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Sample records for raske overvaegtige er

  1. Somatic Activation of rasK Gene in a Human Ovarian Carcinoma

    NASA Astrophysics Data System (ADS)

    Feig, L. A.; Bast, R. C.; Knapp, R. C.; Cooper, G. M.

    1984-02-01

    A tumor isolate from a patient with serous cystadenocarcinoma of the ovary contained an activated rasK gene detected by transfection of NIH/3T3 cells. In contrast, DNA from normal cells of the same patient lacked transforming activity, indicating that activation of this transforming gene was the consequence of somatic mutation in the neoplastic cells. The transforming gene product displayed an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels that differed from the mobilities of rasK transforming proteins in other tumors, indicating that a previously undescribed mutation was responsible for activation of rasK in this ovarian carcinoma.

  2. ER Stress and Autophagy.

    PubMed

    Lee, W-S; Yoo, W-H; Chae, H-J

    2015-01-01

    Eukaryotic cells respond to various types of stresses caused by changes in the extracellular environment. Intracellular factors, such as the accumulation of misfolded proteins in the endoplasmic reticulum (ER), also cause stress and activate the unfolded protein response (UPR), which induces the expression of chaperones and proteins involved in the recovery process. However, if the stress is excessive or sustained, and ER function cannot be restored, the UPR triggers apoptosis, thereby removing the affected cell. It is now apparent that ER stress is also a potent trigger for autophagy, a self-degradative process that has an adaptive function. This review surveys the intersection of ER stress and autophagy and highlights the potential therapeutic implications thereof. PMID:26391548

  3. ER-2 in flight

    NASA Technical Reports Server (NTRS)

    1996-01-01

    In this film clip, we see an ER-2 on its take off roll and climb as it departs from runway 22 at Edwards AFB, California. In 1981, NASA acquired its first ER-2 aircraft. The agency obtained a second ER-2 in 1989. These airplanes replaced two Lockheed U-2 aircraft, which NASA had used to collect scientific data since 1971. The U-2, and later the ER-2, were based at the Ames Research Center, Moffett Field, California, until 1997. In 1997, the ER-2 aircraft and their operations moved to NASA Dryden Flight Research Center, Edwards, California. Since the inaugural flight for this program, August 31, 1971, NASA U-2 and ER-2 aircraft have flown more than 4,000 data missions and test flights in support of scientific research conducted by scientists from NASA, other federal agencies, states, universities, and the private sector. NASA is currently using two ER-2 Airborne Science aircraft as flying laboratories. The aircraft, based at NASA Dryden, collect information about our surroundings, including Earth resources, celestial observations, atmospheric chemistry and dynamics, and oceanic processes. The aircraft also are used for electronic sensor research and development, satellite calibration, and satellite data validation. The ER-2 is a versatile aircraft well-suited to perform multiple mission tasks. It is 30 percent larger than the U-2 with a 20 feet longer wingspan and a considerably increased payload over the older airframe. The aircraft has four large pressurized experiment compartments and a high-capacity AC/DC electrical system, permitting it to carry a variety of payloads on a single mission. The modular design of the aircraft permits rapid installation or removal of payloads to meet changing mission requirements. The ER-2 has a range beyond 3,000 miles (4800 kilometers); is capable of long flight duration and can operate at altitudes up to 70,000 feet (21.3 kilometers) if required. Operating at an altitude of 65,000 feet (19.8 kilometers) the ER-2 acquires data above 95 percent of the Earth's atmosphere. At this altitude the aircraft provides a stable platform for Earth imagery, atmospheric research, and electronic sensor development. Because the ER-2 can fly so high, its sensors 'mimic' sensors carried aboard orbiting satellites. For most missions the ER-2 operates at altitudes between 65,000 feet and 70,000 feet. Depending on aircraft weight, the ER-2 reaches a cruise altitude of 65,000 feet within 20 minutes. Typical cruise speed is 410 knots. The range for a normal 6-hour mission is 2,200 nautical miles (4,070 kilometers), which yields 5 hours of data collection at high altitude. The aircraft is capable of longer missions of up to 8 hours and ranges of up to 3,000 nautical miles (5,500 kilometers). The ER-2 can carry a maximum payload of 2,600 pounds (1,179 kilograms) distributed in the equipment bay, nose area, and wing pods. In 1991, NASA launched a comprehensive program to study the Earth as an environmental system, now called the Earth Science Enterprise. By using satellites and other tools like the ER-2 to intensively study the Earth, NASA hopes to expand human understanding of how natural processes affect people and how people might be affecting them. Such studies will yield improved weather forecasts, tools for managing agriculture and forests, information for fishermen and local planners, and, eventually, the ability to predict how the climate will change in the future. NASA ER-2 aircraft have played an important role in Earth Science research, like studying ozone depletion over Antarctica and the Arctic. In August and September 1987 an ER-2 traveled to Punta Arenas, Chile, to conduct overflights of the Antarctic. Results from this study provided information suggesting that human-made chemical compounds, specifically chloro-fluorocarbons, caused enormous ozone depletion over the Antarctic region. Subsequent deployments have continued the study of the production and loss of ozone in the polar stratosphere. Atmospheric experiments were flown from Stavanger, Norway in January and February 1989 north of the Arctic Circle to investigate ozone loss in the stratosphere. From October 1991 through October 1994 a series of ER-2 flights were flown out of Fairbanks, Alaska; Bangor, Maine; and Christchurch, New Zealand to study the winter polar stratosphere. During these polar campaigns the ER-2 acquired atmospheric data with an array of up to 18 sampling instruments onboard the aircraft. Other atmospheric experiments provided more information about clouds and radiation that will help improve climate models. These experiments coordinated satellite, airborne, and surface observations to investigate how cloud formation affects global temperatures. Recently the ER-2, team conducted missions to help determine the effects of a proposed fleet of high-altitude, high-speed transport aircraft. Background measurements of chemistry at high altitudes have been compared to measurements of exhaust plumes of high altitude aircraft like the Concorde and the ER-2. A series of flights from April to September 1997 originating in Fairbanks, Alaska, resulted in the first in situ study of summer ozone conditions in a polar region. Since the program's inception, the NASA U-2's and ER-2's assisted in developing satellite sensors by testing sensor prototypes or by simulating proposed configurations with existing systems. In the early years of the program the U-2 flew prototypes of the Thematic Mapper and the Multispectral Scanner now operating on Landsats 4 and 5.

