ER domains. We postulate that the nodal ER membranes locally modulate the gravisensing signals produced by the sedimenting amyloplasts, and that the confinement of all ER membranes to the cell periphery serves to enhance the sedimentability of the amyloplasts in the central region of columella cells.

Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells.

PubMed

Li, Yuehua; Jiang, Baohong; Wu, Xiaoping; Huang, Qin; Chen, Wenqi; Zhu, Hongbo; Qu, Xiaofei; Xie, Liming; Ma, Xin; Huang, Guo

2018-05-21

Estrogen drives the development and progression of estrogen receptor (ER)-positive breast cancer. However, the detailed mechanism underlying ER-driven carcinogenesis remains unclear despite extensive studies. Previously reports indicated higher expression of long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) in ER-positive breast cancer tissues than in ER-negative tissues. However, the functional relevance of MIAT in ER-positive breast cancer tumorigenesis was poorly understood. Here, we investigated the role of lncRNA MIAT in ER-positive breast cancer cells. MIAT was over-expressed in ER-positive breast cancer tissues and ER-positive breast cancer cell line MCF-7. Activating estrogen signaling by diethylstilbestrol (DES) led to a dose- and time-dependent up-regulation of MIAT in MCF-7 cells that was dependent on ERα, as evidenced by ERα silencing and pharmacological inhibition using ER antagonist ICI 182780. Silencing MIAT decreased DES-induced MCF-7 cell proliferation while overexpressing MIAT increased MCF-7 cell proliferation. Further mechanistic study identified that MIAT was critical for G1 to S phase cell cycle transition. Taken together, these results suggest that lncRNA MIAT is an estrogen-inducible lncRNA and a key regulator in ER-positive breast cancer cell growth. MIAT could serve as a potential biomarker and promising therapeutic target for ER-positive breast cancer. Copyright © 2018. Published by Elsevier Inc.

Naltrexone ER/Bupropion ER: A Review in Obesity Management.

PubMed

Greig, Sarah L; Keating, Gillian M

2015-07-01

Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(®), Mysimba(™)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of ≥ 30 kg/m(2) (i.e. obese) or a BMI of ≥ 27 kg/m(2) (i.e. overweight) in the presence of at least one bodyweight-related comorbidity, such as type 2 diabetes mellitus, hypertension or dyslipidaemia. In 56-week phase III trials in these patient populations, oral naltrexone ER/bupropion ER 32/360 mg/day was significantly more effective than placebo with regard to percentage bodyweight reductions from baseline and the proportion of patients who achieved bodyweight reductions of ≥ 5 and ≥ 10%. Significantly greater improvements in several cardiometabolic risk factors were also observed with naltrexone ER/bupropion ER versus placebo, as well as greater improvements in glycated haemoglobin levels in obese or overweight adults with type 2 diabetes. Naltrexone ER/bupropion ER was generally well tolerated in phase III trials, with nausea being the most common adverse event. Thus, naltrexone ER/bupropion ER 32/360 mg/day as an adjunct to a reduced-calorie diet and increased physical activity, is an effective and well tolerated option for chronic bodyweight management in obese adults or overweight adults with at least one bodyweight-related comorbidity.

Gene expression profiles of estrogen receptors α and β in the fetal bovine hypothalamus and immunohistochemical characterization during development.

PubMed

Panin, M; Corain, L; Montelli, S; Cozzi, B; Peruffo, A

2015-02-01

Steroid hormones intervene in the structural and functional regulation of neuronal processes during development and thus determine brain differentiation. The effects of estrogens are mediated by two transcription factors, namely estrogen receptor α (ER-α) and estrogen receptor β (ER-β), that regulate the expression of target genes through their binding to specific DNA target sequences. We describe the mRNA expression of ER-α and ER-β in the hypothalamus of developing male and female bovines as revealed by quantitative real-time polymerase chain reaction, and the distribution of the two ERs in hypothalamic sections of all fetal stages as shown by immunohistochemistry. The expression profiles of the mRNAs of both ERs are mutually correlated throughout the gestation period, and their levels increase significantly in the last stages of gestation. No sexual differences in the mRNA expression of either ER-α or ER-β have been found in our fetal specimens. The use of specific antisera against ER-α and ER-β has allowed us to characterize and confirm the distribution of these receptors in the hypothalami of all fetal stages considered. Our results offer detailed information concerning the distribution of ER-α and ER-β in the developing bovine hypothalamus and provide additional insights into the processes involved in the hypothalamic development of a mammal with a long gestation and a highly gyrencephalic brain.

Restoration of Tamoxifen Sensitivity in Estrogen Receptor–Negative Breast Cancer Cells: Tamoxifen-Bound Reactivated ER Recruits Distinctive Corepressor Complexes

PubMed Central

Sharma, Dipali; Saxena, Neeraj K.; Davidson, Nancy E.; Vertino, Paula M.

2010-01-01

Breast tumors expressing estrogen receptor-α (ER) respond well to therapeutic strategies using selective ER modulators, such as tamoxifen. However, ~ 30% of invasive breast cancers are hormone independent because they lack ER expression due to hypermethylation of ER promoter. Treatment of ER-negative breast cancer cells with demethylating agents [5-aza-2′-deoxycytidine (5-aza-dC)] and histone deacetylase (HDAC) inhibitors (trichostatin A) leads to expression of ER mRNA and functional protein. Here, we examined whether epigenetically reactivated ER is a target for tamoxifen therapy. Following treatment with trichostatin A and 5-aza-dC, the formerly unresponsive ER-negative MDA-MB-231 breast cancer cells became responsive to tamoxifen. Tamoxifen-mediated inhibition of cell growth in these cells is mediated at least in part by the tamoxifen-bound ER. Tamoxifen-bound reactivated ER induces transcriptional repression at estrogen-responsive genes by ordered recruitment of multiple distinct chromatin-modifying complexes. Using chromatin immunoprecipitation, we show recruitment of two different corepressor complexes to ER-responsive promoters in a mutually exclusive and sequential manner: the nuclear receptor corepressor-HDAC3 complex followed by nucleosome remodeling and histone deacetylation complex. The mechanistic insight provided by this study might help in designing therapeutic strategies directed toward epigenetic mechanisms in the prevention or treatment of breast cancer. PMID:16778215

A novel synonymous variant in the AVP gene associated with adFNDI causes partial RNA missplicing.

PubMed

Kvistgaard, Helene; Christensen, Jane H; Johansson, Jan-Ove; Gregersen, Niels; Rittig, Charlotte; Rittig, Soeren; Corydon, Thomas Juhl

2018-06-27

Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is characterized by severe polyuria and polydipsia and is caused by variations in the gene encoding the AVP prohormone. The study aimed to ascertain a correct diagnosis, to identify the underlying genetic cause of adFNDI in a Swedish kindred, and to test the hypothesis that the identified synonymous exonic variant in the AVP gene (c.324G>A), causes missplicing, and endoplasmic reticulum (ER) retention of the prohormone. Three affected family members were admitted for fluid deprivation test and dDAVP challenge test. Direct sequencing of the AVP gene was performed in affected subjects, and genotyping of the identified variant was performed in family members. The variant was examined by expression of AVP minigenes containing the entire coding regions as well as intron 2 of AVP. Clinical tests revealed significant phenotypical variation with both complete and partial adFNDI phenotype. DNA analysis revealed a synonymous c.324G>A substitution in one allele of the AVP gene in affected family members only. Cellular studies revealed both normally spliced and misspliced pre-mRNA in cells transfected with the AVP c.324G>A minigene. Confocal laser scanning microscopy showed collective localization of the variant prohormone to ER and vesicular structures at the tip of cellular processes. We have identified a synonymous variant affecting the second nucleotide of exon 3 in the AVP gene (c.324G>A) in a kindred in which adFNDI segregates. Notably, we showed that this variant causes partial missplicing of pre-mRNA resulting in accumulation of variant prohormone in ER. Our study suggests that even a small amount of aberrant mRNA might be sufficient to disturb cellular function resulting in adFNDI.
. ©2018S. Karger AG, Basel.

Polyelectrolyte Structure and Interactions in Model Cystic Fibrosis Sputum

NASA Astrophysics Data System (ADS)

Slimmer, Scott; Angelini, Thomas; Liang, Hongjun; Butler, John; Wong, Gerard C. L.

2002-03-01

Cystic fibrosis sputum is a complex fluid consisting of a number of components, including mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems were created to simulate CF sputum in vitro, in order to elucidate the contributions of the different components. Preliminary results will be presented. This work was supported by NSF DMR-0071761, DOE DEFG02-91ER45439, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

75 FR 79365 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 1 December 9...: ER07-1106-009; ER08-1255-003; ER08-1255-004; ER10- 566-001; ER10-566-002. Applicants: ArcLight Energy Marketing, LLC, Oak Creek Wind Power, LLC, Coso Geothermal Power Holdings, LLC. Description: Supplement to...

77 FR 43279 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... that the Commission received the following electric corporate filings: Docket Numbers: EC12-120-000... 203 of the Federal Power Act and Requests for Expedited Consideration and Confidential Treatment of... electric rate filings: Docket Numbers: ER10-2460-001; ER10-2461-001; ER12-682-002; ER10- 2463-001; ER11...

The Entangled ER-Mitochondrial axis as a potential therapeutic strategy in Neurodegeneration: A Tangled Duo Unchained

PubMed Central

Joshi, Amit U.; Kornfeld, Opher S.; Mochly-Rosen, Daria

2016-01-01

Endoplasmic reticulum (ER) and mitochondrial function have both been shown to be critical events in neurodegenerative diseases. The ER mediates protein folding, maturation, sorting as well acts as calcium storage. The unfolded protein response (UPR) is a stress response of the ER that is activated by the accumulation of misfolded proteins within the ER lumen. Although the molecular mechanisms underlying ER stress-induced apoptosis are not completely understood, increasing evidence suggests that ER and mitochondria cooperate to signal cell death. Similarly, calcium-mediated mitochondrial function and dynamics not only contribute to ATP generation and calcium buffering but are also a linchpin in mediating cell fate. Mitochondria and ER form structural and functional networks (mitochondria-associated ER membranes [MAMs]) essential to maintaining cellular homeostasis and determining cell fate under various pathophysiological conditions. Regulated Ca2+ transfer from the ER to the mitochondria is important in maintaining control of pro-survival/pro-death pathways. In this review, we summarize the latest therapeutic strategies that target these essential organelles in the context of neurodegenerative diseases. PMID:27212603

Golgi enzymes do not cycle through the endoplasmic reticulum during protein secretion or mitosis

PubMed Central

Villeneuve, Julien; Duran, Juan; Scarpa, Margherita; Bassaganyas, Laia; Van Galen, Josse; Malhotra, Vivek

2017-01-01

Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. This result has been taken to indicate that Golgi-resident enzymes cycle to the ER constitutively. We show that ST-FRB is trapped in the ER even without Ii-FKBP upon rapamycin addition. This is because ER-Golgi–cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi, and are transported together back to the ER by KDEL receptor–mediated retrograde transport. Moreover, depletion of KDEL receptor prevents trapping of ST-FRB in the ER by rapamycin. Thus ST-FRB cycles artificially by binding to FKBP domain–containing proteins. In addition, Golgi-specific O-linked glycosylation of a resident ER protein occurs only upon artificial fusion of Golgi membranes with ER. Together these findings support the consensus view that there is no appreciable mixing of Golgi-resident enzymes with ER under normal conditions. PMID:27807044

Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies.

PubMed

Rath, Eva; Haller, Dirk

2011-06-01

Multiple cellular stress responses have been implicated in chronic diseases such as obesity, diabetes, cardiovascular, and inflammatory bowel diseases. Even though phenotypically different, chronic diseases share cellular stress signaling pathways, in particular endoplasmic reticulum (ER) unfolded protein response (UPR). The purpose of the ER UPR is to restore ER homeostasis after challenges of the ER function. Among the triggers of ER UPR are changes in the redox status, elevated protein synthesis, accumulation of unfolded or misfolded proteins, energy deficiency and glucose deprivation, cholesterol depletion, and microbial signals. Numerous mouse models have been used to characterize the contribution of ER UPR to several pathologies, and ER UPR-associated signaling has also been demonstrated to be relevant in humans. Additionally, recent evidence suggests that the ER UPR is interrelated with metabolic and inflammatory pathways, autophagy, apoptosis, and mitochondrial stress signaling. Furthermore, microbial as well as nutrient sensing is integrated into the ER-associated signaling network. The data discussed in the present review highlight the interaction of ER UPR with inflammatory pathways, metabolic processes and mitochondrial function, and their interrelation in the context of chronic diseases.

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

PubMed

Darling, Nicola J; Balmanno, Kathryn; Cook, Simon J

2017-01-01

Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation.

PubMed

Verrier, C S; Roodi, N; Yee, C J; Bailey, L R; Jensen, R A; Bustin, M; Parl, F F

1997-07-01

The estrogen receptor (ER) belongs to a family of ligand-inducible nuclear receptors that exert their effects by binding to cis-acting DNA elements in the regulatory region of target genes. The detailed mechanisms by which ER interacts with the estrogen response element (ERE) and affects transcription still remain to be elucidated. To study the ER-ERE interaction and transcription initiation, we employed purified recombinant ER expressed in both the baculovirus-Sf9 and his-tagged bacterial systems. The effect of high-mobility group (HMG) protein HMG-1 and purified recombinant TATA-binding protein-associated factor TAF(II)30 on ER-ERE binding and transcription initiation were assessed by electrophoretic mobility shift assay and in vitro transcription from an ERE-containing template (pERE2LovTATA), respectively. We find that purified, recombinant ER fails to bind to ERE in spite of high ligand-binding activity and electrophoretic and immunological properties identical to ER in MCF-7 breast cancer cells. HMG-1 interacts with ER and promotes ER-ERE binding in a concentration- and time-dependent manner. The effectiveness of HMG-1 to stimulate ER-ERE binding in the electrophoretic mobility shift assay depends on the sequence flanking the ERE consensus as well as the position of the latter in the oligonucleotide. We find that TAF(II)30 has no effect on ER-ERE binding either alone or in combination with ER and HMG-1. Although HMG-1 promotes ER-ERE binding, it fails to stimulate transcription initiation either in the presence or absence of hormone. In contrast, TAF(II)30, while not affecting ER-ERE binding, stimulates transcription initiation 20-fold in the presence of HMG-1. These results indicate that HMG-1 and TAF(II)30 act in sequence, the former acting to promote ER-ERE binding followed by the latter to stimulate transcription initiation.

Impact of scavenging hydrogen peroxide in the endoplasmic reticulum for β cell function.

PubMed

Lortz, S; Lenzen, S; Mehmeti, I

2015-08-01

Oxidative folding of nascent proteins in the endoplasmic reticulum (ER), catalysed by one or more members of the protein disulfide isomerase family and the sulfhydryl oxidase ER oxidoreductin 1 (ERO1), is accompanied by generation of hydrogen peroxide (H2O2). Because of the high rate of insulin biosynthesis and the low expression of H2O2-inactivating enzymes in pancreatic β cells, it has been proposed that the luminal H2O2 concentration might be very high. As the role of this H2O2 in ER stress and proinsulin processing is still unsolved, an ER-targeted and luminal-active catalase variant, ER-Catalase N244, was expressed in insulin-secreting INS-1E cells. In these cells, the influence of ER-specific H2O2 removal on cytokine-mediated cytotoxicity and ER stress, insulin gene expression, insulin content and secretion was analysed. The expression of ER-Catalase N244 reduced the toxicity of exogenously added H2O2 significantly with a threefold increase of the EC50 value for H2O2. However, the expression of cytokine-induced ER stress genes and viability after incubation with β cell toxic cytokines (IL1β alone or together with TNFα+IFNγ) was not affected by ER-Catalase N244. In control and ER-Catalase N244 expressing cells, insulin secretion and proinsulin content was identical, while removal of luminal H2O2 reduced insulin gene expression and insulin content in ER-Catalase N244 expressing cells. These data show that ER-Catalase N244 reduced H2O2 toxicity but did not provide protection against pro-inflammatory cytokine-mediated toxicity and ER stress. Insulin secretion was not affected by decreasing H2O2 in the ER in spite of a reduced insulin transcription and processing. © 2015 Society for Endocrinology.

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress

PubMed Central

Kim, Min-Hyun; Aydemir, Tolunay B.; Kim, Jinhee; Cousins, Robert J.

2017-01-01

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet–induced ER stress using Zip14−/− (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders. PMID:28673968

Fruit and vegetable intake and risk of breast cancer by hormone receptor status.

PubMed

Jung, Seungyoun; Spiegelman, Donna; Baglietto, Laura; Bernstein, Leslie; Boggs, Deborah A; van den Brandt, Piet A; Buring, Julie E; Cerhan, James R; Gaudet, Mia M; Giles, Graham G; Goodman, Gary; Hakansson, Niclas; Hankinson, Susan E; Helzlsouer, Kathy; Horn-Ross, Pamela L; Inoue, Manami; Krogh, Vittorio; Lof, Marie; McCullough, Marjorie L; Miller, Anthony B; Neuhouser, Marian L; Palmer, Julie R; Park, Yikyung; Robien, Kim; Rohan, Thomas E; Scarmo, Stephanie; Schairer, Catherine; Schouten, Leo J; Shikany, James M; Sieri, Sabina; Tsugane, Schoichiro; Visvanathan, Kala; Weiderpass, Elisabete; Willett, Walter C; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zhang, Shumin M; Zhang, Xuehong; Ziegler, Regina G; Smith-Warner, Stephanie A

2013-02-06

Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer. Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided. Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04). We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.