  4. ER-2 in flight

    NASA Technical Reports Server (NTRS)

    1996-01-01

    In this film clip, we see an ER-2 on its take off roll and climb as it departs from runway 22 at Edwards AFB, California. In 1981, NASA acquired its first ER-2 aircraft. The agency obtained a second ER-2 in 1989. These airplanes replaced two Lockheed U-2 aircraft, which NASA had used to collect scientific data since 1971. The U-2, and later the ER-2, were based at the Ames Research Center, Moffett Field, California, until 1997. In 1997, the ER-2 aircraft and their operations moved to NASA Dryden Flight Research Center, Edwards, California. Since the inaugural flight for this program, August 31, 1971, NASA U-2 and ER-2 aircraft have flown more than 4,000 data missions and test flights in support of scientific research conducted by scientists from NASA, other federal agencies, states, universities, and the private sector. NASA is currently using two ER-2 Airborne Science aircraft as flying laboratories. The aircraft, based at NASA Dryden, collect information about our surroundings, including Earth resources, celestial observations, atmospheric chemistry and dynamics, and oceanic processes. The aircraft also are used for electronic sensor research and development, satellite calibration, and satellite data validation. The ER-2 is a versatile aircraft well-suited to perform multiple mission tasks. It is 30 percent larger than the U-2 with a 20 feet longer wingspan and a considerably increased payload over the older airframe. The aircraft has four large pressurized experiment compartments and a high-capacity AC/DC electrical system, permitting it to carry a variety of payloads on a single mission. The modular design of the aircraft permits rapid installation or removal of payloads to meet changing mission requirements. The ER-2 has a range beyond 3,000 miles (4800 kilometers); is capable of long flight duration and can operate at altitudes up to 70,000 feet (21.3 kilometers) if required. Operating at an altitude of 65,000 feet (19.8 kilometers) the ER-2 acquires data above 95 percent of the Earth's atmosphere. At this altitude the aircraft provides a stable platform for Earth imagery, atmospheric research, and electronic sensor development. Because the ER-2 can fly so high, its sensors 'mimic' sensors carried aboard orbiting satellites. For most missions the ER-2 operates at altitudes between 65,000 feet and 70,000 feet. Depending on aircraft weight, the ER-2 reaches a cruise altitude of 65,000 feet within 20 minutes. Typical cruise speed is 410 knots. The range for a normal 6-hour mission is 2,200 nautical miles (4,070 kilometers), which yields 5 hours of data collection at high altitude. The aircraft is capable of longer missions of up to 8 hours and ranges of up to 3,000 nautical miles (5,500 kilometers). The ER-2 can carry a maximum payload of 2,600 pounds (1,179 kilograms) distributed in the equipment bay, nose area, and wing pods. In 1991, NASA launched a comprehensive program to study the Earth as an environmental system, now called the Earth Science Enterprise. By using satellites and other tools like the ER-2 to intensively study the Earth, NASA hopes to expand human understanding of how natural processes affect people and how people might be affecting them. Such studies will yield improved weather forecasts, tools for managing agriculture and forests, information for fishermen and local planners, and, eventually, the ability to predict how the climate will change in the future. NASA ER-2 aircraft have played an important role in Earth Science research, like studying ozone depletion over Antarctica and the Arctic. In August and September 1987 an ER-2 traveled to Punta Arenas, Chile, to conduct overflights of the Antarctic. Results from this study provided information suggesting that human-made chemical compounds, specifically chloro-fluorocarbons, caused enormous ozone depletion over the Antarctic region. Subsequent deployments have continued the study of the production and loss of ozone in the polar stratosphere. Atmospheric experiments were flown from Stavanger, Norway in January and February 1989 north of the Arcti

  5. Estrogen receptor (ER)-? isoforms: A key to understanding ER-? signaling

    PubMed Central

    Leung, Yuet-Kin; Mak, Paul; Hassan, Sazzad; Ho, Shuk-Mei

    2006-01-01

    Estrogen receptor beta (ER-?) regulates diverse physiological functions in the human body. Current studies are confined to ER-?1, and the functional roles of isoforms 2, 4, and 5 remain unclear. Full-length ER-?4 and -?5 isoforms were obtained from a prostate cell line, and they exhibit differential expression in a wide variety of human tissues/cell lines. Through molecular modeling, we established that only ER-?1 has a full-length helix 11 and a helix 12 that assumes an agonist-directed position. In ER-?2, the shortened C terminus results in a disoriented helix 12 and marked shrinkage in the coactivator binding cleft. ER-?4 and -?5 completely lack helix 12. We further demonstrated that ER-?1 is the only fully functional isoform, whereas ER-?2, -?4, and -?5 do not form homodimers and have no innate activities of their own. However, the isoforms can heterodimerize with ER-?1 and enhance its transactivation in a ligand-dependent manner. ER-?1 tends to form heterodimers with other isoforms under the stimulation of estrogens but not phytoestrogens. Collectively, these data support the premise that (i) ER-?1 is the obligatory partner of an ER-? dimer, whereas the other isoforms function as variable dimer partners with enhancer activity, and (ii) a single functional helix 12 in a dimer is sufficient for gene transactivation. Thus, ER-? behaves like a noncanonical type-I receptor, and its action may depend on differential amounts of ER-?1 homo- and heterodimers formed upon stimulation by a specific ligand. Our findings have provided previously unrecognized directions for studying ER-? signaling and design of ER-?-based therapies. PMID:16938840

  6. Reciprocal Regulation of ER? and ER? Stability and Activity by Diptoindonesin G.

    PubMed

    Zhao, Zibo; Wang, Lu; James, Taryn; Jung, Youngeun; Kim, Ikyon; Tan, Renxiang; Hoffmann, F Michael; Xu, Wei

    2015-12-17

    ER? is regarded as a "tumor suppressor" in breast cancer due to its anti-proliferative effects. However, unlike ER?, ER? has not been developed as a therapeutic target in breast cancer due to loss of ER? inaggressive cancers. In a small-molecule library screen for ER? stabilizers, we identified Diptoindonesin G (Dip G), which significantly increases ER? protein stability while decreasing ER? protein levels. Dip G enhances the transcription and anti-proliferative activities of ER?, while attenuating the transcription and proliferative effects of ER?. Further investigation revealed that instead of targeting ER, Dip G targets the CHIP E3 ubiquitin ligase shared by ER? and ER?. Thus, Dip G is a dual-functional moiety that reciprocally controls ER? and ER? protein stability and activities via an indirect mechanism. The ER? stabilization effects of Dip G may enable the development of ER?-targeted therapies for human breast cancers. PMID:26670079

  7. Protein folding in the ER.

    SciTech Connect

    Stevens, F. J.; Argon, Y.; Biosciences Division; Univ. of Chicago

    1999-10-01

    The endoplasmic reticulum (ER) is a major protein folding compartment for secreted, plasma membrane and organelle proteins. Each of these newly-synthesized polypeptides folds in a deterministic process, affected by the unique conditions that exist in the ER. An understanding of protein folding in the ER is a fundamental biomolecular challenge at two levels. The first level addresses how the amino acid sequence programs that polypeptide to efficiently arrive at a particular fold out of a multitude of alternatives, and how different sequences obtain similar folds. At the second level are the issues introduced by folding not in the cytosol, but in the ER, including the risk of aggregation in a molecularly crowded environment, accommodation of post-translational modifications and the compatibility with subsequent intracellular trafficking. This review discusses both the physicochemical and cell biological constraints of folding, which are the challenges that the ER molecular chaperones help overcome.

  8. ER stress and endothelial dysfunction

    PubMed Central

    Lenna, Stefania; Han, Rong; Trojanowska, Maria

    2014-01-01

    Prolonged perturbation of the endoplasmic reticulum (ER) leads to ER stress and unfolded protein response (UPR) and contributes to the pathogenesis of various chronic disorders. This review focuses on the role of ER stress and UPR in endothelial cells and the relevance of these processes to vascular diseases. Chronic activation of ER stress and UPR pathways in endothelial cells leads to increased oxidative stress and inflammation, and often results in cell death. Because endothelial cells play a pivotal role in maintaining vascular homeostasis, various pathological conditions interfering with this homeostasis including homocysteinemia, hyperlipidimia, high glucose, insulin resistance, disturbed blood flow, and oxidative stress can lead to endothelial dysfunction in part through the activation of ER stress. We discuss recently discovered aspects of the role of ER stress/UPR in those pathological conditions. We also summarize recent findings implicating ER stress and UPR in systemic hypertension, as well as pulmonary arterial hypertension (PAH). Finally, this review will highlight a novel role of UPR mediators in the process of angiogenesis. PMID:25130181

  9. FIRE_MS_ER2_LIDAR

    Atmospheric Science Data Center

    2015-11-25

    FIRE_MS_ER2_LIDAR Project Title: FIRE I - Marine Stratocumulus ... Aircraft, NASA ER2 Instrument: LIDAR Spatial Coverage: (30.30, 39.86) (-124.97, -118.37) ... Search Guide Documents: ER-2 LIDAR Data Set Guide Readme Files: Readme ER-2 LIDAR ...

  10. The Effectiveness of Core ER Principles

    ERIC Educational Resources Information Center

    Jeon, Eun-Young; Day, Richard R.

    2015-01-01

    This discussion piece continues the discussion forum on extensive reading (ER) from the April 2015 issue of "Reading in a Foreign Language." In that forum, a number of the discussions were concerned with the principles of ER (Day & Bamford, 2002) in implementing ER. Our discussion also concerns the principles; we examine ER programs

  11. ERS-1 SAR data processing

    NASA Technical Reports Server (NTRS)

    Leung, K.; Bicknell, T.; Vines, K.