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

Comparison of Estrogen Receptor Assay Results from Pathology Reports with Results from Central Laboratory Testing: Implications for Population-Based Studies of Breast Cancer

PubMed Central

Collins, LC; Marotti, J; Baer, HJ; Deitz, AC; Colditz, GA; Tamimi, RM

2014-01-01

Population-based studies of women with breast cancer commonly utilize information culled from pathology reports rather than central pathology review. The reliability of this information, particularly with regard to tumor biomarker results, is of concern. To address this, we evaluated the concordance between estrogen receptor (ER) results as determined from the original pathology reports and ER results obtained on the same specimens following testing in a single laboratory. Tissue microarrays (TMAs) were constructed from paraffin blocks of 3,167 breast cancers that developed in women enrolled in the Nurses’ Health Study. ER immunostains were performed on all TMA sections in single run. Results of ER immunostains performed on the TMA sections were compared with ER assay results abstracted from pathology reports. Among 1,851 cases of invasive breast cancer in which both ER results from pathology reports and central ER test results were available, the reported ER status and the ER status as determined from immunostains on TMAs were in agreement in 1,651 cases (87.3 %; kappa value 0.64, p<0.0001). When the comparison was restricted to ER assays originally performed by immunohistochemistry, the agreement rate increased to 92.3% (kappa value 0.78, p<0.0001). These results provide a framework for the accuracy of ER results abstracted from clinical records. Further, they suggest that utilizing ER assay results from pathology reports is a reasonable, albeit imperfect, alternative to central laboratory ER testing for large, population-based studies of patients with breast cancer. PMID:18230800

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

PubMed

Kim, Min-Hyun; Aydemir, Tolunay B; Kim, Jinhee; Cousins, Robert J

2017-07-18

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14 -/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.

The structure of the 168Er nucleus and the 166Er(t,p) 168 Er reaction in terms of the sdg interacting boson model

NASA Astrophysics Data System (ADS)

Akiyama, Y.; Heyde, K.; Arima, A.; Yoshinaga, N.

1986-05-01

Extending the interacting boson model by incorporating besides s and d, also the g-boson, we can describe the population of positive parity states of 168Er in the 166Er(t,P) 168Er reaction rather well. In particular, the excitation of I,Kπi = 4,3 +1; 2,2 +2; 0,0 +3 and 0,0 +4 states is much improved over the sd-IBM approach.

50 CFR Table 24 to Part 679 - Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic Trawl Fishing 24 Table 24 to Part 679... to Nonpelagic Trawl Fishing ER19FE08.009 ER19FE08.010 ER19FE08.011 ER19FE08.012 ER19FE08.013 ER19FE08...

50 CFR Table 24 to Part 679 - Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic Trawl Fishing 24 Table 24 to Part 679... to Nonpelagic Trawl Fishing ER19FE08.009 ER19FE08.010 ER19FE08.011 ER19FE08.012 ER19FE08.013 ER19FE08...

50 CFR Table 24 to Part 679 - Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Except as Noted, Locations in the Aleutian Islands Habitat Conservation Area Open to Nonpelagic Trawl Fishing 24 Table 24 to Part 679... to Nonpelagic Trawl Fishing ER19FE08.009 ER19FE08.010 ER19FE08.011 ER19FE08.012 ER19FE08.013 ER19FE08...

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

PubMed Central

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

Sensitizing properties of luminescence centers on the emission of Er{sup 3+} in Si-rich SiO{sub 2} film

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

Fu, Qianyu; Gao, Yuhan; Li, Dongsheng, E-mail: mselds@zju.edu.cn

2016-05-28

In this paper, we report on the luminescence-center (LC)-mediated excitation of Er{sup 3+} as a function of annealing temperature in Er-doped Si-rich SiO{sub 2} (SRO) films fabricated by electron beam evaporation. It is found that the annealing temperature has significant effects on the emission of Er{sup 3+} and the specific optical-active point-defects called LCs within Er-doped SRO films. Different luminescence centers generated by the evolution of microstructures during annealing process act as efficient sensitizers for Er{sup 3+} in the films when the annealing temperature is below 1100 °C. Moreover, the temperature dependence of the energy coupling between LCs and Er{sup 3+}more » demonstrates the effective phonon-mediated energy transfer process. In addition, when the annealing temperature reaches 1100 °C, the decreased density of activable erbium ions induced by the aggregation of Er will bring detrimental effects on the emission of Er{sup 3+}. It is demonstrated that an appropriate annealing process can be designed to achieve efficiently enhanced emissions from Er{sup 3+} ions by optimizing the density of LCs and the coupling between Er{sup 3+} and LCs.« less

Can functional emotion regulation protect children's mental health from war trauma? A Palestinian study.

PubMed

Diab, Marwan; Peltonen, Kirsi; Qouta, Samir R; Palosaari, Esa; Punamäki, Raija-Leena

2017-04-19

Effective emotion regulation (ER) is expected to protect mental health in traumatic stress. We first analysed the protective (moderator) function of different ER strategies and the associations between ER and mental health. Second, we tested gender differences in the protective function of ER and the associations between ER strategies and mental health. Participants were 482 Palestinian children (girls 49.4%; 10-13 years, M = 11.29, SD = .68) whose ER was assessed by the Emotion Regulation Questionnaire and mental health by post-traumatic stress (Children's Impact Event Scale), depressive, and psychological distress (Strengths and Difficulties Questionnaire) symptoms, and by psychosocial well-being (Mental Health Continuum-Short Form). War trauma involved 42 events. Results showed, first, that none of the ER strategies could protect a child's mental health from negative impact of war trauma, but self-focused ER was associated with low depressive symptoms, and other-facilitated ER with high psychological well-being. However, controlling of emotions formed a comprehensive risk for children's mental health. Second, gender differences were found in the protective role of ER, as self-focused and distractive ER formed a vulnerability among boys. The results are discussed in the context of emotional and regulative demands of war and life-threat. © 2017 International Union of Psychological Science.

ER/Golgi trafficking is facilitated by unbranched actin filaments containing Tpm4.2.

PubMed

Kee, Anthony J; Bryce, Nicole S; Yang, Lingyan; Polishchuk, Elena; Schevzov, Galina; Weigert, Roberto; Polishchuk, Roman; Gunning, Peter W; Hardeman, Edna C

2017-10-01

We have identified novel actin filaments defined by tropomyosin Tpm4.2 at the ER. EM analysis of mouse embryo fibroblasts (MEFs) isolated from mice expressing a mutant Tpm4.2 (Tpm4 Plt53/Plt53 ), incapable of incorporating into actin filaments, revealed swollen ER structures compared with wild-type (WT) MEFs (Tpm4 +/+ ). ER-to-Golgi, but not Golgi-to-ER trafficking was altered in the Tpm4 Plt53/Plt53 MEFs following the transfection of the temperature sensitive ER-associated ts045-VSVg construct. Exogenous Tpm4.2 was able to rescue the ER-to-Golgi trafficking defect in the Tpm4 Plt53/Plt53 cells. The treatment of WT MEFs with the myosin II inhibitor, blebbistatin, blocked the Tpm4.2-dependent ER-to-Golgi trafficking. The lack of an effect on ER-to-Golgi trafficking following treatment of MEFs with CK666 indicates that branched Arp2/3-containing actin filaments are not involved in anterograde vesicle trafficking. We propose that unbranched, Tpm4.2-containing filaments have an important role in maintaining ER/Golgi structure and that these structures, in conjunction with myosin II motors, mediate ER-to-Golgi trafficking. © 2017 Wiley Periodicals, Inc.

Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens

PubMed Central

Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

2016-01-01

The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat body and midgut. RNA interference (RNAi) of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster both suggested that the expression of CYP6ER1 is sufficient to confer imidacloprid resistance. Furthermore, we analyzed the interaction of imidacloprid and CYP6ER1 monooxygenase by using dynamic simulations and molecular docking. We found that Nitrogen atoms in the heterocycle of the imidacloprid molecule may bind to iron atoms in the center of the homology model of CYP6ER1 via 4,5-dihedro-1H-imidazole. This finding contributes to a better understanding of how CYP6ER1 takes part in the insecticide metabolism. PMID:27721443

Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens.

PubMed

Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

2016-10-10

The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat body and midgut. RNA interference (RNAi) of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster both suggested that the expression of CYP6ER1 is sufficient to confer imidacloprid resistance. Furthermore, we analyzed the interaction of imidacloprid and CYP6ER1 monooxygenase by using dynamic simulations and molecular docking. We found that Nitrogen atoms in the heterocycle of the imidacloprid molecule may bind to iron atoms in the center of the homology model of CYP6ER1 via 4,5-dihedro-1H-imidazole. This finding contributes to a better understanding of how CYP6ER1 takes part in the insecticide metabolism.

Prx1 and 3.2 kb Col1a1 promoters target distinct bone cell populations in transgenic mice

PubMed Central

Ouyang, Zhufeng; Chen, Zhijun; Ishikawa, Masakazu; Yue, Xiuzhen; Kawanami, Aya; Leahy, Patrick; Greenfield, Edward M.; Murakami, Shunichi

2014-01-01

Bones consist of a number of cell types including osteoblasts and their precursor cells at various stages of differentiation. To analyze cellular organization within the bone, we generated Col1a1CreER-DsRed transgenic mice that express, in osteoblasts, CreER and DsRed under the control of a mouse 3.2 kb Col1a1 promoter. We further crossed Col1a1CreER-DsRed mice with Prx1CreER-GFP mice that express CreER and GFP in osteochondro progenitor cells under the control of a 2.4 kb Prx1 promoter. Since the 3.2 kb Col1a1 promoter becomes active in osteoblasts at early stages of differentiation, and Prx1CreER-GFP-expressing periosteal cells show endogenous Col1a1 expression, we expected to find a cell population in which both the 2.4 kb Prx1 promoter and the 3.2 kb Col1a1 promoter are active. However, our histological and flow cytometric analyses demonstrated that these transgenes are expressed in distinct cell populations. In the periosteum of long bones, Col1a1CreER-DsRed is expressed in the innermost layer directly lining the bone surface, while Prx1CreER-GFP-expressing cells are localized immediately outside of the Col1a1CreER-DsRed-expressing osteoblasts. In the calvaria, Prx1CreER-GFP-expressing cells are also localized in the cranial suture mesenchyme. Our experiments further showed that Col1a1CreER-DsRed-expressing cells lack chondrogenic potential, while the Prx1CreER-GFP-expressing cells show both chondrogenic and osteogenic potential. Our results indicate that Col1a1CreER-DsRed-expressing cells are committed osteoblasts, while Prx1CreER-GFP-expressing cells are osteochondro progenitor cells. The Prx1CreER-GFP and Col1a1CreER-DsRed transgenes will offer novel approaches for analyzing lineage commitment and early stages of osteoblast differentiation under physiologic and pathologic conditions. PMID:24513582

Tamoxifen resistance and metastasis of human breast cancer cells were mediated by the membrane-associated estrogen receptor ER-α36 signaling in vitro.

PubMed

Gu, Wenwen; Dong, Nian; Wang, Peng; Shi, Changgen; Yang, Jun; Wang, Jian

2017-04-01

The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER + ) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER + breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium. The mechanism of TAM resistance in the ER + breast cancer cell line MCF-7 was investigated, and the results showed that the stimulating effect of insulin on susceptibility of MCF-7 to TAM was mediated by ER-α36 and that the expression level of ER-α36 in TAM-resistant MCF-7 cells was also significantly increased. Both TAM and estradiol (E2) could promote the migration of triple negative (ER-α66 - /PR - /HER2 - ) and ER-α36 + /GPER1 + breast cancer cells MDA-MB-231. The migration of MDA-MB-231 cells was inhibited by the down-regulated intracellular expression of ER-α36 by transient transfection of specific small interfering RNA, whereas no effect of GPER1 down-regulation was observed. Meanwhile, the effect of TAM on the migration of ER-α36-down-regulated MDA-MB-231 cells was also reduced. Furthermore, it was found that TAM enhanced the distribution of integrin β1 on the cell surface but did not affect the expression of integrin β1 in MDA-MB-231 cells. Collectively, these data suggested that ER-α36 signaling might play critical roles in acquired and de novo TAM resistance and metastasis of breast cancer, and ER-α36 might present a potential biomarker of TAM resistance in the clinical diagnosis and treatment of ER + breast cancer.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

PubMed

Valberg, S J; McKenzie, E C; Eyrich, L V; Shivers, J; Barnes, N E; Finno, C J

2016-09-01

Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Prospective and retrospective histopathological description. Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. © 2015 EVJ Ltd.

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer.

PubMed

Pinhel, Isabel; Hills, Margaret; Drury, Suzanne; Salter, Janine; Sumo, Georges; A'Hern, Roger; Bliss, Judith M; Sestak, Ivana; Cuzick, Jack; Barrett-Lee, Peter; Harris, Adrian; Dowsett, Mitch

2012-03-14

Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors. ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts. ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease. Clinical trial identifier: ISRCTN31514446.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis

PubMed Central

VALBERG, S. J.; McKENZIE, E. C.; EYRICH, L. V.; SHIVERS, J.; BARNES, N. E.; FINNO, C. J.

2016-01-01

Summary Reasons for performing study Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. Conclusions In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. PMID:26234161

76 FR 64341 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

....... Midwest Independent Transmission System Operator, Inc. E-12 ER10-1069-001 Southwest Power Pool, Inc. E-13 ER11-3627-000 Southwest Power Pool, Inc. E-14 ER11-4358-000 Southern California Edison Company. ER11..., Southwest Power Pool, Inc. ER11-121-000. E-20 EL11-54-000 Buckeye Power, Inc. v. American Transmission...

78 FR 59920 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric rate filings: Docket Numbers: ER10-2602-006; ER10-2604-003; ER10-2603-003; ER10- 2609-005; ER10-2606-005. Applicants: Escanaba Paper Company, Luke Paper Company, Rumford Paper Company, NewPage...

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

PubMed

Costello, Joseph L; Castro, Inês G; Hacker, Christian; Schrader, Tina A; Metz, Jeremy; Zeuschner, Dagmar; Azadi, Afsoon S; Godinho, Luis F; Costina, Victor; Findeisen, Peter; Manner, Andreas; Islinger, Markus; Schrader, Michael

2017-02-01

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A-binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering. © 2017 Costello et al.

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

PubMed Central

Costello, Joseph L.; Hacker, Christian; Schrader, Tina A.; Zeuschner, Dagmar; Findeisen, Peter

2017-01-01

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering. PMID:28108524

ER-plasma membrane junctions: Why and how do we study them?

PubMed

Chang, Chi-Lun; Chen, Yu-Ju; Liou, Jen

2017-09-01

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are membrane microdomains important for communication between the ER and the PM. ER-PM junctions were first reported in muscle cells in 1957, but mostly ignored in non-excitable cells due to their scarcity and lack of functional significance. In 2005, the discovery of stromal interaction molecule 1 (STIM1) mediating a universal Ca 2+ feedback mechanism at ER-PM junctions in mammalian cells led to a resurgence of research interests toward ER-PM junctions. In the past decade, several major advancements have been made in this emerging topic in cell biology, including the generation of tools for labeling ER-PM junctions and the unraveling of mechanisms underlying regulation and functions of ER-PM junctions. This review summarizes early studies, recently developed tools, and current advances in the characterization and understanding of ER-PM junctions. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017 Elsevier B.V. All rights reserved.

ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence

PubMed Central

Miyazaki, Taiga; Kohno, Shigeru

2014-01-01

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence. PMID:24335436

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

PubMed

Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew; Cornwell, MacIntosh; Liu, Weihan; Nardone, Agostina; Xiao, Tengfei; Li, Wei; Qiu, Xintao; Buchwalter, Gilles; Feiglin, Ariel; Abell-Hart, Kayley; Fei, Teng; Rao, Prakash; Long, Henry; Kwiatkowski, Nicholas; Zhang, Tinghu; Gray, Nathanael; Melchers, Diane; Houtman, Rene; Liu, X Shirley; Cohen, Ofir; Wagle, Nikhil; Winer, Eric P; Zhao, Jean; Brown, Myles

2018-02-12

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER + ) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Upconversion properties of Er3+/Yb3+ co-doped TeO2-TiO2-K2O glasses.

PubMed

Su, Fangning; Deng, Zaide

2006-01-01

The Er3+/Yb3+ co-doped TeO2-TiO2-K2O glasses were prepared by conventional melting procedures, and their upconversion spectra were performed. The dependence of luminescence intensity on the ratio of Yb3+/Er3+ was studied, and the relationship between green upconversion luminescence intensity and Er3+ concentration is discussed in detail. The 546 nm green upconversion luminescence intensity is optimised in the studied glasses either when the Yb3+/Er3+ ratio is 25/1 and Er3+ concentration is 0.1 mol%, or when the Yb3+/Er3+ ratio is 10/1 and Er3+ concentration is 0.15 mol%. These glasses could be one of the potential candidates for LD pumping microchip solid-state lasers.

ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

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

Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki

2011-02-18

Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. Themore » overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.« less

Simultaneous Fluorescence Visualization of Endoplasmic Reticulum Superoxide Anion and Polarity in Myocardial Cells and Tissue.