    1986-01-01

    To take full advantage of the synthetic aperature radar (SAR) to be flown on board the European Space Agency's Remote Sensing Satellite (ERS-1) (1989) and the Canadian Radarsat (1990), the implementation of a receiving station in Alaska is being studied to gather and process SAR data pertaining in particular to regions within the station's range of reception. The current SAR data processing requirement is estimated to be on the order of 5 minutes per day. The Interim Digital Sar Processor (IDP) which was under continual development through Seasat (1978) and SIR-B (1984) can process slightly more than 2 minutes of ERS-1 data per day. On the other hand, the Advanced Digital SAR Processore (ADSP), currently under development for the Shuttle Imaging Radar C (SIR-C, 1988) and the Venus Radar Mapper, (VMR, 1988), is capable of processing ERS-1 SAR data at a real time rate. To better suit the anticipated ERS-1 SAR data processing requirement, both a modified IDP and an ADSP derivative are being examined. For the modified IDP, a pipelined architecture is proposed for the mini-computer plus array processor arrangement to improve throughout. For the ADSP derivative, a simplified version is proposed to enhance ease of implementation and maintainability while maintaing real time throughput rates. These processing systems are discussed and evaluated.

  12. Two-quasiparticle structures and isomers in {sup 168}Er, {sup 170}Er, and {sup 172}Er.

    SciTech Connect

    Dracoulis, G. D.; Lane, G. J.; Kondev, F. G.; Watanabe, H.; Seweryniak, D.; Zhu, S.; Carpenter, M. P.; Chiara, C. J.; Janssens, R. V. F.; Lauritsen, T.; Lister, C. J.; McCutchan, E. A.; Stefanescu, I.; Australian National Univ.; RIKEN; Univ. of Maryland

    2010-05-01

    The stable and neutron-rich isotopes 168Er, 170Er, and 172Er have been studied with Gammasphere using inelastic excitation with energetic 136Xe beams. The previously assigned structures based on the proposed K?=4- isomeric intrinsic states in both 168Er and 170Er have been re-evaluated and an equivalent band identified in 172Er. In 170Er, the identification of a K?=6- band with transitions close in energy to those of the 4- band leads to a modified interpretation, since the overlap would have compromised previous analyses. The gK-gR values for the 4- bands deduced from the in-band ?-ray intensities for the sequence of isotopes suggest a predominantly two-neutron configuration in 168Er, an equally mixed two-neutron, two-proton configuration in 170Er, and a two-proton configuration in 172Er. A comprehensive decay scheme for the previously proposed 6+ isomer in 172Er has also been established, as well as band structures built on this isomer that closely resemble the 6+ and 7- two-neutron structures known in the isotone 174Yb. The implied K hindrances are discussed. The main decay path of the 6+ isomer occurs through the newly identified 4- isomer. The measured lifetimes of the 4- and 6+ isomers in 172Er are 57(3) and 822(90) ns, respectively. Multiquasiparticle calculations support the suggested configuration changes across the isotopic chain.

  13. ER morphology: sculpting with XendoU.

    PubMed

    Zhao, Guohua; Blackstone, Craig

    2014-12-15

    Endoplasmic reticulum (ER) sheet membranes are covered with ribosomes and RNAs that are involved in protein synthesis. A new study reveals that a calcium-activated endoribonuclease of the EndoU protein family promotes the formation of tubular ER networks, contributing to dynamic shaping of the ER in cells. PMID:25514011

  14. NASA ER-2: Flying Laboratory for Earth Science Studies

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    This viewgraph presentation gives an overview of the NASA ER-2 aircraft. The contents include: 1) ER-2 Specifications; 2) ER-2 Basic Configuration; 3) ER-2 Payload Areas: Nose Area; 4) ER-2 Payload Areas: SuperPod Fore and Aftbody; 5) ER-2 Payload Areas: SuperPod Midbody; 6) ER-2 Payload Areas: Q-Bay; 7) ER-2 Payload Areas: Q-Bay Hatch Designs; 8) ER-2 Payload Areas: External Pods; 9) ER-2 Electrical/Control Interface; 10) ER-2 Typical Flight Profile; 11) Tropical Composition, Cloud and Climate Coupling TC-4; 12) TC-4 Timeline; 13) TC4 Area of Interest; 14) ER-2 TC4 Payload; 15) A/C ready for fuel; 16) ER-2 Pilot being suited; 17) ER-2 Taxing; 18) ER-2 Pilot post flight debrief; and 19) NASA ER-2: Flying Laboratory for Earth Science Studies and Remote Sensing.

  15. Tank 241-ER-311, grab samples, ER311-98-1, ER311-98-2, ER311-98-3 analytical results for the final report

    SciTech Connect

    FULLER, R.K.

    1999-02-24

    This document is the final report for catch tank 241-ER-311 grab samples. Three grab samples ER311-98-1, ER311-98-2 and ER311-98-3 were taken from East riser of tank 241-ER-311 on August 4, 1998 and received by the 222-S Laboratory on August 4, 1998. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1998)and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Mulkey and Miller, 1997). The analytical results are presented in the data summary report (Table 1). No notification limits were exceeded.

  16. ER stress-induced cell death mechanisms.

    PubMed

    Sano, Renata; Reed, John C

    2013-12-01

    The endoplasmic-reticulum (ER) stress response constitutes a cellular process that is triggered by a variety of conditions that disturb folding of proteins in the ER. Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Here, we summarize recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease. This article is part of a Special Section entitled: Cell Death Pathways. PMID:23850759

  17. ER stress-induced cell death mechanisms

    PubMed Central

    Sano, Renata; Reed, John C.

    2013-01-01

    The endoplasmic-reticulum (ER) stress response constitutes a cellular process that is triggered by a variety of conditions that disturb folding of proteins in the ER. Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Here, we summarize recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease. PMID:23850759

  18. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    PubMed Central

    Bravo, Roberto; Gutierrez, Toms; Paredes, Felipe; Gatica, Damin; 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 ERmitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  19. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics.

    PubMed

    Bravo, Roberto; Gutierrez, Toms; Paredes, Felipe; Gatica, Damin; Rodriguez, Andrea E; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F G; Rothermel, Beverly A; Lavandero, Sergio

    2012-01-01

    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

  20. Cell proliferation and modulation of interaction of estrogen receptors with coregulators induced by ER? and ER? agonists.

    PubMed

    Evers, Nynke M; van den Berg, Johannes H J; Wang, Si; Melchers, Diana; Houtman, Ren; de Haan, Laura H J; Ederveen, Antwan G H; Groten, John P; Rietjens, Ivonne M C M

    2014-09-01

    The aim of the present study was to investigate modulation of the interaction of the ER? and ER? with coregulators in the ligand responses induced by estrogenic compounds. To this end, selective ER? and ER? agonists were characterized for intrinsic relative potency reflected by EC50 and maximal efficacy towards ER? and ER? mediated response in ER selective reporter gene assays, and subsequently tested for induction of cell proliferation in T47D-ER? cells with variable ER?/ER? ratio, and finally for ligand dependent modulation of the interaction of ER? and ER? with coregulators using the MARCoNI assay, with 154 unique nuclear receptor coregulator peptides derived from 66 different coregulators. Results obtained reveal an important influence of the ER?/ER? ratio and receptor selectivity of the compounds tested on induction of cell proliferation. ER? agonists activate cell proliferation whereas ER? suppresses ER? mediated cell proliferation. The responses in the MARCoNI assay reveal that upon ER? or ER? activation by a specific agonist, the modulation of the interaction of the ERs with coregulators is very similar indicating only a limited number of differences upon ER? or ER? activation by a specific ligand. Differences in the modulation of the interaction of the ERs with coregulators between the different agonists were more pronounced. Based on ligand dependent differences in the modulation of the interaction of the ERs with coregulators, the MARCoNI assay was shown to be able to classify the ER agonists discriminating between different agonists for the same receptor, a characteristic not defined by the ER selective reporter gene or proliferation assays. It is concluded that the ultimate effect of the model compounds on proliferation of estrogen responsive cells depends on the intrinsic relative potency of the agonist towards ER? and ER? and the cellular ER?/ER? ratio whereas differences in the modulation of the interaction of the ER? and ER? with coregulators contribute to the ligand dependent responses induced by estrogenic compounds. PMID:24923734

  1. Cell signaling events differentiate ER-negative subtypes from ER-positive breast cancer.

    PubMed

    Worsham, Maria J; Chitale, Dhanajay; Chen, Kang Mei; Datta, Indrani; Divine, George

    2015-05-01

    Currently available markers routinely used in clinical practice are of limited value to patients with estrogen receptor-negative (ER(-)) breast cancer [basal-like and HER2neu-positive (HER(+))], an aggressive subtype. Our aim was to uncover molecular pathways and signaling networks exposed by differentially methylated genes informative of the biology of ER(-) breast cancer (BC) subtypes versus ER-positive (ER(+)). Whole-genome methylation array analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip on 14 primary BC: five ER(+), four triple-negative (TNBC), and five ER(-)HER2(+). Degree of methylation was calculated as a ?-value (ranging from 0 to 1), and M-values [log (?/(1 - ?)] were used for significance tests. To identify methylated genes associated with ER(-) subtypes (TNBC and ER(-)HER2(+)) and distinct from ER(+), a weighted algorithm, developed to increase statistical rigor, called out genes in which methylation changed dramatically between ER(+) and ER(-) subtypes. Differentially methylated gene lists examined using Ingenuity Pathway Analysis called out canonical pathways and networks with clues to biological distinctiveness as well as relatedness between ER(-) subtypes as compared to ER(+) BC. The study highlights the interplay of ER(-) subtype-specific genes and their signaling pathways as potential putative fingerprints in refining classification of BC subtypes and as potential biological markers designed to hit multiple targets. PMID:25805566

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

    SciTech Connect

    Narang, V.; Seehra, M. S.; 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?K300?K) of the magnetization M at a fixed magnetic 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.

  3. Two-quasiparticle structures and isomers in {sup 168}Er, {sup 170}Er, and {sup 172}Er

    SciTech Connect

    Dracoulis, G. D.; Lane, G. J.; Kondev, F. G.; Chiara, C. J.; Watanabe, H.; Seweryniak, D.; Zhu, S.; Carpenter, M. P.; Janssens, R. V. F.; Lauritsen, T.; Lister, C. J.; McCutchan, E. A.; Stefanescu, I.