PubMed

Xiao, Haibin; Wu, Chuanchen; Li, Ping; Tang, Bo

2018-05-15

Diabetic cardiomyopathy (DCM) is a critical complication of diabetes, the accurate pathogenesis of which remains elusive. It is widely accepted that endoplasmic reticulum (ER) stress and abnormal fluctuations of reactive oxygen species (ROS) are considered to be closely associated with progress of DCM. In addition, DCM-induced changes of myocardial tissue and ROS-derived oxidation of proteins will cause changes of the hydrophilic and hydrophobic domains and may further seriously alter the myocardial cell polarity. Thus, real-time detection of ROS and polarity in ER of live cells and in tissue will contribute to revealing the exact molecular mechanisms of DCM. In this article, we first present an ER-targetable fluorogenic probe termed ER-NAPC for sensitive and selective detection of superoxide anion (O 2 •- ). ER-NAPC can precisely target ER and visualize the increase of O 2 •- level in a live H9c2 cardiomyocyte cell during ER stress. Meanwhile, by combining ER-NAPC with a polarity-sensitive probe, ER-P, we accomplish the simultaneous fluorescence visualization of O 2 •- and polarity in ER of live cells and diabetic myocardial tissue. The dual-color fluorescence imaging results indicate that the O 2 •- level and polarity will synergistically rise during ER stress in live cells and diabetic myocardial tissue. The proposed dual-color imaging strategy may offer a proven methodology for studying coordinated variation of different parameters during ER stress oriented disease.

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

Oh, Yohan; Chung, Kwang Chul, E-mail: kchung@yonsei.ac.kr

Highlights: Black-Right-Pointing-Pointer ZNF131 directly interacts with ER{alpha}. Black-Right-Pointing-Pointer The binding affinity of ZNF131 to ER{alpha} increases upon E2 stimulation. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-dimerization and E2-induced breast cancer cell proliferation. Black-Right-Pointing-Pointer ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor. -- Abstract: Steroid hormone estrogen elicits various physiological functions, many of which are mediated through two structurally and functionally distinct estrogen receptors, ER{alpha} and ER{beta}. The functional role of zinc finger protein 131 (ZNF131) is poorly understood, but it is assumed to possess transcriptional regulation activity due to the presence of amore » DNA binding motif. A few recent reports, including ours, revealed that ZNF131 acts as a negative regulator of ER{alpha} and that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling. However, its molecular mechanism for ER{alpha} inhibition has not been elucidated in detail. Here, we demonstrate that ZNF131 directly interacts with ER{alpha}, which consequently inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Moreover, we show that the C-terminal region of ZNF131 containing the SUMOylation site is necessary for its inhibition of estrogen signaling. Taken together, these data suggest that ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor.« less

Emotion Regulation and Depressive Symptoms: Close Relationships as Social Context and Influence

PubMed Central

Marroquín, Brett; Nolen-Hoeksema, Susan

2015-01-01

Depression is associated with social dysfunction and maladaptive social environments, but mechanisms through which social relationships affect depressive psychopathology are unclear. We hypothesized that emotion regulation (ER) is such a mechanism, with outcomes of individuals’ ER efforts sensitive to the social context, and individuals’ ER strategy repertoire and use sensitive to social influence. In Study 1, a longitudinal study of community adults (N = 1,319), associations of individuals’ ER strategies with depressive symptoms depended on social connectedness and romantic relationship status (social context hypothesis). Moreover, associations of social connectedness and relationship status with symptoms were accounted for by maladaptive ER concurrently and, for social connectedness, prospectively over 1 year (social influence hypothesis). Study 2a, using a national sample (N = 772), replicated and extended these findings with a broader array of ER strategies, and ruled out alternative explanations regarding social skills and psychological wellbeing. Among participants in romantic relationships (Study 2b; N = 558), intimacy and trust buffered associations of maladaptive ER strategies with symptoms (context), and maladaptive and adaptive ER mediated links between relationship variables and symptoms (influence). Findings suggest that close relationships—and variation in underlying relational processes within relationships— influence the ER strategies people use, and also affect whether individuals’ own ER repertoires contribute to depression when deployed. Results elucidate core social mechanisms of ER in terms of both basic processes and depressive psychopathology, suggest ER is a channel through which social factors affect internal functioning and mental health, and inform relationship pathways for clinical intervention. PMID:26479366

Untangling the web: Mechanisms underlying ER network formation

PubMed Central

Goyal, Uma; Blackstone, Craig

2013-01-01

The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

Immune-Specific Expression and Estrogenic Regulation of the Four Estrogen Receptor Isoforms in Female Rainbow Trout (Oncorhynchus mykiss).

PubMed

Casanova-Nakayama, Ayako; Wernicke von Siebenthal, Elena; Kropf, Christian; Oldenberg, Elisabeth; Segner, Helmut

2018-03-21

Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER) subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens. Consequently, the aims of the present study were (i) to determine the absolute mRNA copy numbers of the four ER isoforms in the immune organs and cells of rainbow trout, Oncorhynchus mykiss , and to compare them to the hepatic ER numbers; (ii) to analyse the ER mRNA isoform ratios in the immune system; and, (iii) finally, to examine the alterations of immune ER mRNA expression levels in sexually immature trout exposed to 17β-estradiol (E2), as well as the alterations of immune ER mRNA expression levels in sexually mature trout during the reproductive cycle. All four ER isoforms were present in immune organs-head kidney, spleen-and immune cells from head kidney and blood of rainbow trout, but their mRNA levels were substantially lower than in the liver. The ER isoform ratios were tissue- and cell-specific, both within the immune system, but also between the immune system and the liver. Short-term administration of E2 to juvenile female trout altered the ER mRNA levels in the liver, but the ERs of the immune organs and cells were not responsive. Changes of ER gene transcript numbers in immune organs and cells occurred during the reproductive cycle of mature female trout, but the changes in the immune ER profiles differed from those in the liver and gonads. The correlation between ER gene transcript numbers and serum E2 concentrations was only moderate to low. In conclusion, the low mRNA numbers of nuclear ER in the trout immune system, together with their limited estrogen-responsiveness, suggest that the known estrogen actions on trout immunity may be not primarily mediated through genomic actions, but may involve other mechanisms, such as non-genomic pathways or indirect effects.

Learning to See: Research in Training a Robot Vision System

DTIC Science & Technology

2008-12-01

Seraji (2001) and Howard et al. (2001) was focused...Threshold Fe at ur es P er S eg m en t 0.1 0.2 0.3 0.4 0.5 0 5 10 15 20 25 0.1 0.2 0.3 0.4 0.5 Trafficability Score Distance Threshold Fe at ur es P er...S eg m en t 5 10 15 20 25 Fe at ur es P er S eg m en t Fe at ur es P er S eg m en t Fe at ur es P er S eg m en t Fe at ur es P er S eg m en

75 FR 5779 - Notice Providing Agenda for Technical Conference on RTO/ISO Responsiveness

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

.... Southwest Power Pool, Inc Docket Nos. ER09-1050-000, ER09- 1192-000. ISO New England, Inc. and New England Docket No. ER09-1051-000. Power Pool. PJM Interconnection, LLC Docket No. ER09-1063-000. New York Independent System Operator, Docket No. ER09-1142-000. Inc. On November 13, 2009, the Commission issued a...

49 CFR Appendix A to Part 595 - Information Brochure

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Information Brochure A Appendix A to Part 595 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... to Part 595—Information Brochure ER21NO97.000 ER21NO97.001 ER21NO97.002 ER21NO97.003 ER21NO97.004...

78 FR 2382 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

.... Comments Due: 5 p.m. ET 3/1/13. Docket Numbers: ER10-2854-001. Applicants: ConocoPhillips Company.... Accession Number: 20121231-5130. Comments Due: 5 p.m. ET 1/22/13. Docket Numbers: ER11-3401-008. Applicants... Number: 20121231-5133. Comments Due: 5 p.m. ET 3/1/13. Docket Numbers: ER11-4683-003; ER11-4684-003; ER11...

49 CFR Appendix B to Part 230 - Diagrams and Drawings

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Diagrams and Drawings B Appendix B to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... to Part 230—Diagrams and Drawings ER17No99.015 ER17No99.016 ER17No99.017 ER17No99.018 ER17No99.019...

49 CFR Appendix A to Part 595 - Information Brochure

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Information Brochure A Appendix A to Part 595 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... to Part 595—Information Brochure ER21NO97.001 ER21NO97.002 ER21NO97.003 ER21NO97.004 ER21NO97.005...

77 FR 10505 - Notice of Attendance at PJM Interconnection, L.L.C. Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Interconnection, L.L.C. Meetings The Federal Energy Regulatory Commission (Commission) hereby gives notice that members of the Commission and Commission staff may attend upcoming PJM Interconnection, L.L.C. (PJM..., PJM Interconnection, L.L.C. Docket Nos. ER06-456, ER06-880, ER06-954, ER06-1271, EL07-57, ER07-424...

Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP.

PubMed

Henderson, Mark J; Wires, Emily S; Trychta, Kathleen A; Yan, Xiaokang; Harvey, Brandon K

2015-09-06

The endoplasmic reticulum (ER) contains the highest level of intracellular calcium, with concentrations approximately 5,000-fold greater than cytoplasmic levels. Tight control over ER calcium is imperative for protein folding, modification and trafficking. Perturbations to ER calcium can result in the activation of the unfolded protein response, a three-prong ER stress response mechanism, and contribute to pathogenesis in a variety of diseases. The ability to monitor ER calcium alterations during disease onset and progression is important in principle, yet challenging in practice. Currently available methods for monitoring ER calcium, such as calcium-dependent fluorescent dyes and proteins, have provided insight into ER calcium dynamics in cells, however these tools are not well suited for in vivo studies. Our lab has demonstrated that a modification to the carboxy-terminus of Gaussia luciferase confers secretion of the reporter in response to ER calcium depletion. The methods for using a luciferase based, secreted ER calcium monitoring protein (SERCaMP) for in vitro and in vivo applications are described herein. This video highlights hepatic injections, pharmacological manipulation of GLuc-SERCaMP, blood collection and processing, and assay parameters for longitudinal monitoring of ER calcium.

SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae

PubMed Central

Lee, Miriam; Ko, Young-Joon; Moon, Yeojin; Han, Minsoo; Kim, Hyung-Wook; Lee, Sung Haeng; Kang, KyeongJin

2015-01-01

Dynamin-like GTPases of the atlastin family are thought to mediate homotypic endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism remains largely unclear. Here, we developed a simple and quantitative in vitro assay using isolated yeast microsomes for measuring yeast atlastin Sey1p-dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE-mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p, another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on isolated microsomes, together with the lack of fusion between Sey1p proteoliposomes even with a 25-fold excess of the physiological concentration of Sey1p, suggests that Sey1p requires additional factors to support ER fusion in vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion is involved in atlastin-initiated homotypic ER fusion. PMID:26216899

Children with social anxiety and other anxiety disorders show similar deficits in habitual emotional regulation: evidence for a transdiagnostic phenomenon.

PubMed

Keil, Verena; Asbrand, Julia; Tuschen-Caffier, Brunna; Schmitz, Julian

2017-07-01

Deficits in emotion regulation (ER) are an important factor in maintaining social anxiety disorder (SAD) in adults. As SAD and ER problems typically develop during childhood and adolescence, and are maintained dynamically within the parent-child dyad, research on families can help to reveal the role ER plays in the early development of SAD. The current study assessed self-reported habitual ER in dyads of children with SAD (n = 31), children with mixed anxiety disorders (MAD; n = 41) and healthy control children (HC; n = 36), and their parents. Results indicate a transdiagnostic quality of ER in that, children with SAD and children with MAD similarly reported less adaptive and more maladaptive ER strategies than HC children, whereas no group differences in parental ER strategies emerged. Furthermore, children's ER strategies aggressive action, withdrawal and self-devaluation and the parental ER strategy reappraisal were associated with social anxiety symptoms. These results suggest that there may be deficits in ER which generalize across childhood anxiety disorders. Our results are discussed in relation to current theories and their implications for treatment of childhood SAD.

Rab32 modulates apoptosis onset and mitochondria-associated membrane (MAM) properties.

PubMed

Bui, Michael; Gilady, Susanna Y; Fitzsimmons, Ross E B; Benson, Matthew D; Lynes, Emily M; Gesson, Kevin; Alto, Neal M; Strack, Stefan; Scott, John D; Simmen, Thomas

2010-10-08

The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role in the onset of ER stress-mediated apoptosis, likely through the modulation of ER calcium signaling. These opposing roles of MAM-localized chaperones suggest the existence of mechanisms that regulate the composition and the properties of ER membrane domains. Our results now show that the GTPase Rab32 localizes to the ER and mitochondria, and we identify this protein as a regulator of MAM properties. Consistent with such a role, Rab32 modulates ER calcium handling and disrupts the specific enrichment of calnexin on the MAM, while not affecting the ER distribution of protein-disulfide isomerase and mitofusin-2. Furthermore, Rab32 determines the targeting of PKA to mitochondrial and ER membranes and through its overexpression or inactivation increases the phosphorylation of Bad and of Drp1. Through a combination of its functions as a PKA-anchoring protein and a regulator of MAM properties, the activity and expression level of Rab32 determine the speed of apoptosis onset.

Endoplasmic reticulum stress in kidney function and disease.

PubMed

Taniguchi, Mai; Yoshida, Hiderou

2015-07-01

Recently, a number of papers have reported that endoplasmic reticulum (ER) stress is involved in the onset of various kidney diseases, but the pathological mechanisms responsible have not been clarified. In this review, we summarize recent findings on this issue and try to clarify the pathology of ER stress-induced kidney diseases. ER stress is evoked in various kidney diseases, including diabetic nephropathy, renal fibrosis, inflammation or osmolar contrast-induced renal injury, ischemia-reperfusion, genetic mutations of renal proteins, proteinuria and cyclosporine A treatment. In some cases, chemical chaperones, such as 4-phenylbutyrate and taurodeoxycholic acid, relieve the symptoms, indicating that ER stress-induced apoptosis of renal cells is one of the major causes of certain kidney diseases. Actually, the ER stress response provides protection against some kidney diseases, although the PERK-ATF4-CHOP pathway of the ER stress response is proapoptotic in some kidney diseases. The disposal of unfolded proteins by autophagy is also protective for some ER stress-induced kidney diseases. Because ER stress is a major cause of some kidney diseases, the ER stress response and autophagy, which deal with unfolded proteins that accumulate in the ER, are promising therapeutic targets in acute and chronic kidney diseases.

Expanded polyglutamine embedded in the endoplasmic reticulum causes membrane distortion and coincides with Bax insertion

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

Ueda, Masashi; Li, Shimo; Itoh, Masanori

The endoplasmic reticulum (ER) is important in various cellular functions, such as secretary and membrane protein biosynthesis, lipid synthesis, and calcium storage. ER stress, including membrane distortion, is associated with many diseases such as Huntington's disease. In particular, nuclear envelope distortion is related to neuronal cell death associated with polyglutamine. However, the mechanism by which polyglutamine causes ER membrane distortion remains unclear. We used electron microscopy, fluorescence protease protection assay, and alkaline treatment to analyze the localization of polyglutamine in cells. We characterized polyglutamine embedded in the ER membrane and noted an effect on morphology, including the dilation of ERmore » luminal space and elongation of ER-mitochondria contact sites, in addition to the distortion of the nuclear envelope. The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. These results demonstrated that the ER membrane may be a target of polyglutamine, which triggers cell death through Bax. -- Highlights: •We characterized polyglutamine embedded in the ER membrane. •The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. •The ER membrane may be a target of polyglutamine, which triggers cell death.« less

Refractive index of erbium doped GaN thin films

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

Alajlouni, S.; Sun, Z. Y.; Li, J.

2014-08-25

GaN is an excellent host for erbium (Er) to provide optical emission in the technologically important as well as eye-safe 1540 nm wavelength window. Er doped GaN (GaN:Er) epilayers were synthesized on c-plane sapphire substrates using metal organic chemical vapor deposition. By employing a pulsed growth scheme, the crystalline quality of GaN:Er epilayers was significantly improved over those obtained by conventional growth method of continuous flow of reaction precursors. X-ray diffraction rocking curve linewidths of less than 300 arc sec were achieved for the GaN (0002) diffraction peak, which is comparable to the typical results of undoped high quality GaN epilayers andmore » represents a major improvement over previously reported results for GaN:Er. Spectroscopic ellipsometry was used to determine the refractive index of the GaN:Er epilayers in the 1540 nm wavelength window and a linear dependence on Er concentration was found. The observed refractive index increase with Er incorporation and the improved crystalline quality of the GaN:Er epilayers indicate that low loss GaN:Er optical waveguiding structures are feasible.« less

Identification of ER Proteins Involved in the Functional Organisation of the Early Secretory Pathway in Drosophila Cells by a Targeted RNAi Screen

PubMed Central

Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

2011-01-01

Background In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. Results To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for “more and smaller Golgi”) upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. Conclusions This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation. PMID:21383842

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

PubMed Central

Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

2014-01-01

Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

Correlation between oestrogen receptor protein expression in infiltrating ductal carcinoma of the breast by immunohistochemistry and cytosol measurements.

PubMed

Looi, L M; Yap, S F; Cheah, P L

1997-11-01

Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.

Myosin XI-dependent formation of tubular structures from endoplasmic reticulum isolated from tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-05-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER.

Myosin XI-Dependent Formation of Tubular Structures from Endoplasmic Reticulum Isolated from Tobacco Cultured BY-2 Cells1[W][OA

PubMed Central

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-01-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER. PMID:21427277

Identification of ER proteins involved in the functional organisation of the early secretory pathway in Drosophila cells by a targeted RNAi screen.

PubMed

Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

2011-02-23

In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for "more and smaller Golgi") upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation.

Early repolarization in Wolff-Parkinson-White syndrome: prevalence and clinical significance.

PubMed

Mizumaki, Koichi; Nishida, Kunihiro; Iwamoto, Jotaro; Nakatani, Yosuke; Yamaguchi, Yoshiaki; Sakamoto, Tamotsu; Tsuneda, Takayuki; Inoue, Hiroshi; Sakabe, Masao; Fujiki, Akira

2011-08-01

Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P < 0.005 and 42 ± 11 vs. 34 ± 9 ms, P < 0.001, respectively). In patients with WPW syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.

Erbium-based magnetic refrigerant (regenerator) for passive cryocooler

DOEpatents

Gschneidner, Jr., Karl A.; Pecharsky, Vitalij K.

1996-07-23

A two stage Gifford-McMahon cryocooler having a low temperature stage for reaching approximately 10K, wherein the low temperature stage includes a passive magnetic heat regenerator selected from the group consisting of Er.sub.6 Ni.sub.2 Sn, Er.sub.6 Ni.sub.2 Pb, Er.sub.6 Ni.sub.2 (Sn.sub.0.75 Ga.sub.0.25), and Er.sub.9 Ni.sub.3 Sn comprising a mixture of Er.sub.3 Ni and Er.sub.6 Ni.sub.2 Sn in the microstructure.

Erbium-based magnetic refrigerant (regenerator) for passive cryocooler

DOEpatents

Gschneidner, K.A. Jr.; Pecharsky, V.K.

1996-07-23

A two stage Gifford-McMahon cryocooler is disclosed having a low temperature stage for reaching approximately 10K, wherein the low temperature stage includes a passive magnetic heat regenerator selected from the group consisting of Er{sub 6}Ni{sub 2}Sn, Er{sub 6}Ni{sub 2}Pb, Er{sub 6}Ni{sub 2}(Sn{sub 0.75}Ga{sub 0.25}), and Er{sub 9}Ni{sub 3}Sn comprising a mixture of Er{sub 3}Ni and Er{sub 6}Ni{sub 2}Sn in the microstructure. 14 figs.

Novel condensation of Au-centered trigonal prisms in rare-earth-metal-rich tellurides: Er7Au2Te2 and Lu7Au2Te2.

PubMed

Gupta, Shalabh; Corbett, John D

2010-07-14

A new monoclinic structure occurs for Er(7)Au(2)Te(2) according to X-ray diffraction analysis of single crystals grown at 1200 degrees C: C2/m, Z = 4, a = 17.8310(9) A, b = 3.9819(5) A, c = 16.9089(9) A, beta = 104.361(4) degrees. The isostructural Lu(7)Au(2)Te(2) also exists according to X-ray powder pattern means, a = 17.536(4) A, b = 3.9719(4) A, c = 16.695(2) A, beta = 104.33(1) degrees. The structure contains zigzag chains of condensed, Au-centered tricapped trigonal prisms (TCTP) of Er along c that also share basal faces along b to generate puckered sheets. Further bi-face-capping Er atoms between these generate the three dimensional network along a, with tellurium in cavities outlined by augmented trigonal prismatic Er polyhedra. Bonding analysis via LMTO-DFT methods reveal very significant Er-Au bonding interactions, as quantified by their energy-weighted Hamilton overlap populations (-ICOHP), approximately 49% of the total for all interactions. These and similar Er-Te contributions sharply contrast with the small Er-Er population, only approximately 14% of the total in spite of the high proportion of Er-Er contacts. The strong polar bonding of Er to the electronegative Au and Te leaves Er relatively oxidized, with many of its 5d states falling above the Fermi level and empty. The contradiction with customary representations of structures that highlight rare-earth metal clusters is manifest. The large Er-Au Hamilton overlap population is in accord with the strong bonding between early and late transition metals first noted by Brewer in 1973. The relationship of this structure to the more distorted orthorhombic (Imm2) structure type of neighboring Dy(7)Ir(2)Te(2) is considered.

Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.

PubMed

Kanaya, Noriko; Somlo, George; Wu, Jun; Frankel, Paul; Kai, Masaya; Liu, Xueli; Wu, Shang Victoria; Nguyen, Duc; Chan, Nymph; Hsieh, Meng-Yin; Kirschenbaum, Michele; Kruper, Laura; Vito, Courtney; Badie, Behnam; Yim, John H; Yuan, Yuan; Hurria, Arti; Peiguo, Chu; Mortimer, Joanne; Chen, Shiuan

2017-06-01

The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy

PubMed Central

Giuliano, Mario; Hu, Huizhong; Wang, Yen-Chao; Fu, Xiaoyong; Nardone, Agostina; Herrera, Sabrina; Mao, Sufeng; Contreras, Alejandro; Gutierrez, Carolina; Wang, Tao; Hilsenbeck, Susan G.; De Angelis, Carmine; Wang, Nicholas J.; Heiser, Laura M.; Gray, Joe W.; Lopez-Tarruella, Sara; Pavlick, Anne C.; Trivedi, Meghana V.; Chamness, Gary C.; Chang, Jenny C.; Osborne, C. Kent; Rimawi, Mothaffar F.; Schiff, Rachel

2015-01-01

Purpose To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies, and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 post treatment), were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and western blot. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro. Results Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy, compared with untreated tumors, in both preclinical models (UACC812: ER p=0.0014; Bcl2 p<0.001. MCF7/HER2-18: ER p=0.0007; Bcl2 p=0.0306). In the neoadjuvant clinical study, lapatinib treatment for two weeks was associated with parallel upregulation of ER and Bcl2 (Spearman’s coefficient: 0.70; p=0.0002). Importantly, 18% of tumors originally ER-negative (ER−) converted to ER+ upon anti-HER2 therapy. In ER−/HER2+ MCF7/HER2-18 xenografts, ER re-expression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression (p=0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti-HER2-resistant growth (p<0.0001). Conclusion HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. PMID:26015514

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

PubMed Central

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value. PMID:25219910

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

PubMed

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.

PubMed

van Vilsteren, Frederike G I; Pouw, Roos E; Seewald, Stefan; Alvarez Herrero, Lorenza; Sondermeijer, Carine M T; Visser, Mike; Ten Kate, Fiebo J W; Yu Kim Teng, Karl C; Soehendra, Nib; Rösch, Thomas; Weusten, Bas L A M; Bergman, Jacques J G H M

2011-06-01

After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Genomic organization of the human mi-er1 gene and characterization of alternatively spliced isoforms: regulated use of a facultative intron determines subcellular localization.

PubMed

Paterno, Gary D; Ding, Zhihu; Lew, Yuan-Y; Nash, Gord W; Mercer, F Corinne; Gillespie, Laura L

2002-07-24

mi-er1 (previously called er1) is a fibroblast growth factor-inducible early response gene activated during mesoderm induction in Xenopus embryos and encoding a nuclear protein that functions as a transcriptional activator. The human orthologue of mi-er1 was shown to be upregulated in breast carcinoma cell lines and breast tumours when compared to normal breast cells. In this report, we investigate the structure of the human mi-er1 (hmi-er1) gene and characterize the alternatively spliced transcripts and protein isoforms. hmi-er1 is a single copy gene located at 1p31.2 and spanning 63 kb. It contains 17 exons and includes one skipped exon, a facultative intron and three polyadenylation signals to produce 12 transcripts encoding six distinct proteins. hmi-er1 transcripts were expressed at very low levels in most human adult tissues and the mRNA isoform pattern varied with the tissue. The 12 transcripts encode proteins containing a common internal sequence with variable N- and C-termini. Three distinct N- and two distinct C-termini were identified, giving rise to six protein isoforms. The two C-termini differ significantly in size and sequence and arise from alternate use of a facultative intron to produce hMI-ER1alpha and hMI-ER1beta. In all tissues except testis, transcripts encoding the beta isoform were predominant. hMI-ER1alpha lacks the predicted nuclear localization signal and transfection assays revealed that, unlike hMI-ER1beta, it is not a nuclear protein, but remains in the cytoplasm. Our results demonstrate that alternate use of a facultative intron regulates the subcellular localization of hMI-ER1 proteins and this may have important implications for hMI-ER1 function.

Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

PubMed Central

Xu, Jiqian; Hu, Houxiang; Chen, Bin; Yue, Rongchuan; Zhou, Zhou; Liu, Yin; Zhang, Shuang; Xu, Lei; Wang, Huan; Yu, Zhengping

2015-01-01

Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes. PMID:26291709

A Cluster of Exertional Rhabdomyolysis Cases in a ROTC Program Engaged in an Extreme Exercise Program.

PubMed

Raleigh, Meghan F; Barrett, John P; Jones, Brent D; Beutler, Anthony I; Deuster, Patricia A; O'Connor, Francis G

2018-03-01

Exertional rhabdomyolysis (ER) is on the rise among service members and high school and college athletes. Reported risk factors for ER include fitness level, sudden increase in exercise intensity and duration, and eccentric predominant exercise. This study examined an ER cluster among Reserve Officer Training Corps cadets who participated in a mandatory, timed, extreme conditioning program (ECP) workout. Forty-four cadets participated in this ECP; 11 were subsequently hospitalized with ER. Thirty-five cadets, including all who developed ER, completed a questionnaire to assess ECP times, prior fitness scores, and other ER risk factors. Cadets completed the ECP workout as individuals or in teams. Nine of 29 (31%) individual and two of 15 (13%) team participants were hospitalized with ER. Among the cadets, no associations were noted between hospitalization for ER and finish time, previous fitness scores, or dietary supplement use. The relative risk of developing ER was significantly increased in those who consumed alcohol in the week preceding the ECP (RR = 4.20; 95% CI 1.95, 9.03). In this cohort of Reserve Officer Training Corps cadets, an ECP resulted in a high rate of hospitalization for ER. Contrary to reported ER risk factors, higher baseline fitness was not protective. Rather, cadet knowledge that ECP performance was strongly linked to final cadet ranking greatly influenced intensity of effort.

Sensitivity and specificity of automated detection of early repolarization in standard 12-lead electrocardiography.

PubMed

Kenttä, Tuomas; Porthan, Kimmo; Tikkanen, Jani T; Väänänen, Heikki; Oikarinen, Lasse; Viitasalo, Matti; Karanko, Hannu; Laaksonen, Maarit; Huikuri, Heikki V

2015-07-01

Early repolarization (ER) is defined as an elevation of the QRS-ST junction in at least two inferior or lateral leads of the standard 12-lead electrocardiogram (ECG). Our purpose was to create an algorithm for the automated detection and classification of ER. A total of 6,047 electrocardiograms were manually graded for ER by two experienced readers. The automated detection of ER was based on quantification of the characteristic slurring or notching in ER-positive leads. The ER detection algorithm was tested and its results were compared with manual grading, which served as the reference. Readers graded 183 ECGs (3.0%) as ER positive, of which the algorithm detected 176 recordings, resulting in sensitivity of 96.2%. Of the 5,864 ER-negative recordings, the algorithm classified 5,281 as negative, resulting in 90.1% specificity. Positive and negative predictive values for the algorithm were 23.2% and 99.9%, respectively, and its accuracy was 90.2%. Inferior ER was correctly detected in 84.6% and lateral ER in 98.6% of the cases. As the automatic algorithm has high sensitivity, it could be used as a prescreening tool for ER; only the electrocardiograms graded positive by the algorithm would be reviewed manually. This would reduce the need for manual labor by 90%. © 2014 Wiley Periodicals, Inc.

The Cucumber leaf spot virus p25 auxiliary replicase protein binds and modifies the endoplasmic reticulum via N-terminal transmembrane domains

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

Ghoshal, Kankana; Theilmann, Jane; Reade, Ron

2014-11-15

Cucumber leaf spot virus (CLSV) is a member of the Aureusvirus genus, family Tombusviridae. The auxiliary replicase of Tombusvirids has been found to localize to endoplasmic reticulum (ER), peroxisomes or mitochondria; however, localization of the auxiliary replicase of aureusviruses has not been determined. We have found that the auxiliary replicase of CLSV (p25) fused to GFP colocalizes with ER and that three predicted transmembrane domains (TMDs) at the N-terminus of p25 are sufficient for targeting, although the second and third TMDs play the most prominent roles. Confocal analysis of CLSV infected 16C plants shows that the ER becomes modified includingmore » the formation of punctae at connections between ER tubules and in association with the nucleus. Ultrastructural analysis shows that the cytoplasm contains numerous vesicles which are also found between the perinuclear ER and nuclear membrane. It is proposed that these vesicles correspond to modified ER used as sites for CLSV replication. - Highlights: • The CLSV p25 auxiliary replicase targets the endoplasmic reticulum (ER). • Targeting of CLSV p25 is associated with ER restructuring. • Restructuring of the ER occurs during CLSV infection. • CLSV p25 contains 3 predicted transmembrane domains 2 of which are required for ER targeting. • Vesicles derived from the ER may be sites of CLSV replication.« less

The reticulons: Guardians of the structure and function of the endoplasmic reticulum

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

Di Sano, Federica; Bernardoni, Paolo; Piacentini, Mauro, E-mail: mauro.piacentini@uniroma2.it

2012-07-01

The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by a specific class of curvature stabilizing proteins, the reticulons and DP1; however it is still unclear how the sheets are assembled. The ER is the cellular compartment responsible for secretory and membrane protein synthesis. The reducing conditions of ER lead to the intra/inter-chain formation of new disulphide bonds into polypeptides during protein folding assessed by enzymatic or spontaneous reactions. Moreover, ER represents the main intracellular calcium storage site and it plays an important role in calcium signalingmore » that impacts many cellular processes. Accordingly, the maintenance of ER function represents an essential condition for the cell, and ER morphology constitutes an important prerogative of it. Furthermore, it is well known that ER undergoes prominent shape transitions during events such as cell division and differentiation. Thus, maintaining the correct ER structure is an essential feature for cellular physiology. Now, it is known that proper ER-associated proteins play a fundamental role in ER tubules formation. Among these ER-shaping proteins are the reticulons (RTN), which are acquiring a relevant position. In fact, beyond the structural role of reticulons, in very recent years new and deeper functional implications of these proteins are emerging in relation to their involvement in several cellular processes.« less

CHIP, a carboxy terminus HSP-70 interacting protein, prevents cell death induced by endoplasmic reticulum stress in the central nervous system.

PubMed

Cabral Miranda, Felipe; Adão-Novaes, Juliana; Hauswirth, William W; Linden, Rafael; Petrs-Silva, Hilda; Chiarini, Luciana B

2014-01-01

Endoplasmic reticulum (ER) stress and protein misfolding are associated with various neurodegenerative diseases. ER stress activates unfolded protein response (UPR), an adaptative response. However, severe ER stress can induce cell death. Here we show that the E3 ubiquitin ligase and co-chaperone Carboxyl Terminus HSP70/90 Interacting Protein (CHIP) prevents neuron death in the hippocampus induced by severe ER stress. Organotypic hippocampal slice cultures (OHSCs) were exposed to Tunicamycin, a pharmacological ER stress inducer, to trigger cell death. Overexpression of CHIP was achieved with a recombinant adeno-associated viral vector (rAAV) and significantly diminished ER stress-induced cell death, as shown by analysis of propidium iodide (PI) uptake, condensed chromatin, TUNEL and cleaved caspase 3 in the CA1 region of OHSCs. In addition, overexpression of CHIP prevented upregulation of both CHOP and p53 both pro-apoptotic pathways induced by ER stress. We also detected an attenuation of eIF2a phosphorylation promoted by ER stress. However, CHIP did not prevent upregulation of BiP/GRP78 induced by UPR. These data indicate that overexpression of CHIP attenuates ER-stress death response while maintain ER stress adaptative response in the central nervous system. These results indicate a neuroprotective role for CHIP upon UPR signaling. CHIP emerge as a candidate for clinical intervention in neurodegenerative diseases associated with ER stress.

Development of estrogen receptor beta binding prediction model using large sets of chemicals.

PubMed

Sakkiah, Sugunadevi; Selvaraj, Chandrabose; Gong, Ping; Zhang, Chaoyang; Tong, Weida; Hong, Huixiao

2017-11-03

We developed an ER β binding prediction model to facilitate identification of chemicals specifically bind ER β or ER α together with our previously developed ER α binding model. Decision Forest was used to train ER β binding prediction model based on a large set of compounds obtained from EADB. Model performance was estimated through 1000 iterations of 5-fold cross validations. Prediction confidence was analyzed using predictions from the cross validations. Informative chemical features for ER β binding were identified through analysis of the frequency data of chemical descriptors used in the models in the 5-fold cross validations. 1000 permutations were conducted to assess the chance correlation. The average accuracy of 5-fold cross validations was 93.14% with a standard deviation of 0.64%. Prediction confidence analysis indicated that the higher the prediction confidence the more accurate the predictions. Permutation testing results revealed that the prediction model is unlikely generated by chance. Eighteen informative descriptors were identified to be important to ER β binding prediction. Application of the prediction model to the data from ToxCast project yielded very high sensitivity of 90-92%. Our results demonstrated ER β binding of chemicals could be accurately predicted using the developed model. Coupling with our previously developed ER α prediction model, this model could be expected to facilitate drug development through identification of chemicals that specifically bind ER β or ER α .