    2010-05-15

    The stable and neutron-rich isotopes {sup 168}Er, {sup 170}Er, and {sup 172}Er have been studied with Gammasphere using inelastic excitation with energetic {sup 136}Xe beams. The previously assigned structures based on the proposed K{sup p}i=4{sup -} isomeric intrinsic states in both {sup 168}Er and {sup 170}Er have been re-evaluated and an equivalent band identified in {sup 172}Er. In {sup 170}Er, the identification of a K{sup p}i=6{sup -} band with transitions close in energy to those of the 4{sup -} band leads to a modified interpretation, since the overlap would have compromised previous analyses. The g{sub K}-g{sub R} values for the 4{sup -} bands deduced from the in-band gamma-ray intensities for the sequence of isotopes suggest a predominantly two-neutron configuration in {sup 168}Er, an equally mixed two-neutron, two-proton configuration in {sup 170}Er, and a two-proton configuration in {sup 172}Er. A comprehensive decay scheme for the previously proposed 6{sup +} isomer in {sup 172}Er has also been established, as well as band structures built on this isomer that closely resemble the 6{sup +} and 7{sup -} two-neutron structures known in the isotone {sup 174}Yb. The implied K hindrances are discussed. The main decay path of the 6{sup +} isomer occurs through the newly identified 4{sup -} isomer. The measured lifetimes of the 4{sup -} and 6{sup +} isomers in {sup 172}Er are 57(3) and 822(90) ns, respectively. Multiquasiparticle calculations support the suggested configuration changes across the isotopic chain.

  4. ER Stress and Lipid Metabolism in Adipocytes

    PubMed Central

    Zha, Beth S.; Zhou, Huiping

    2012-01-01

    The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, ?-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance. PMID:22400114

  5. The cervical malignant cells display a down regulation of ER-? but retain the ER-? expression

    PubMed Central

    Lpez-Romero, Ricardo; Garrido-Guerrero, Efran; Rangel-Lpez, Anglica; Manuel-Apolinar, Leticia; Pia-Snchez, Patricia; Lazos-Ochoa, Minerva; Mantilla-Morales, Alejandra; Bandala, Cindy; Salcedo, Mauricio

    2013-01-01

    The human cervix is a tissue target of sex steroid hormones as estradiol (E2) which exerts its action through of the estrogen receptors alpha and beta (ER-? and ER-?). In this study we investigated the expression of ER-? and ER-? in human invasive cervical carcinomas using immunohistochemistry and RT-PCR analyses and compared with that observed in the corresponding normal tissue. The results show nuclear expression of ER-? mainly in the first third of normal cervical epithelium, however, decreased or absent expression were present in invasive cervical carcinoma, indicating that expression of ER-? is lost in cervical cancer. Nevertheless, by RT-PCR we were able to demonstrate mRNA expression of ER-? in invasive cervical tissues. These results suggest that loss of ER-? could be due to a mechanism of post-transcriptional and/or post-translational regulation of its gene during the progression to invasive carcinoma. On the other hand, ER-? was expressed in normal cervix with an expression pattern similar to ER-?. In addition to its nuclear localization, cytoplasmic immunoreaction of ER-? was present in the epithelium of invasive cervical carcinomas, suggesting an association between cytoplasmic ER-? expression and invasive phenotype in the cervical tumors. In summary, the results show that the cervical malignant cells tend to loss the ER-? but maintain the ER-? actively expressed. Loss of expression of ER-? in neoplastic tissue suggests that the estrogenic effects could be conducted through the ER-? in human neoplastic cervical tissue. More detailed studies are needed to confirm this suggestion and to determine the role of ER-? in cervical cancer. PMID:23923078

  6. Ternary Dy-Er-Al magnetic refrigerants

    DOEpatents

    Gschneidner, K.A. Jr.; Takeya, Hiroyuki

    1995-07-25

    A ternary magnetic refrigerant material comprising (Dy{sub 1{minus}x}Er{sub x})Al{sub 2} for a magnetic refrigerator using the Joule-Brayton thermodynamic cycle spanning a temperature range from about 60K to about 10K, which can be adjusted by changing the Dy to Er ratio of the refrigerant. 29 figs.

  7. Ternary Dy-Er-Al magnetic refrigerants

    DOEpatents

    Gschneidner, Jr., Karl A. (Ames, IA); Takeya, Hiroyuki (Ibaraki, JP)

    1995-07-25

    A ternary magnetic refrigerant material comprising (Dy.sub.1-x Er.sub.x)Al.sub.2 for a magnetic refrigerator using the Joule-Brayton thermodynamic cycle spanning a temperature range from about 60K to about 10K, which can be adjusted by changing the Dy to Er ratio of the refrigerant.

  8. BOREAS Level-0 ER-2 Aerial Photography

    NASA Technical Reports Server (NTRS)

    Newcomer, Jeffrey A.; Dominquez, Roseanne; Hall, Forrest G. (Editor)

    2000-01-01

    For BOReal Ecosystem-Atmosphere Study (BOREAS), the ER-2 and other aerial photography was collected to provide finely detailed and spatially extensive documentation of the condition of the primary study sites. The ER-2 aerial photography consists of color-IR transparencies collected during flights in 1994 and 1996 over the study areas.