75 FR 27772 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

...-003 Operator, Inc. E-12 ER09-1064-003, ER09-1064-004 California Independent System Operator Corporation. E-13 ER09-1064-001 California Independent System Operator Corporation. E-14 ER05-1410-015, EL05...

Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology

PubMed Central

Pawar, Sumit; Ungricht, Rosemarie; Tiefenboeck, Peter; Leroux, Jean-Christophe

2017-01-01

Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER. PMID:28826471

YAG:Er3+, CaF2:Er3+, and Er2O3 Emission Spectra Under Laser and Laser Thermal Excitation

NASA Astrophysics Data System (ADS)

Marchenko, V. M.

2018-05-01

Experimental luminescence and selective-emission (SE) spectra of YAG:Er3+ (10 at.%) and CaF2:Er3+ (1 at.%) single crystals and Er2O3 polycrystal under laser and laser thermal excitation of the Er3+-ion multiplets are compared. Luminescence spectra under resonant excitation are determined by multiplet population relaxation with the corresponding radiative and nonradiative probabilities. The form of the SE spectra is determined by the thermal population of the multiplets and the probabilities of only radiative transitions. The SE band at 800 nm (4I9/2 → 4I15/2) is an indicator of high-temperature thermal emission of Er3+ ions. The absence of this band in luminescence spectra is explained by the short lifetime of the τ(4I9/2) level of 53 ns at T = 300 K.

ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly.

PubMed

Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios

2016-03-07

The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Semi-active control of tracked vehicle suspension incorporating magnetorheological dampers

NASA Astrophysics Data System (ADS)

Ata, W. G.; Salem, A. M.

2017-05-01

In past years, the application of magnetorheological (MR) and electrorheological dampers in vehicle suspension has been widely studied, mainly for the purpose of vibration control. This paper presents theoretical study to identify an appropriate semi-active control method for MR-tracked vehicle suspension. Three representative control algorithms are simulated including the skyhook, hybrid and fuzzy-hybrid controllers. A seven degrees-of-freedom tracked vehicle suspension model incorporating MR dampers has been adopted for comparison between the performance of the three controllers. The model differential equations are derived based on Newton's second law of motion and the proposed control methods are developed. The performance of each control method under bump and sinusoidal road profiles for different vehicle speeds is simulated and compared with the performance of the conventional suspension system in time and frequency domains. The results show that the performance of tracked vehicle suspension with MR dampers is substantially improved. Moreover, the fuzzy-hybrid controller offers an excellent integrated performance in reducing the body accelerations as well as wheel bounce responses compared with the classical skyhook and hybrid controllers.

Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

PubMed

Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

2017-05-01

Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect renal cells against ER stress and ER stress-induced cell death, and would ultimately prevent the development of chronic kidney disease.

Small-Molecule “BRCA1-Mimetics” Are Antagonists of Estrogen Receptor-α

PubMed Central

Ma, Yongxian; Tomita, York; Preet, Anju; Clarke, Robert; Englund, Erikah; Grindrod, Scott; Nathan, Shyam; De Oliveira, Eliseu; Brown, Milton L.

2014-01-01

Context: Resistance to conventional antiestrogens is a major cause of treatment failure and, ultimately, death in breast cancer. Objective: The objective of the study was to identify small-molecule estrogen receptor (ER)-α antagonists that work differently from tamoxifen and other selective estrogen receptor modulators. Design: Based on in silico screening of a pharmacophore database using a computed model of the BRCA1-ER-α complex (with ER-α liganded to 17β-estradiol), we identified a candidate group of small-molecule compounds predicted to bind to a BRCA1-binding interface separate from the ligand-binding pocket and the coactivator binding site of ER-α. Among 40 candidate compounds, six inhibited estradiol-stimulated ER-α activity by at least 50% in breast carcinoma cells, with IC50 values ranging between 3 and 50 μM. These ER-α inhibitory compounds were further studied by molecular and cell biological techniques. Results: The compounds strongly inhibited ER-α activity at concentrations that yielded little or no nonspecific toxicity, but they produced only a modest inhibition of progesterone receptor activity. Importantly, the compounds blocked proliferation and inhibited ER-α activity about equally well in antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. Representative compounds disrupted the interaction of BRCA1 and ER-α in the cultured cells and blocked the interaction of ER-α with the estrogen response element. However, the compounds had no effect on the total cellular ER-α levels. Conclusions: These findings suggest that we have identified a new class of ER-α antagonists that work differently from conventional antiestrogens (eg, tamoxifen and fulvestrant). PMID:25264941

Calmodulin Lobes Facilitate Dimerization and Activation of Estrogen Receptor-α*

PubMed Central

Li, Zhigang; Zhang, Yonghong; Hedman, Andrew C.; Ames, James B.

2017-01-01

Estrogen receptor α (ER-α) is a nuclear hormone receptor that controls selected genes, thereby regulating proliferation and differentiation of target tissues, such as breast. Gene expression controlled by ER-α is modulated by Ca2+ via calmodulin (CaM). Here we present the NMR structure of Ca2+-CaM bound to two molecules of ER-α (residues 287–305). The two lobes of CaM bind to the same site on two separate ER-α molecules (residues 292, 296, 299, 302, and 303), which explains why CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu-11, Glu-14, Glu-84, and Glu-87) form salt bridges with key lysine residues in ER-α (Lys-299, Lys-302, and Lys-303), which is likely to prevent ubiquitination at these sites and inhibit degradation of ER-α. Transfection of cells with full-length CaM slightly increased the ability of estrogen to enhance transcriptional activation by ER-α of endogenous estrogen-responsive genes. By contrast, expression of either the N- or C-lobe of CaM abrogated estrogen-stimulated transcription of the estrogen responsive genes pS2 and progesterone receptor. These data suggest that CaM-induced dimerization of ER-α is required for estrogen-stimulated transcriptional activation by the receptor. In light of the critical role of ER-α in breast carcinoma, our data suggest that small molecules that selectively disrupt the interaction of ER-α with CaM may be useful in the therapy of breast carcinoma. PMID:28174300

Endoplasmic reticulum stress regulates tumor growth and anti-tumor immunity: a promising opportunity for cancer immunotherapy.

PubMed

Mohamed, Eslam; Cao, Yu; Rodriguez, Paulo C

2017-08-01

The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes. In order to cope with TME-induced ER stress, tumor and stromal cells initiate an adaptive response process that aims to resolve ER stress and to restore cellular homeostasis, which is referred as the unfolded protein responses (UPR). Paradoxically, the UPR can also induce cell death under severe and/or permanent ER stress. The UPR is started through three mediators, the activation of the inositol-requiring enzyme-1α, the pancreatic ER kinase-like ER kinase, and the activating transcription factor 6. In this minireview, we will discuss the pro- and anti-tumorigenic role of the UPR in cancer cells. In addition, we will describe the effects of the TME-induced ER stress in the immunosuppressive activity of tumor-infiltrating myeloid cells. Also, we will review the results of emerging therapeutic interventions that target ER stress and the UPR mediators in cancer. We postulate that the inhibition of ER stress or the UPR-related elements could represent a significant approach to increase the efficacy of various forms of cancer immunotherapy.

Irreversibility and critical current density of FeSr2ErCu2O6+y

NASA Astrophysics Data System (ADS)

Hata, Y.; Iida, I.; Mochiku, T.; Yasuoka, H.

2018-03-01

FeSr2ErCu2O6+y (ErFe1212) and non-superconducting FeSr2ErCu1.9Zn0.1O6+y were synthesized to study the property of the superconductivity and the irreversibility of ErFe1212. A large irreversibility in the temperature dependence of magnetization and a hysteresis in the magnetization curve were observed in ErFe1212. By comparison with non-superconducting FeSr2ErCu1.9Zn0.1O6+y, it was found that the most part of the hysteresis at high magnetic eld originates from the magnetism of Fe ion and some part of the hysteresis at low magnetic eld originates from the superconductivity. Using the magnetization curve of ErFe1212 and FeSr2ErCu1.9Zn0.1O6+y, the J c of ErFe1212 in individual grains at 10 K under 0.1 T was estimated by the Bean model and {J}\\text{c}\\text{intra} was 2.6 × 109 A/m2. The critical current density across inter-grain boundaries at 10 K estimated by V ‑ I measurement was {J}\\text{c}\\text{intra} = 5.7 × 104 A/m2. A large difference between {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} was observed in ErFe1212. {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} of ErFe1212 are 2.2 and 5.2 times larger than these of YFe1212, respectively.

Tributyltin-induced endoplasmic reticulum stress and its Ca(2+)-mediated mechanism.

PubMed

Isomura, Midori; Kotake, Yaichiro; Masuda, Kyoichi; Miyara, Masatsugu; Okuda, Katsuhiro; Samizo, Shigeyoshi; Sanoh, Seigo; Hosoi, Toru; Ozawa, Koichiro; Ohta, Shigeru

2013-10-01

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca(2+) signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca(2+) homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700nM TBT induced ER stress markers such as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca(2+) depletion, and to test this idea, we examined the effect of TBT on intracellular Ca(2+) concentration using fura-2 AM, a Ca(2+) fluorescent probe. TBT increased intracellular Ca(2+) concentration in a TBT-concentration-dependent manner, and Ca(2+) increase in 700nM TBT was mainly blocked by 50μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca(2+) concentration by releasing Ca(2+) from ER, thereby causing ER stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

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

Antonson, P., E-mail: per.antonson@ki.se; Omoto, Y.; Humire, P.

2012-08-10

Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established amore » new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.« less

Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

PubMed Central

Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

2014-01-01

Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

Endoplasmic Reticulum Transport of Glutathione by Sec61 Is Regulated by Ero1 and Bip.

PubMed

Ponsero, Alise J; Igbaria, Aeid; Darch, Maxwell A; Miled, Samia; Outten, Caryn E; Winther, Jakob R; Palais, Gael; D'Autréaux, Benoit; Delaunay-Moisan, Agnès; Toledano, Michel B

2017-09-21

In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H 2 O 2 -dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Hypothalamic Estrogen Receptors in Metabolic Regulation

PubMed Central

Frank, Aaron; Brown, Lynda M.; Clegg, Deborah J.

2014-01-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ”classical“ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. PMID:24882636

The role of hypothalamic estrogen receptors in metabolic regulation.

PubMed

Frank, Aaron; Brown, Lynda M; Clegg, Deborah J

2014-10-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two 'classical' estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1(-/-)); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Exciting transition metal doped dilute magnetic thin films: MgO:Er and ZnO:Er

NASA Astrophysics Data System (ADS)

Ćakıcı, T.; Sarıtaş, S.; Muǧlu, G. Merhan; Yıldırım, M.

2017-02-01

Erbium doped MgO and doped ZnO thin films have reasonably important properties applications in spintronic devices. These films were synthesized on glass substrates by Chemical Spray Pyrolysis (CSP) method. In the literature there has been almost no report on preparation of MgO:Er dilute magnetic thin films by means of CSP. Because doped thin films show different magnetic behaviors, depending upon the type of magnetic material ions, concentration of them, synthesis route and experimental conditions, synthesized MgO:Er and ZnO:Er films were compared to thin film properties. Optical analyses of the synthesized thin films were examined spectral absorption and transmittance measurements by UV-Vis double beam spectrophotometer technique. Structural analysis of the thin films was examined by using XRD, Raman Analysis, FE-SEM, EDX and AFM techniques. Also, magnetic properties of the MgO:Er and ZnO:Er films were investigated by vibrating sample magnetometer (VSM) which show that diamagnetic behavior of the MgO:Er thin film and ferromagnetic (FM) behavior of the ZnO:Er film were is formed.

Composite synchronization of three eccentric rotors driven by induction motors in a vibrating system

NASA Astrophysics Data System (ADS)

Kong, Xiangxi; Chen, Changzheng; Wen, Bangchun

2018-03-01

This paper addresses the problem of composite synchronization of three eccentric rotors (ERs) driven by induction motors in a vibrating system. The composite synchronous motion of three ERs is composed of the controlled synchronous motion of two ERs and the self-synchronous motion of the third ER. Combining an adaptive sliding mode control (ASMC) algorithm with a modified master-slave control structure, the controllers are designed to implement controlled synchronous motion of two ERs with zero phase difference. Based on Lyapunov stability theorem and Barbalat's lemma, the stability of the designed controllers is verified. On basis of controlled synchronization of two ERs, self-synchronization of the third ER is introduced to implement composite synchronous motion of three ERs. The feasibility of the proposed composite synchronization method is analyzed by numerical method. The effects of motor and structure parameters on composite synchronous motion are discussed. Experiments on a vibrating test bench driven by three ERs are operated to validate the effectiveness of the proposed composite synchronization method, including a comparison with self-synchronization method.

Role of dietary bioactive natural products in estrogen receptor-positive breast cancer

PubMed Central

Bak, Min Ji; Das Gupta, Soumyasri; Wahler, Joseph; Suh, Nanjoo

2016-01-01

Estrogen receptor (ER)-positive breast cancer, including luminal-A and -B, is the most common type of breast cancer. Extended exposure to estrogen is associated with an increased risk of breast cancer. Both ER-dependent and ER-independent mechanisms have been implicated in estrogen-mediated carcinogenesis. The ER-dependent pathway involves cell growth and proliferation triggered by the binding of estrogen to the ER. The ER-independent mechanisms depend on the metabolism of estrogen to generate genotoxic metabolites, free radicals and reactive oxygen species to induce breast cancer. A better understanding of the mechanisms that drive ER-positive breast cancer will help optimize targeted approaches to prevent or treat breast cancer. A growing emphasis is being placed on alternative medicine and dietary approaches toward the prevention and treatment of breast cancer. Many natural products and bioactive compounds found in foods have been shown to inhibit breast carcinogenesis via inhibition of estrogen induced oxidative stress as well as ER signaling. This review summarizes the role of bioactive natural products that are involved in the prevention and treatment of estrogen-related and ER-positive breast cancer. PMID:27016037

Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

PubMed

Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

2013-01-01

The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

Growth studies of erbium-doped GaAs deposited by metalorganic vapor phase epitaxy using noval cyclopentadienyl-based erbium sources

NASA Technical Reports Server (NTRS)

Redwing, J. M.; Kuech, T. F.; Gordon, D. C.; Vaartstra, B. A.; Lau, S. S.

1994-01-01

Erbium-doped GaAS layers were grown by metalorganic vapor phase epitaxy using two new sources, bis(i-propylcyclopentadienyl)cyclopentadienyl erbium and tris(t-butylcyclopentadienyl) erbium. Controlled Er doping in the range of 10(exp 17) - 10(exp 18)/cu cm was achieved using a relatively low source temperature of 90 C. The doping exhibits a second-order dependence on inlet source partial pressure, similar to behavior obtained with cyclopentadienyl Mg dopant sources. Equivalent amounts of oxygen and Er are present in 'as-grown' films indicating that the majority of Er dopants probably exist as Er-O complexes in the material. Er(+3) luminescence at 1.54 micrometers was measured from the as-grown films, but ion implantation of additional oxygen decreases the emission intensity. Electrical compensation of n-type GaAs layers codoped with Er and Si is directly correlated to the Er concentration is proposed to arise from the deep centers associated with Er which are responsible for a broad emission band near 0.90 micrometers present in the photoluminescence spectra of GaAs:Si, Er films.

Risk factors for breast cancer by oestrogen receptor status: a population-based case-control study.

PubMed Central

Cooper, J. A.; Rohan, T. E.; Cant, E. L.; Horsfall, D. J.; Tilley, W. D.

1989-01-01

Data from a population-based case-control study conducted in Adelaide, South Australia, and involving 451 case-control pairs, were analysed to determine whether the associations of menstrual, reproductive, dietary and other factors with risk of breast cancer differed by oestrogen receptor (ER) status. Data on ER status were available for 380 cases. The proportion of tumours which were ER+ increased with age, and there was a higher proportion of ER+ tumours in post-menopausal than in premenopausal women. Both oral contraceptive use (P = 0.055) and cigarette smoking (P = 0.047) were associated with increased (unadjusted) risk of ER- cancer, while having little association with risk of ER+ cancer. Most dietary factors had little association with risk of either cancer type, the main exception being the reduction in risk of ER- breast cancer with increasing beta-carotene intake (P for trend = 0.017). In general, however, links with the factors examined were not strong enough to suggest different causal pathways for ER- and ER+ breast cancer. PMID:2757918

Sigma-1 Receptor Chaperone at the ER-Mitochondrion Interface Mediates the Mitochondrion-ER-Nucleus Signaling for Cellular Survival

PubMed Central

Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

2013-01-01

The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus. PMID:24204710

Interleukin 17A exacerbates ER-stress-mediated inflammation of macrophages following ICH.

PubMed

Yang, Zhao; Liu, Qingjun; Shi, Hui; Jiang, Xuheng; Wang, Song; Lu, Yuanlan; Zhang, Ji; Huang, Xiaofei; Yu, Anyong

2018-05-30

IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measured in vitro. In addition, brain edema and brain injury in ICH mice were assessed in vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammation in vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice. In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH. Copyright © 2018. Published by Elsevier Ltd.

Adjustment of the evoked response sensitivity after hospital discharge in pacemaker patients with automatic ventricular threshold tracking activated.

PubMed

Schuchert, A; Ventura, R; Meinertz, T

2001-02-01

Automatic threshold tracking in cardiac pacemakers allows ventricular capture verification and self-adaptive pacing output regulation. The Autocapture algorithm detects the evoked response (ER) signal immediately after the pacing pulse to verify the efficacy of ventricular pacing. Before hospital delivery, the ER sensitivity must be programmed individually so that the pacemaker detects the ER signal adequately without sensing lead polarization. The aims of the study were to assess the frequency of patients in whom Autocapture could be activated and whether the ER sensitivity had to be adjusted after hospital discharge. The study included 44 patients who received the VVIR pacemaker Regency SR+ (St. Jude Medical) connected to the model 1450 T pacing lead. ER signal, lead polarization, and ER sensitivity were evaluated before hospital discharge and 1, 3, and 6 months after implantation. The system recommended activating Autocapture in 42 of 44 patients. The mean ER signal was 8.4+/-1.2 mV at discharge, 9.0+/-3.9 mV at month 1, 8.9+/-4.9 mV at month 3, and 9.3+/-4.5 mV at month 6. Polarization was 1.0+/-0.1 mV at discharge, 1.1+/-0.5 mV at month 1, 1.1+/-0.2 mV at month 3, and 1.1+/-0.5 mV at month 6. Mean ER sensitivity was 3.7+/-1.8 mV at discharge, 4.0+/-1.8 mV after 1, 4.1+/-2.2 mV after 3, and 4.1+/-1.8 mV after 6 months. ER sensitivity could remain unadjusted in 14 patients. Programming to a less sensitive ER setting from 2.9+/-1.2 mV to 4.3+/-1.5 mV was possible in 21 patients. Programming to a more sensitive ER setting from 4.1+/-1.1 mV to 2.5+/-0.9 mV was required in nine patients because of the decrease of the ER signal. The automatic threshold tracking algorithm Autocapture could be activated in 95% of patients. Programming to more sensitive ER settings was recommended in 21% of the patients after hospital discharge. Therefore, ER signal and polarization must be checked at each follow-up, as a decrease in ER signal amplitude can make reprogramming of the ER sensitivity necessary. There is no risk for the patient if the ER is not sensed, as high voltage backup stimulation is present.

78 FR 49492 - Combined Notice of Filings #1

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2013-08-14

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75 FR 33801 - Sunshine Act Meeting Notice

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2010-06-15

..., Inc. E-3 ER09-1050-000, ER09-1192-000.... Southwest Power Pool, Inc. E-4 OMITTED. E-5 ER09-1063-000..., Inc. E-7 ER10-1069-000 Southwest Power Pool, Inc. E-8 OMITTED. E-9 RM10-23-000 Transmission Planning... Owners. E-16 OMITTED. E-17 ER09-1051-000 ISO New England Inc. and New England Power Pool. E-18 EL10-52...

17 CFR Appendix 1 to Part 45 - Tables of Minimum Primary Economic Terms Data

Code of Federal Regulations, 2012 CFR

2012-04-01

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2013-04-01

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14 CFR Appendix C to Part 330 - Forms for Air Taxi Operators

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2011-01-01

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MicroRNAs meet calcium: joint venture in ER proteostasis.

PubMed

Finger, Fabian; Hoppe, Thorsten

2014-11-04

The endoplasmic reticulum (ER) is a cellular compartment that has a key function in protein translation and folding. Maintaining its integrity is of fundamental importance for organism's physiology and viability. The dynamic regulation of intraluminal ER Ca(2+) concentration directly influences the activity of ER-resident chaperones and stress response pathways that balance protein load and folding capacity. We review the emerging evidence that microRNAs play important roles in adjusting these processes to frequently changing intracellular and environmental conditions to modify ER Ca(2+) handling and storage and maintain ER homeostasis. Copyright © 2014, American Association for the Advancement of Science.

Ero1alpha requires oxidizing and normoxic conditions to localize to the mitochondria-associated membrane (MAM).

PubMed

Gilady, Susanna Y; Bui, Michael; Lynes, Emily M; Benson, Matthew D; Watts, Russell; Vance, Jean E; Simmen, Thomas

2010-09-01

Protein secretion from the endoplasmic reticulum (ER) requires the enzymatic activity of chaperones and oxidoreductases that fold polypeptides and form disulfide bonds within newly synthesized proteins. The best-characterized ER redox relay depends on the transfer of oxidizing equivalents from molecular oxygen through ER oxidoreductin 1 (Ero1) and protein disulfide isomerase to nascent polypeptides. The formation of disulfide bonds is, however, not the sole function of ER oxidoreductases, which are also important regulators of ER calcium homeostasis. Given the role of human Ero1alpha in the regulation of the calcium release by inositol 1,4,5-trisphosphate receptors during the onset of apoptosis, we hypothesized that Ero1alpha may have a redox-sensitive localization to specific domains of the ER. Our results show that within the ER, Ero1alpha is almost exclusively found on the mitochondria-associated membrane (MAM). The localization of Ero1alpha on the MAM is dependent on oxidizing conditions within the ER. Chemical reduction of the ER environment, but not ER stress in general leads to release of Ero1alpha from the MAM. In addition, the correct localization of Ero1alpha to the MAM also requires normoxic conditions, but not ongoing oxidative phosphorylation.

Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells

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

Hsin, I-Lun; Hsiao, Yueh-Chieh; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

2012-09-15

Endoplasmic reticulum (ER) stress is activated under severe cellular conditions. GADD153, a member of the C/EBP family, is an unfolded protein response (UPR) responsive transcription factor. Increased levels of lipocalin 2, an acute phase protein, have been found in several epithelial cancers. The aim of this study is to investigate the function of lipocalin 2 in lung cancer cells under ER stress. Treatment with thapsigargin, an ER stress activator, led to increases in cytotoxicity, ER stress, apoptosis, and lipocalin 2 expression in A549 cells. GADD153 silencing decreased lipocalin 2 expression in A549 cells. On chromatin immunoprecipitation assay, ER stress increasedmore » GADD153 DNA binding to lipocalin 2 promoter. Furthermore, silencing of lipocalin 2 mitigated ER stress-mediated apoptosis in A549 cells. Our findings demonstrated that lipocalin 2 is a new GADD153 target gene that mediates ER stress-induced apoptosis. Highlights: ► We demonstrate that Lipocalin 2 is a new GADD153 target gene. ► Lipocalin 2 mediates ER stress-induced apoptosis. ► ER stress-induced lipocalin 2 expression is calcium-independent in A549 cells. ► Lipocalin 2 dose not play a major role in ER stress-induced autophagy.« less

Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway.

PubMed

Larios, Jorge A; Jausoro, Ignacio; Benitez, Maria-Luisa; Bronfman, Francisca C; Marzolo, Maria-Paz

2014-09-19

ApoER2 and the neurotrophin receptors Trk and p75(NTR) are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75(NTR) are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75(NTR) mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors. We found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75(NTR). Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF). Our results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

PubMed Central

Freund, Ariane; Chauveau, Corine; Brouillet, Jean-Paul; Lucas, Annick; Lacroix, Matthieu; Licznar, Anne; Vignon, Françoise; Lazennec, Gwendal

2003-01-01

Estrogen receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that IL-8 was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of interleukin-8 (IL-8), but not with IL-8 receptors levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by 2 fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER-status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness. PMID:12527894

75 FR 3225 - Notice of Commission Staff Attendance at Organization of MISO States and Midwest ISO Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

.... Docket No. ER08-1043, Midwest Independent Transmission System Operator, Inc. Docket No. ER08-1074... Operator, Inc. Docket No. ER09-1074, Midwest Independent Transmission System Operator, Inc. Docket No. ER09...

Emerging themes of ER organization in the development and maintenance of axons

PubMed Central

Renvoisé, Benoît; Blackstone, Craig

2010-01-01

The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network of smooth tubules extending throughout the cell. Though protein biosynthesis, transport, and quality control in the ER have been extensively studied, mechanisms underlying the heterogeneous architecture of the ER have been clarified more recently. These insights have increased interest in ER morphology changes associated with the development of neuronal axons and dendrites as well as their integration with pre- and postsynaptic signaling pathways. A number of proteins involved in shaping and distributing the ER network are mutated in neurological disorders, particularly the hereditary spastic paraplegias, emphasizing the importance of proper ER morphology for the establishment and maintenance of highly-polarized neurons. PMID:20678923

Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and ESR1 mRNA Expression in Breast Tumors.

PubMed

Butler, Eboneé N; Bensen, Jeannette T; Chen, Mengjie; Conway, Kathleen; Richardson, David B; Sun, Xuezheng; Geradts, Joseph; Olshan, Andrew F; Troester, Melissa A

2018-01-01

Background: Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen receptor-positive (ER + ) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression. Methods: We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (±) and continuous measures for ER protein, ESR1 mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors. We used logistic and linear regression models to estimate temporal and dose-dependent associations between smoking and ER measures. Results: The odds of ER + , ESR1 + , and LS + tumors among current smokers (at the time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of nonsmokers. Quantitative levels of ESR1 were highest among current smokers compared with never smokers overall [mean (log 2 ) = 9.2 vs. 8.7, P < 0.05] and among ER + cases; however, we did not observe associations between smoking measures and continuous ER protein expression. Conclusions: In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER + , ESR1 + , and LS + subtype. Current smoking was associated with elevated ESR1 mRNA levels and an elevated LS, but not with altered ER protein. Impact: A multigene LS and single-gene ESR1 mRNA may capture tumor changes associated with smoking. Cancer Epidemiol Biomarkers Prev; 27(1); 67-74. ©2017 AACR . ©2017 American Association for Cancer Research.

Dancing with the Stars: Using Image Analysis to Study the Choreography of the Endoplasmic Reticulum and Its Partners and of Movement Within Its Tubules.

PubMed

Griffing, Lawrence R

2018-01-01

In this chapter, approaches to the image analysis of the choreography of the plant endoplasmic reticulum (ER) labeled with fluorescent fusion proteins ("stars," if you wish) are presented. The approaches include the analyses of those parts of the ER that are attached through membrane contact sites to moving or nonmoving partners (other "stars"). Image analysis is also used to understand the nature of the tubular polygonal network, the hallmark of this organelle, and how the polygons change over time due to tubule sliding or motion. Furthermore, the remodeling polygons of the ER interact with regions of fundamentally different topology, the ER cisternae, and image analysis can be used to separate the tubules from the cisternae. ER cisternae, like polygons and tubules, can be motile or stationary. To study which parts are attached to nonmoving partners, such as domains of the ER that form membrane contact sites with the plasma membrane/cell wall, an image analysis approach called persistency mapping has been used. To study the domains of the ER that are moving rapidly and streaming through the cell, the image analysis of optic flow has been used. However, optic flow approaches confuse the movement of the ER itself with the movement of proteins within the ER. As an overall measure of ER dynamics, optic flow approaches are of value, but their limitation as to what exactly is "flowing" needs to be specified. Finally, there are important imaging approaches that directly address the movement of fluorescent proteins within the ER lumen or in the membrane of the ER. Of these, fluorescence recovery after photobleaching (FRAP), inverse FRAP (iFRAP), and single particle tracking approaches are described.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day—A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia

PubMed Central

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-01-01

Background Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3–12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. Methods In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Results Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, –11.4 (20.81); paliperidone ER 1.5 mg group, –8.9 (23.31); and paliperidone ER 6 mg group, –15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group—headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group—insomnia (13.6%); and paliperidone ER 6 mg group—headache (11.4%), insomnia (10%), and tremor (10%). Conclusions In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo. PMID:27738355

Er{sub 1.33}Pt{sub 3}Ga{sub 8}: A modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type

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

Oswald, Iain W.H.; Gourdon, Olivier; Bekins, Amy

Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were synthesized in a molten Ga flux. Er{sub 1.33}Pt{sub 3}Ga{sub 8} can be considered to be a modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type, where the partial occupancies are ordered. Indeed, the presence of weak satellite reflections indicates a complex organization and distribution of the Er and Ga atoms within the [ErGa] slabs. The structure has been solved based on single crystal X-ray diffraction data in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*. Precession images also indicate diffusion in the perpendicular direction indicating a partial disorder ofmore » this arrangement from layer to layer. In addition, Er{sub 1.33}Pt{sub 3}Ga{sub 8} shows antiferromagnetic ordering at T{sub N}~5 K. - Graphical abstract: A precession image of the hk0 zone showing weak, periodic, unindexed reflections indicating modulation and representation of the commensurate [ErGa] layer showing the waving modulated occupation. - Highlights: • Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were grown from gallium flux. • The structure of Er{sub 1.33}Pt{sub 3}Ga{sub 8} is compared to Er{sub 4}Pt{sub 9}Al{sub 24}. • Structure has been solved in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*.« less

Self-focused cognitive emotion regulation style as associated with widespread diminished EEG fractal dimension.

PubMed

Bornas, Xavier; Tortella-Feliu, Miquel; Balle, Maria; Llabrés, Jordi

2013-01-01

The cognitive regulation of emotions is important for human adaptation. Self-focused emotion regulation (ER) strategies have been linked to the development and persistence of anxiety and depression. A vast array of research has provided valuable knowledge about the neural correlates of the use of specific self-focused ER strategies; however, the resting neural correlates of cognitive ER styles, which reflect an individual's disposition to engage in different forms of ER in order to manage distress, are largely unknown. In this study, associations between theoretically negative ER style (self-focused or not) and the complexity (fractal dimension, FD) of the resting EEG at frontal, central, parietal, and occipital regions were investigated in 58 healthy volunteers. The Cognitive Emotion Regulation Questionnaire was used as the self-report measure of ER style. Results showed that a diminished FD over the scalp significantly correlated with self-focused ER style scores, even after controlling for negative affect, which has been also considered to influence the use of ER strategies. The lower the EEG FD, the higher were the self-focused ER style scores. Correlational analyses of specific self-focused ER strategies showed that self-blaming and rumination were negatively associated with diminished FD of the EEG, but catastrophizing and blaming others were not. No significant correlations were found for ER strategies more focused on situation or others. Results are discussed within the self-organized criticality theory of brain dynamics: The diminished FD of the EEG may reflect a disposition to engage in self-focused ER strategies as people prone to ruminate and self-blame show a less complex resting EEG activity, which may make it more difficult for them to exit their negative emotional state.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day-A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia.

PubMed

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-05-15

Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3-12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, -11.4 (20.81); paliperidone ER 1.5 mg group, -8.9 (23.31); and paliperidone ER 6 mg group, -15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group-headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group-insomnia (13.6%); and paliperidone ER 6 mg group-headache (11.4%), insomnia (10%), and tremor (10%). In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo.

The effects of energy transfer on the Er3+ 1.54 μm luminescence in nanostructured Y2O3 thin films with heterogeneously distributed Yb3+ and Er3+ codopants

NASA Astrophysics Data System (ADS)

Hoang, J.; Schwartz, Robert N.; Wang, Kang L.; Chang, J. P.

2012-09-01

We report the effects of heterogeneous Yb3+ and Er3+ codoping in Y2O3 thin films on the 1535 nm luminescence. Yb3+:Er3+:Y2O3 thin films were deposited using sequential radical enhanced atomic layer deposition. The Yb3+ energy transfer was investigated for indirect and direct excitation of the Yb 2F7/2 state using 488 nm and 976 nm sources, respectively, and the trends were described in terms of Forster and Dexter's resonant energy transfer theory and a macroscopic rate equation formalism. The addition of 11 at. % Yb resulted in an increase in the effective Er3+ photoluminescence (PL) yield at 1535 nm by a factor of 14 and 42 under 488 nm and 976 nm excitations, respectively. As the Er2O3 local thickness was increased to greater than 1.1 Å, PL quenching occurred due to strong local Er3+ ↔ Er3+ excitation migration leading to impurity quenching centers. In contrast, an increase in the local Yb2O3 thickness generally resulted in an increase in the effective Er3+ PL yield, except when the Er2O3 and Yb2O3 layers were separated by more than 2.3 Å or were adjacent, where weak Yb3+ ↔ Er3+ coupling or strong Yb3+ ↔ Yb3+ interlayer migration occurred, respectively. Finally, it is suggested that enhanced luminescence at steady state was observed under 488 nm excitation as a result of Er3+ → Yb3+ energy back transfer coupled with strong Yb3+ ↔ Yb3+ energy migration.

Laser reduction of specific microorganisms in the periodontal pocket using Er:YAG and Nd:YAG lasers: a randomized controlled clinical study.

PubMed

Grzech-Leśniak, K; Sculean, A; Gašpirc, Boris

2018-05-15

The objective of this study was to evaluate the microbiological and clinical outcomes following nonsurgical treatment by either scaling and root planing, combination of Nd:YAG and Er:YAG lasers, or by Er:YAG laser treatment alone. The study involved 60 patients with generalized chronic periodontitis, randomly assigned into one of three treatment groups of 20 patients. The first group received scaling and root planing by hand instruments (SRP group), the second group received Er:YAG laser treatment alone (Er group), and the third group received combined treatment with Nd:YAG and Er:YAG lasers (NdErNd group). Microbiological samples, taken from the periodontal pockets at baseline and 6 months after treatments, were assessed with PET Plus tests. The combined NdErNd laser (93.0%), followed closely by Er:YAG laser (84.9%), treatment resulted in the highest reduction of all bacteria count after 6 months, whereas SRP (46.2%) failed to reduce Treponema denticola, Peptostreptococcus micros, and Capnocytophaga gingivalis. Full-mouth plaque and bleeding on probing scores dropped after 6 months and were the lowest in both laser groups. The combination of NdErNd resulted in higher probing pocket depth reduction and gain of clinical attachment level (1.99 ± 0.23 mm) compared to SRP (0.86 ± 0.13 mm) or Er:YAG laser alone (0.93 ± 0.20 mm) in 4-6 mm-deep pockets. Within their limits, the present results provide support for the combination of Nd:YAG and Er:YAG lasers to additionally improve the microbiological and clinical outcomes of nonsurgical periodontal therapy in patients with moderate to severe chronic periodontitis.