  9. A screening cascade to identify ER? ligands.

    PubMed

    Filgueira, Carly S; Benod, Cindy; Lou, Xiaohua; Gunamalai, Prem S; Villagomez, Rosa A; Strom, Anders; Gustafsson, Jan-ke; Berkenstam, Anders L; Webb, Paul

    2014-01-01

    The establishment of effective high throughput screening cascades to identify nuclear receptor (NR) ligands that will trigger defined, therapeutically useful sets of NR activities is of considerable importance. Repositioning of existing approved drugs with known side effect profiles can provide advantages because de novo drug design suffers from high developmental failure rates and undesirable side effects which have dramatically increased costs. Ligands that target estrogen receptor ? (ER?) could be useful in a variety of diseases ranging from cancer to neurological to cardiovascular disorders. In this context, it is important to minimize cross-reactivity with ER?, which has been shown to trigger increased rates of several types of cancer. Because of high sequence similarities between the ligand binding domains of ER? and ER?, preferentially targeting one subtype can prove challenging. Here, we describe a sequential ligand screening approach comprised of complementary in-house assays to identify small molecules that are selective for ER?. Methods include differential scanning fluorimetry, fluorescence polarization and a GAL4 transactivation assay. We used this strategy to screen several commercially-available chemical libraries, identifying thirty ER? binders that were examined for their selectivity for ER? versus ER?, and tested the effects of selected ligands in a prostate cancer cell proliferation assay. We suggest that this approach could be used to rapidly identify candidates for drug repurposing. PMID:25422593

  10. Understanding microstructures of Er centers in impurity codoped Si:Er

    NASA Astrophysics Data System (ADS)

    Huang, Mengbing; Ren, Xiaotang; Das, Tara

    2002-03-01

    Doping Er into Si is a very attractive method for achieving optical integration on Si chips. It is known that codoped impurities (e.g., carbon, oxygen, nitrogen and fluorine) can greatly improve the luminescence properties of Er. However, the detailed mechanisms for codopant effects are still unclear, due to a lack of information on micro-structures of Er related luminescence centers. In this work, we examine modifications in lattice structures induced by codopants in Si:Er. The lattice locations of Er and codopants (C, N, O and F) are determined using ion channeling, and are correlated with the optical properties of Er atoms in Si. An interesting observation is that codopants in Si tend to relocate Er atoms from the tetrahedral to hexagonal site, with oxygen giving rise to the highest efficiency in Er site change. Our experiments have been performed for various concentrations of codopants and annealing temperatures, allowing us to determine the efficiency for different codopant species in changing Er lattice site (e.g., 1.5 carbon atoms needed for moving one Er out of the tetrahedral site), as well as the effective energy involved in the process. We compare these experimental results with previously proposed models for micro-structures of Er centers in Si.

  11. Er site in Er-implanted Si nanoclusters embedded in SiO{sub 2}

    SciTech Connect

    Maurizio, C.; D'Acapito, F.; Iacona, F.; Franzo, G.; Priolo, F.

    2006-11-15

    We have investigated by extended x-ray absorption fine structure spectroscopy the local order around Er atoms introduced by ion implantation in substoichiometric silica films prepared by plasma enhanced chemical vapor deposition, where Si nanoclusters have been formed by different preimplantation annealing processes. The results show that Er atoms are surrounded by a first shell of O atoms and no Er-Si direct correlations are observed; moreover, while the variation of the preimplantation annealing temperature has no effect on the Er site, it is observed that the increase of the Er concentration determines an increase of both the Er first shell coordination number and the Er-O interatomic distance, becoming more similar to those of Er{sub 2}O{sub 3}. In the presence of an extensive phase separation between Si and SiO{sub 2} the local environment around Er plays a crucial role on the efficiency of the photoluminescence emission at 1.54 {mu}m, which is significantly increased when the first shell of atoms around Er is closer to that one of Er{sub 2}O{sub 3}.

  12. The Phytoestrogen Genistein Affects Breast Cancer Cells Treatment Depending on the ER?/ER? Ratio.

    PubMed

    Pons, Daniel Gabriel; Nadal-Serrano, Mercedes; Torrens-Mas, Margalida; Oliver, Jordi; Roca, Pilar

    2016-01-01

    Genistein (GEN) is a phytoestrogen found in soybeans. GEN exerts its functions through its interaction with the estrogen receptors (ER), ER? and ER?, and we previously reported that the ER?/ER? ratio is an important factor to consider in GEN-treated breast cancer cells. The aim of this study was to investigate the effects of GEN in breast cancer cells with different ER?/ER? ratio: MCF-7 (high ratio), T47D (low ratio), and MCF-7 overexpressing ER? (MCF7?+?ER?) treated with cisplatin (CDDP), paclitaxel (PTX) or tamoxifen (TAM). Cell viability, ROS production, autophagy, apoptosis, antioxidant enzymes protein levels, and cell cycle were analyzed. GEN treatment provoked an increase in cell viability in MCF-7 cells and in the antioxidant enzymes protein levels in combination with the cytotoxic agents, decreasing ROS production (CDDP?+?GEN and TAM+GEN) and autophagy (TAM?+?GEN) or apoptosis (CDDP?+?GEN and TAM?+?GEN). Moreover GEN treatment enhanced the cell cycle S phase entry in CDDP+GEN- and TAM?+?GEN-treated MCF-7 cells and, in the case of CDDP?+?GEN, increased the proportion of cells in the G2/M phase and decreased it in the subG0 /G1 phase. Otherwise, in the T47D and MCF7?+?ER? cells the combination of GEN with cytotoxic treatments did not cause significant changes in these parameters, even TAM?+?GEN-treated T47D cells showed less cell viability due to an increment in the autophagy. In conclusion, GEN consumption may be counterproductive in those patients receiving anticancer treatment with a high ER?/ER? ratio diagnosed breast cancer and it could be harmless or even beneficial in those patients with a lower ER?/ER? ratio breast cancer cells. J. Cell. Biochem. 117: 218-229, 2016. 2015 Wiley Periodicals, Inc. PMID:26100284