Near Infrared Quantum Cutting Luminescence of Er3+/Tm3+ Ion Pairs in a Telluride Glass.

PubMed

Chen, Xiaobo; Li, Song; Hu, Lili; Wang, Kezhi; Zhao, Guoying; He, Lizhu; Liu, Jinying; Yu, Chunlei; Tao, Jingfu; Lin, Wei; Yang, Guojian; Salamo, Gregory J

2017-05-16

The multiphoton near-infrared, quantum cutting luminescence in Er 3+ /Tm 3+ co-doped telluride glass was studied. We found that the near-infrared 1800-nm luminescence intensity of (A) Er 3+ (8%)Tm 3+ (0.5%):telluride glass was approximately 4.4 to 19.5 times larger than that of (B) Tm 3+ (0.5%):telluride glass, and approximately 5.0 times larger than that of (C) Er 3+ (0.5%):telluride glass. Additionally, the infrared excitation spectra of the 1800 nm luminescence, as well as the visible excitation spectra of the 522 nm and 652 nm luminescence, of (A) Er 3+ (8%)Tm 3+ (0.5%):telluride glass are very similar to those of Er 3+ ions in (C) Er 3+ (0.5%):telluride glass, with respect to the shapes of their excitation spectral waveforms and peak wavelengths. Moreover, we found that there is a strong spectral overlap and energy transfer between the infrared luminescence of Er 3+ donor ions and the infrared absorption of Tm 3+ acceptor ions. The efficiency of this energy transfer { 4 I 13/2 (Er 3+ ) →  4 I 15/2 (Er 3+ ), 3 H 6 (Tm 3+ ) →  3 F 4 (Tm 3+ )} between the Er 3+ and Tm 3+ ions is approximately 69.8%. Therefore, we can conclude that the observed behaviour is an interesting multiphoton, near-infrared, quantum cutting luminescence phenomenon that occurs in novel Er 3+ -Tm 3+ ion pairs. These findings are significant for the development of next-generation environmentally friendly germanium solar cells, and near-to-mid infrared (1.8-2.0 μm) lasers pumped by GaN light emitting diodes.

Er-doped sesquioxides for 1.5-micron lasers - spectroscopic comparisons

NASA Astrophysics Data System (ADS)

Merkle, Larry D.; Ter-Gabrielyan, Nikolay

2013-05-01

Due to the favorable thermal properties of sesquioxides as hosts for rare earth laser ions, we have recently studied the spectroscopy of Er:Lu2O3 in the 1400-1700 nm wavelength range, and here report its comparison with our earlier results on Er:Y2O3 and Er:Sc2O3. These studies include absorption and fluorescence spectra, fluorescence lifetimes, and inference of absorption and stimulated emission cross sections, all as a function of temperature. At room temperature, optical absorption limits practical laser operation to wavelengths longer than about 1620 nm. In that spectral range, the strongest stimulated emission peak is that at 1665 nm in Er:Sc2O3, with an effective cross section considerably larger than those of Er:Y2O3 and Er:Lu2O3. At 77K, the absorption is weak enough for efficient laser operation at considerably shorter wavelengths, where there are peaks with much larger stimulated emission cross sections. The three hosts all have peaks near 1575-1580 nm with comparably strong cross sections. As we have reported earlier, it is possible to lase even shorter wavelengths efficiently at this temperature, in particular the line at 1558 nm in Er:Sc2O3. Our new spectroscopic studies of Er:Lu2O3 indicate that its corresponding peak, like that of Er:Sc2O3, has a less favorable ratio of stimulated emission to absorption cross sections. Reasons for the differences will be discussed. We conclude that for most operating scenarios, Er:Sc2O3 is the most promising of the Er-doped sesquioxides studied for laser operation around 1.5-1.6 microns.

Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network

PubMed Central

Park, Seong H.; Zhu, Peng-Peng; Parker, Rell L.; Blackstone, Craig

2010-01-01

Hereditary spastic paraplegias (HSPs; SPG1–45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and atlastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins atlastin-1, spastin, and REEP1 interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP. PMID:20200447

Estrogen receptors in gastric cancer: Advances and perspectives.

PubMed

Ur Rahman, Muhammad Saif; Cao, Jiang

2016-02-28

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

Cubic crystalline erbium oxide growth on GaN(0001) by atomic layer deposition

NASA Astrophysics Data System (ADS)

Chen, Pei-Yu; Posadas, Agham B.; Kwon, Sunah; Wang, Qingxiao; Kim, Moon J.; Demkov, Alexander A.; Ekerdt, John G.

2017-12-01

Growth of crystalline Er2O3, a rare earth sesquioxide, on GaN(0001) is described. Ex situ HCl and NH4OH solutions and an in situ N2 plasma are used to remove impurities on the GaN surface and result in a Ga/N stoichiometry of 1.02. Using atomic layer deposition with erbium tris(isopropylcyclopentadienyl) [Er(iPrCp)3] and water, crystalline cubic Er2O3 (C-Er2O3) is grown on GaN at 250 °C. The orientation relationships between the C-Er2O3 film and the GaN substrate are C-Er2O3(222) ǁ GaN(0001), C-Er2O3⟨-440⟩ ǁ GaN ⟨11-20⟩, and C-Er2O3⟨-211⟩ ǁ GaN ⟨1-100⟩. Scanning transmission electron microscopy and electron energy loss spectroscopy are used to examine the microstructure of C-Er2O3 and its interface with GaN. With post-deposition annealing at 600 °C, a thicker interfacial layer is observed, and two transition layers, crystalline GaNwOz and crystalline GaErxOy, are found between GaN and C-Er2O3. The tensile strain in the C-Er2O3 film is studied with x-ray diffraction by changes in both out-of-plane and in-plane d-spacing. Fully relaxed C-Er2O3 films on GaN are obtained when the film thickness is around 13 nm. Additionally, a valence band offset of 0.7 eV and a conduction band offset of 1.2 eV are obtained using x-ray photoelectron spectroscopy.

Structural and optical studies of Er3+-doped alkali/alkaline oxide containing zinc boro-aluminosilicate glasses for 1.5 μm optical amplifier applications

NASA Astrophysics Data System (ADS)

Kaky, Kawa M.; Lakshminarayana, G.; Baki, S. O.; Lira, A.; Caldiño, U.; Meza-Rocha, A. N.; Falcony, C.; Kityk, I. V.; Taufiq-Yap, Y. H.; Halimah, M. K.; Mahdi, M. A.

2017-07-01

In the present work, we report on the optical spectral properties of Er3+-doped zinc boro-aluminosilicate glasses with an addition of 10 mol % alkali/alkaline modifier regarding the fabrication of new optical materials for optical amplifiers. A total of 10 glasses were prepared using melt-quenching technique with the compositions (40-x)B2O3 - 10SiO2 - 10Al2O3 - 30ZnO - 10Li2O - xEr2O3 and (40-x)B2O3 - 10SiO2 - 10Al2O3 - 30ZnO - 10MgO - xEr2O3 (x = 0.1, 0.25, 0.5, 1.0, and 2.0 mol %). We confirm the amorphous-like structure for all the prepared glasses using X-ray diffraction (XRD). To study the functional groups of the glass composition after the melt-quenching process, Raman spectroscopy was used, and various structural units such as triangular and tetrahedral-borates (BO3 and BO4) have been identified. All the samples were characterized using optical absorption for UV, visible and NIR regions. Judd-Ofelt (JO) intensity parameters (Ωλ, λ = 2, 4 and 6) were calculated from the optical absorption spectra of two glasses LiEr 2.0 and MgEr 2.0 (doped with 2 mol % of Er3+). JO parameters for LiEr 2.0 and MgEr 2.0 glasses follow the trend as Ω6>Ω2>Ω4. Using Judd-Ofelt intensity parameters, we obtained radiative probability A (S-1), branching ratios (β), radiative decay lifetimes τrad (μs) of emissions from excited Er+3 ions in LiEr 2.0 and MgEr 2.0 to all lower levels. Quantum efficiency (η) of 4I13/2 and 4S3/2 levels for LiEr 2.0 and MgEr 2.0 with and without 4D7/2 level was calculated using the radiative decay lifetimes τrad. (μs) and measured lifetimes τexp. (μs). We measured the visible photoluminescence under 377 nm excitation for both LiEr and MgEr glass series within the region 390-580 nm. Three bands were observed in the visible region at 407 nm, 530 nm, and 554 nm, as a result of 2H9/2 → 4I15/2, 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 transitions, respectively. Decay lifetimes for emissions at 407 nm, 530 nm, and 554 nm were measured and they show single exponential behavior for all the LiEr and MgEr glass series. From the photoluminescence and radiative decay lifetimes (τrad), we calculated the full-width at half-maximum (FWHM), emission cross-section (σPE) and bandwidth gain (FWHM × σPE) parameters. Near-infrared photoluminescence under 980 nm excitation was measured for all the LiEr and MgEr glass series in the region 1420-1620 nm. NIR emissions show a broadband centered at ∼1530 nm due to the transition of Er3+: 4I13/2 → 4I15/2. Decay lifetimes for NIR emission at ∼1530 nm were measured and they show a quite exponential nature for all the LiEr and MgEr glass series. From the NIR emission spectra and decay lifetimes, we calculated the full-width at half-maximum (FWHM), the emission cross-section (σPE) and the bandwidth gain (FWHM × σPE) for the NIR emission and it shows FWHM of 50-70 nm for prepared glasses, emission cross-section of (∼3.5) × 10-20 cm2, while bandwidth gain was (∼25) × 10-26 cm3.

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States

PubMed Central

Iwanicki, Janetta L.; Severtson, S. Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J.; Ellis, Matthew S.; Kurtz, Steven P.; Buttram, Mance E.; Dart, Richard C.

2016-01-01

Background Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Methods Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. Results From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Conclusions Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations. PMID:27936038

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

PubMed

Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

2016-01-01

Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

Erbium:Yttrium Aluminum Garnet Laser-Activated Sodium Hypochlorite Irrigation: A Promising Procedure for Minimally Invasive Endodontics.

PubMed

Cheng, Xiaogang; Tian, Tiantian; Tian, Yu; Xiang, Doudou; Qiu, Jun; Liu, Xiaohua; Yu, Qing

2017-12-01

This study was to evaluate the potential of Erbium:Yttrium Aluminum Garnet laser-activated sodium hypochlorite irrigation (Er:YAG + NaOCl) for minimally invasive endodontics (MIE). Er:YAG laser irradiation can dramatically enhance the penetration of NaOCl, which may be a promising protocol for MIE. Extracted human teeth were contaminated with Enterococcus faecalis for 4 weeks. The infected canals were then shaped to different apical terminal working widths (ATWW, 15#/0.04, 20#/0.04, 25#/0.04, 30#/0.04, and 40#/0.04) and treated with either Er:YAG + NaOCl (0.3 W, 20 sec) or NaOCl alone. Then, the ATWW were fixed at 15#/0.04, and the canals were treated with Er:YAG + NaOCl at 0.3 W for 40 and 60 sec, or at 0.5 and 1.0 W for 20 sec. Finally, bacterial reductions were evaluated using the cell count method. Er:YAG + NaOCl showed a higher disinfection efficacy at each ATWW compared with NaOCl alone (p < 0.001). The maximum bacterial reduction was 99.9% for the 40#/Er:YAG + NaOCl group and 93.6% for the 40#/NaOCl group. To achieve similar disinfection efficacy, the Er:YAG + NaOCl group needed a smaller ATWW than the NaOCl group. At a fixed ATWW, increasing the output power of the Er:YAG laser was more effective than increasing the radiation time to improve the disinfection efficacy of Er:YAG + NaOCl. The 15#/Er:YAG + NaOCl group reached the maximum bacterial reduction of 99.2% when the Er:YAG laser was activated at 1.0 W for 20 sec. The 15#/Er:YAG + NaOCl with the Er:YAG laser irradiation at 1.0 W for 20 sec may be considered a promising procedure for MIE.

Evaluation of the bond strength of resin cements used to lute ceramics on laser-etched dentin.

PubMed

Giray, Figen Eren; Duzdar, Lale; Oksuz, Mustafa; Tanboga, Ilknur

2014-07-01

The purpose of this study was to investigate the shear bond strength (SBS) of two different adhesive resin cements used to lute ceramics on laser-etched dentin. Erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser irradiation has been claimed to improve the adhesive properties of dentin, but results to date have been controversial, and its compatibility with existing adhesive resin cements has not been conclusively determined. Two adhesive cements, one "etch-and-rinse" [Variolink II (V)] and one "self-etch" [Clearfil Esthetic Cement (C)] luting cement, were used to lute ceramic blocks (Vita Celay Blanks, Vita) onto dentin surfaces. In total, 80 dentin specimens were distributed randomly into eight experimental groups according to the dentin surface-etching technique used Er,Cr:YSGG laser and Er:YAG laser: (1) 37% orthophosphoric acid+V (control group), (2) Er,Cr:YSGG laser+V, (3) Er,Cr:YSGG laser+acid+V, (4) Er:YAG laser+V, (5) Er:YAG laser+acid+V, (6) C, (7) Er,Cr:YSGG laser+C, and (8) Er:YAG laser+C. Following these applications, the ceramic discs were bonded to prepared surfaces and were shear loaded in a universal testing machine until fracture. SBS was recorded for each group in MPa. Shear test values were evaluated statistically using the Mann-Whitney U test. No statistically significant differences were evident between the control group and the other groups (p>0.05). The Er,Cr:YSGG laser+A+V group demonstrated significantly higher SBS than did the Er,Cr:YSGG laser+V group (p=0.034). The Er,Cr:YSGG laser+C and Er:YAG laser+C groups demonstrated significantly lower SBS than did the C group (p<0.05). Dentin surfaces prepared with lasers may provide comparable ceramic bond strengths, depending upon the adhesive cement used.

Verification and Improvement of ERS-1/2 Altimeter Geophysical Data Records for Global Change Studies

NASA Technical Reports Server (NTRS)

Shum, C. K.

2000-01-01

This Final Technical Report summarizes the research work conducted under NASA's Physical Oceanography Program entitled, Verification And Improvement Of ERS-112 Altimeter Geophysical Data Recorders For Global Change Studies, for the time period from January 1, 2000 through June 30, 2000. This report also provides a summary of the investigation from July 1, 1997 - June 30, 2000. The primary objectives of this investigation include verification and improvement of the ERS-1 and ERS-2 radar altimeter geophysical data records for distribution of the data to the ESA-approved U.S. ERS-1/-2 investigators for global climate change studies. Specifically, the investigation is to verify and improve the ERS geophysical data record products by calibrating the instrument and assessing accuracy for the ERS-1/-2 orbital, geophysical, media, and instrument corrections. The purpose is to ensure that the consistency of constants, standards and algorithms with TOPEX/POSEIDON radar altimeter for global climate change studies such as the monitoring and interpretation of long-term sea level change. This investigation has provided the current best precise orbits, with the radial orbit accuracy for ERS-1 (Phases C-G) and ERS-2 estimated at the 3-5 cm rms level, an 30-fold improvement compared to the 1993 accuracy. We have finalized the production and verification of the value-added ERS-1 mission (Phases A, B, C, D, E, F, and G), in collaboration with JPL PODAAC and the University of Texas. Orbit and data verification and improvement of algorithms led to the best data product available to-date. ERS-2 altimeter data have been improved and we have been active on Envisat (2001 launch) GDR algorithm review and improvement. The data improvement of ERS-1 and ERS-2 led to improvement in the global mean sea surface, marine gravity anomaly and bathymetry models, and a study of Antarctica mass balance, which was published in Science in 1998.

Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

PubMed Central

Babayan, Anna; Hannemann, Juliane; Spötter, Julia; Müller, Volkmar

2013-01-01

Background Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER) positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs). Methods A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient) were isolated and underwent whole genome amplification and ESR1 gene mutation analysis. Results CTCs were detected in blood of 16 from 35 analyzed patients (46%), with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69%) of the CTC positive cases, including blood samples with only ER-negative CTCs (19%) and samples with both ER-positive and ER-negative CTCs (50%). No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found. Conclusion CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process. PMID:24058649

75 FR 23262 - Notice of Attendance at the Arkansas Public Service Commission Technical Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... Power Pool, Inc. Docket No. ER10-696, Southwest Power Pool, Inc. Docket No. ER10-697, Southwest Power Pool, Inc. Docket No. ER10-698, Southwest Power Pool, Inc. Docket No. ER10-700, Southwest Power Pool...

77 FR 64502 - Notice of Compliance Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Compliance Filings Docket Nos. Northwestern Corporation (South Dakota). ER13-62-000 PacificCorp ER13-64-000 Deseret Generation & Transmission ER13-65-000 Cooperative, Inc.. Northwestern Corporation (Montana)...... ER13-67-000 Portland General...

Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors

PubMed Central

2013-01-01

In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric. PMID:23294730

Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors.

PubMed

Chen, Fa-Hsyang; Her, Jim-Long; Shao, Yu-Hsuan; Matsuda, Yasuhiro H; Pan, Tung-Ming

2013-01-08

In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric.

Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster

PubMed Central

Lindström, Riitta; Lindholm, Päivi; Kallijärvi, Jukka; Palgi, Mari; Saarma, Mart; Heino, Tapio I.

2016-01-01

Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR. PMID:26975047

Natural products targeting ER stress pathway for the treatment of cardiovascular diseases.

PubMed

Choy, Ker Woon; Murugan, Dharmani; Mustafa, Mohd Rais

2018-04-21

Endoplasmic reticulum (ER) is the main organelle for the synthesis, folding, and processing of secretory and transmembrane proteins. Pathological stimuli including hypoxia, ischaemia, inflammation and oxidative stress interrupt the homeostatic function of ER, leading to accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers a complex signalling network referred as the unfolded protein response (UPR). Extensive studies have demonstrated that ER stress plays an important role in the pathogenesis of various cardiovascular diseases such as heart failure, ischemic heart disease and atherosclerosis. The importance of natural products in modern medicine are well recognized and continues to be of interests as a source of novel lead compounds. Natural products targeting components of UPR and reducing ER stress offers an innovative strategic approach to treat cardiovascular diseases. In this review, we discussed several therapeutic interventions using natural products with potential cardiovascular protective properties targeting ER stress signalling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

Specific emotion regulation impairments in major depression and anorexia nervosa.

PubMed

Brockmeyer, Timo; Bents, Hinrich; Holtforth, Martin Grosse; Pfeiffer, Nils; Herzog, Wolfgang; Friederich, Hans-Christoph

2012-12-30

Emotion regulation (ER) difficulties have been considered to play an important role in the development and maintenance of various mental disorders such as depression and anorexia nervosa. However, previous research has failed to provide detailed insight into the disorder-specificity of ER difficulties. Therefore, the present study investigated specific ER difficulties in female samples of patients with major depression, patients with anorexia nervosa, and healthy controls (total sample: N=140). As compared to healthy controls, both clinical groups reported greater ER difficulties concerning both the experience and the differentiation as well as the attenuation and the modulation of emotions. Patients in both clinical groups reported comparably elevated ER difficulties regarding the experience and differentiation of emotions. However, depressed patients reported stronger ER difficulties regarding the attenuation and modulation of emotions as compared to patients with anorexia nervosa. These findings support the notion of ER difficulties as transdiagnostic phenomena, and suggest that depression may be characterized by broader and greater ER difficulties than anorexia nervosa. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Survival with breast cancer: the importance of estrogen receptor quantity.

PubMed

Shek, L L; Godolphin, W

1989-02-01

The survival of 1184 British Columbian women whose primary breast cancers were diagnosed and assayed for estrogen receptor (ER) between 1975 and 1981 was studied. Median follow-up was 60 months. ER concentrations yielded greater prognostic information than simple positive and negative categories. When ER data were divided into four strata: less than or equal to 1, 2-9, 10-159 and greater than or equal to 160 fmol/mg cytosol protein, the association of higher ER with prolonged survival was highly significant (P less than 0.0001) and independent of TNM stage, nodal status and menopausal status. ER less than or equal to 1 and ER = 2-9 groups were distinct with respect to overall disease-specific survival. Patient age did not predict survival when controlled for ER. Prolonged recurrence-free survival was associated with higher ER (P = 0.0001) for at least 5 years after diagnosis. This significant trend persisted after adjustments for nodal status, TNM stage, menopausal status and the type of systemic adjuvant therapy.

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

PubMed

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

A hierarchical exact accelerated stochastic simulation algorithm

NASA Astrophysics Data System (ADS)

Orendorff, David; Mjolsness, Eric

2012-12-01

A new algorithm, "HiER-leap" (hierarchical exact reaction-leaping), is derived which improves on the computational properties of the ER-leap algorithm for exact accelerated simulation of stochastic chemical kinetics. Unlike ER-leap, HiER-leap utilizes a hierarchical or divide-and-conquer organization of reaction channels into tightly coupled "blocks" and is thereby able to speed up systems with many reaction channels. Like ER-leap, HiER-leap is based on the use of upper and lower bounds on the reaction propensities to define a rejection sampling algorithm with inexpensive early rejection and acceptance steps. But in HiER-leap, large portions of intra-block sampling may be done in parallel. An accept/reject step is used to synchronize across blocks. This method scales well when many reaction channels are present and has desirable asymptotic properties. The algorithm is exact, parallelizable and achieves a significant speedup over the stochastic simulation algorithm and ER-leap on certain problems. This algorithm offers a potentially important step towards efficient in silico modeling of entire organisms.

The Role of Endoplasmic Reticulum Stress in Human Pathology

PubMed Central

Oakes, Scott A.; Papa, Feroz R.

2017-01-01

Numerous genetic and environmental insults impede the ability of cells to properly fold and posttranslationally modify secretory and transmembrane proteins in the endoplasmic reticulum (ER), leading to a buildup of misfolded proteins in this organelle—a condition called ER stress. ER-stressed cells must rapidly restore protein-folding capacity to match protein-folding demand if they are to survive. In the presence of high levels of misfolded proteins in the ER, an intracellular signaling pathway called the unfolded protein response (UPR) induces a set of transcriptional and translational events that restore ER homeostasis. However, if ER stress persists chronically at high levels, a terminal UPR program ensures that cells commit to self-destruction. Chronic ER stress and defects in UPR signaling are emerging as key contributors to a growing list of human diseases, including diabetes, neurodegeneration, and cancer. Hence, there is much interest in targeting components of the UPR as a therapeutic strategy to combat these ER stress–associated pathologies. PMID:25387057

Unfolded Protein Response of the Endoplasmic Reticulum in Tumor Progression and Immunogenicity

PubMed Central

Yoo, Yoon Seon; Han, Hye Gyeong

2017-01-01

The endoplasmic reticulum (ER) is a pivotal regulator of folding, quality control, trafficking, and targeting of secreted and transmembrane proteins, and accordingly, eukaryotic cells have evolved specialized machinery to ensure that the ER enables these proteins to acquire adequate folding and maturation in the presence of intrinsic and extrinsic insults. This adaptive capacity of the ER to intrinsic and extrinsic perturbations is important for maintaining protein homeostasis, which is termed proteostasis. Failure in adaptation to these perturbations leads to accumulation of misfolded or unassembled proteins in the ER, which is termed ER stress, resulting in the activation of unfolded protein response (UPR) of the ER and the execution of ER-associated degradation (ERAD) to restore homeostasis. Furthermore, both of the two axes play key roles in the control of tumor progression, inflammation, immunity, and aging. Therefore, understanding UPR of the ER and subsequent ERAD will provide new insights into the pathogenesis of many human diseases and contribute to therapeutic intervention in these diseases. PMID:29430279

The Endoplasmic Reticulum Membrane Is Permeable to Small Molecules

PubMed Central

Le Gall, Sylvie; Neuhof, Andrea; Rapoport, Tom

2004-01-01

The lumen of the endoplasmic reticulum (ER) differs from the cytosol in its content of ions and other small molecules, but it is unclear whether the ER membrane is as impermeable as other membranes in the cell. Here, we have tested the permeability of the ER membrane to small, nonphysiological molecules. We report that isolated ER vesicles allow different chemical modification reagents to pass from the outside into the lumen with little hindrance. In permeabilized cells, the ER membrane allows the passage of a small, charged modification reagent that is unable to cross the plasma membrane or the lysosomal and trans-Golgi membranes. A larger polar reagent of ∼5 kDa is unable to pass through the ER membrane. Permeation of the small molecules is passive because it occurs at low temperature in the absence of energy. These data indicate that the ER membrane is significantly more leaky than other cellular membranes, a property that may be required for protein folding and other functions of the ER. PMID:14617815

Repertoires of emotion regulation: A person-centered approach to assessing emotion regulation strategies and links to psychopathology.

PubMed

Dixon-Gordon, Katherine L; Aldao, Amelia; De Los Reyes, Andres

2015-01-01

Despite growing research on emotion regulation (ER) strategies and psychopathology, research has primarily focused on identifying one-to-one associations between ER strategies and symptoms. Thus, little is known about how patterns in the repertoires of ER strategies are associated with different mental disorders. We utilised latent class analysis to identify distinct repertoires of ER strategies, and their links with various psychopathology domains (i.e., anxiety, depression, disordered eating, borderline personality). Participants (N = 531) reported on their use of seven ER strategies in six recalled stressful contexts, as well as on their symptoms of psychopathology. We identified five classes of ER strategies: Low Regulators (n = 168), High Regulators (n = 140), Adaptive Regulators (n = 99), Worriers/Ruminators (n = 96) and Avoiders (n = 28). Generally, High Regulators and Worriers/Ruminators endorsed greater levels of psychopathology, relative to Low and Adaptive Regulators. Our findings underscore the importance of characterising the dynamics of ER repertoires when seeking to understand links between ER strategies and psychopathology.

The clinical effectiveness and cost-effectiveness of exercise referral schemes: a systematic review and economic evaluation.

PubMed

Pavey, T G; Anokye, N; Taylor, A H; Trueman, P; Moxham, T; Fox, K R; Hillsdon, M; Green, C; Campbell, J L; Foster, C; Mutrie, N; Searle, J; Taylor, R S

2011-12-01

Exercise referral schemes (ERS) aim to identify inactive adults in the primary-care setting. The GP or health-care professional then refers the patient to a third-party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the individual. To assess the clinical effectiveness and cost-effectiveness of ERS for people with a diagnosed medical condition known to benefit from physical activity (PA). The scope of this report was broadened to consider individuals without a diagnosed condition who are sedentary. MEDLINE; EMBASE; PsycINFO; The Cochrane Library, ISI Web of Science; SPORTDiscus and ongoing trial registries were searched (from 1990 to October 2009) and included study references were checked. Systematic reviews: the effectiveness of ERS, predictors of ERS uptake and adherence, and the cost-effectiveness of ERS; and the development of a decision-analytic economic model to assess cost-effectiveness of ERS. Seven randomised controlled trials (UK, n = 5; non-UK, n = 2) met the effectiveness inclusion criteria, five comparing ERS with usual care, two compared ERS with an alternative PA intervention, and one to an ERS plus a self-determination theory (SDT) intervention. In intention-to-treat analysis, compared with usual care, there was weak evidence of an increase in the number of ERS participants who achieved a self-reported 90-150 minutes of at least moderate-intensity PA per week at 6-12 months' follow-up [pooled relative risk (RR) 1.11, 95% confidence interval 0.99 to 1.25]. There was no consistent evidence of a difference between ERS and usual care in the duration of moderate/vigorous intensity and total PA or other outcomes, for example physical fitness, serum lipids, health-related quality of life (HRQoL). There was no between-group difference in outcomes between ERS and alternative PA interventions or ERS plus a SDT intervention. None of the included trials separately reported outcomes in individuals with medical diagnoses. Fourteen observational studies and five randomised controlled trials provided a numerical assessment of ERS uptake and adherence (UK, n = 16; non-UK, n = 3). Women and older people were more likely to take up ERS but women, when compared with men, were less likely to adhere. The four previous economic evaluations identified suggest ERS to be a cost-effective intervention. Indicative incremental cost per quality-adjusted life-year (QALY) estimates for ERS for various scenarios were based on a de novo model-based economic evaluation. Compared with usual care, the mean incremental cost for ERS was £169 and the mean incremental QALY was 0.008, with the base-case incremental cost-effectiveness ratio at £20,876 per QALY in sedentary people without a medical condition and a cost per QALY of £14,618 in sedentary obese individuals, £12,834 in sedentary hypertensive patients, and £8414 for sedentary individuals with depression. Estimates of cost-effectiveness were highly sensitive to plausible variations in the RR for change in PA and cost of ERS. We found very limited evidence of the effectiveness of ERS. The estimates of the cost-effectiveness of ERS are based on a simple analytical framework. The economic evaluation reports small differences in costs and effects, and findings highlight the wide range of uncertainty associated with the estimates of effectiveness and the impact of effectiveness on HRQoL. No data were identified as part of the effectiveness review to allow for adjustment of the effect of ERS in different populations. There remains considerable uncertainty as to the effectiveness of ERS for increasing activity, fitness or health indicators or whether they are an efficient use of resources in sedentary people without a medical diagnosis. We failed to identify any trial-based evidence of the effectiveness of ERS in those with a medical diagnosis. Future work should include randomised controlled trials assessing the cinical effectiveness and cost-effectivenesss of ERS in disease groups that may benefit from PA. The National Institute for Health Research Health Technology Assessment programme.

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

PubMed

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

PubMed

Siddiq, Afshan; Couch, Fergus J; Chen, Gary K; Lindström, Sara; Eccles, Diana; Millikan, Robert C; Michailidou, Kyriaki; Stram, Daniel O; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M; Buring, Julie E; Buys, Saundra S; Campa, Daniele; Carpenter, Jane E; Chasman, Daniel I; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S; Czene, Kamila; Deming, Sandra L; Diasio, Robert B; Diver, W Ryan; Dunning, Alison M; Durcan, Lorraine; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M; Gerty, Susan M; Rodriguez-Gil, Jorge L; Giles, Graham G; van Gils, Carla H; Godwin, Andrew K; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N; Hopper, John L; Hu, Jennifer J; Huntsman, Scott; Ingles, Sue A; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B; John, Esther M; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N; Coetzee, Gerhard A; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G; McLean, Catriona A; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R; Montgomery, Grant W; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J; Palmer, Julie R; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F; Schmutzler, Rita K; Slager, Susan; Southey, Melissa C; Stevens, Kristen N; Sinn, Hans-Peter; Press, Michael F; Ross, Eric; Riboli, Elio; Ridker, Paul M; Schumacher, Fredrick R; Severi, Gianluca; Dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J; Thun, Michael J; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F; Hunter, David J; Henderson, Brian E; Chanock, Stephen J; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A; Vachon, Celine M

2012-12-15

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

PubMed Central

Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

2012-01-01

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. PMID:22976474

Estrogen receptor accessory proteins augment receptor-DNA interaction and DNA bending.

PubMed

Landel, C C; Potthoff, S J; Nardulli, A M; Kushner, P J; Greene, G L

1997-01-01

Increasing evidence suggests that accessory proteins play an important role in the ability of the estrogen receptor (ER) and other nuclear hormone receptors to modulate transcription when bound to cis-acting hormone response elements in target genes. We have previously shown that four proteins, hsp70, protein disulfide isomerase (PDI) and two unknown proteins (p48 and p45), copurify with ER that has been isolated by site-specific DNA chromatography (BERE) and influence the interaction of ER with DNA in vitro. To better define the nature of these effects, we used filter binding and electrophoretic mobility shift assays to study the ability of these proteins to alter the kinetics of ER-DNA interaction and to influence the ability of ER to bend DNA when bound to an estrogen response element (ERE). The results of both assays indicate that ERE-purified ER, with its four associated proteins (hsp70, PDI, p48, p45), has a greater ability to bind to the vitellogenin A2 ERE than ER purified by estradiol-Sepharose chromatography in the absence (ESeph) or presence (EATP) of ATP, in which p48, p45 (ESeph) and hsp70 (EATP) are removed. Surprisingly, the rates of association and dissociation of ER and ERE were essentially the same for all three mixtures, suggesting that one or more ER-associated proteins, especially p45 and p48, may be required for ER to attain maximum DNA binding activity. In addition, circular permutation and phasing analyses demonstrated that the same ER-associated proteins produced higher order ER-DNA complexes that significantly increased the magnitude of DNA distortion, but did not alter the direction of the ER-induced bend of ERE-containing DNA fragments, which was toward the major groove of the DNA helix. These results suggest that p45 and/or p48 and possibly hsp70, play an important role both in the specific DNA binding and bending activities of ER and thus contribute to the overall stimulation of transcription in target genes that contain cis-acting EREs.

Inhibition of endoplasmic reticulum stress improves coronary artery function in type 2 diabetic mice.

PubMed

Choi, Soo-Kyoung; Lim, Mihwa; Yeon, Soo-In; Lee, Young-Ho

2016-06-01

What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, the role of exacerbated ER stress in vascular dysfunction in type 2 diabetes remains unknown. What is the main finding and its importance? The main findings of this study are that ER stress is increased in the coronary arteries in type 2 diabetes, and inhibition of ER stress using taurine-conjugated ursodeoxycholic acid improves vascular function, which is associated with normalization of the myogenic response and endothelium-dependent relaxation. Vascular dysfunction is a major complication in type 2 diabetes. Although endoplasmic reticulum (ER) stress has been suggested to be a contributory factor in cardiovascular diseases, the relationship between ER stress and vascular dysfunction in type 2 diabetes remains unclear. Thus, in the present study, we examined whether ER stress contributes to coronary artery dysfunction and whether inhibition of ER stress ameliorates vascular function in type 2 diabetes. Type 2 diabetic mice and their control counterparts were treated with an ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, 150 mg kg(-1)  day(-1) , by i.p. injection) for 2 weeks or not treated. The myogenic response and endothelium-dependent relaxation were measured in pressurized coronary arteries. In type 2 diabetic mice, blood glucose and body weight were elevated compared with control mice. The myogenic response was potentiated and endothelium-dependent relaxation impaired in coronary arteries from the type 2 diabetic mice. Interestingly, treatment with the ER stress inhibitor normalized the myogenic responses and endothelium-dependent relaxation. These data were associated with an increase in ER stress marker expression or phosphorylation (IRE1-XBP-1 and PERK-eIF2α) in type 2 diabetic mice, which were reduced by treatment with the ER stress inhibitor. Inhibition of ER stress normalizes the myogenic response and improves vascular function in type 2 diabetes. Therefore, ER stress could be a potential target for cardiovascular diseases in diabetes mellitus. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.