  13. COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and ?-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 ?-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 ?-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 ?-cell death. Among the 4 components to maintain ER homeostasis in ?-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 ?-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 ?-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2? (p-eIF2?) 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 ?-cell survival. PMID:26083833

  14. The effect of glucuronidation on isoflavone induced estrogen receptor (ER)? and ER? mediated coregulator interactions.

    PubMed

    Beekmann, Karsten; de Haan, Laura H J; Actis-Goretta, Lucas; Houtman, Ren; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2015-11-01

    Non-prenylated isoflavone aglycones are known to have phyto-estrogenic properties and act as agonistic ligands on ER? and ER? due to their structural resemblance to 17?-estradiol (E2). Genistein and daidzein are the two main dietary isoflavones; upon uptake they are extensively metabolized and exist nearly exclusively as their conjugated forms in biological fluids. Little is known about the effect of conjugation on the intrinsic estrogenic activities of these isoflavones. To characterize and compare the intrinsic estrogenic activities of genistein and daidzein, and their respective 7-O-glucuronide metabolites a cell-free assay system was employed that determines the ligand-induced changes in ER?- and ER?-ligand binding domain (LBD) interactions with 154 different binding motifs derived from 66 different nuclear receptor coregulators. The glucuronides were 8 to 4400 times less potent than their respective aglycones to modulate ER?-LBD and ER?-LBD-coregulator interactions. Glucuronidation changed the preferential activation of genistein from ER?-LBD to ER?-LBD and further increased the slightly preferential activation of daidzein for ER?-LBD. The tested isoflavone compounds were less potent than E2 (around 5 to 1580 times for the aglycones) but modulated the LBD-coregulator interactions in a manner similar to E2. Our results show that genistein and daidzein remain agonistic ligands of ER?-LBD and ER?-LBD in their conjugated form with a higher relative preference for ER?-LBD than the corresponding aglycones. This shift in receptor preference is of special interest as the preferential activation of ER? is considered one of the possible modes of action underlying the supposed beneficial instead of adverse health effects of isoflavones. PMID:26361015

  15. An ab initio-based ErHe interatomic potential in hcp Er

    SciTech Connect

    Yang, Li; ye, Yeting; Fan, K. M.; Shen, Huahai; Peng, Shuming; Long, XG; Zhou, X. S.; Zu, Xiaotao; Gao, Fei

    2014-09-01

    We have developed an empirical erbium-helium (Er-He) potential by fitting to the results calculated from ab initio method. Based on the electronic hybridization between Er and He atoms, an s-band model, along with a repulsive pair potential, has been derived to describe the Er-He interaction. The atomic configurations and the formation energies of single He defects, small He interstitial clusters (Hen) and He-vacancy (HenV ) clusters obtained by ab initio calculations are used as the fitting database. The binding energies and relative stabilities of the HnVm clusters are studied by the present potential and compared with the ab initio calculations. The Er-He potential is also applied to study the migration of He in hcp-Er at different temperatures, and He clustering is found to occur at 600 K in hcp Er crystal, which may be due to the anisotropic migration behavior of He interstitials.

  16. An ab initio-based Er-He interatomic potential in hcp Er

    NASA Astrophysics Data System (ADS)

    Yang, L.; Ye, Y. T.; Fan, K. M.; Shen, H. H.; Peng, S. M.; Long, X. G.; Zhou, X. S.; Zu, X. T.; Gao, F.

    2014-09-01

    We have developed an empirical erbium-helium (Er-He) potential by fitting to the results calculated from the ab initio method. Based on the electronic hybridization between Er and He atoms, an s-band model, along with a repulsive pair potential, has been derived to describe the Er-He interaction. The atomic configurations and the formation energies of single He defects, small He interstitial clusters (Hen) and He-vacancy (HenV) clusters obtained by ab initio calculations are used as the fitting database. The binding energies and relative stabilities of the HnVm clusters are studied by the present potential and compared with the ab initio calculations. The Er-He potential is also applied to study the migration of He in hcp Er at different temperatures, and He clustering is found to occur at 600 K in hcp Er crystal, which may be due to the anisotropic migration behavior of He interstitials.

  17. FIRE_AX_ER2_MAS

    Atmospheric Science Data Center

    2015-11-24

    ... Stratocumulus Transition Experiment (ASTEX) ER-2 MODIS Airborne Simulator (MAS) Data Project Title:  MAS ... Temporal Resolution:  Each granule contains one flight track File Format:  HDF Tools:  ...

  18. FIRE_ACE_ER2_MAS

    Atmospheric Science Data Center

    2015-10-28

    ... NASA ER-2 Moderate Resolution Imaging Spectrometer (MODIS) Airborne Simulator (MAS) Data Project Title:  MAS ... Fortran include file IDL Code Flight Tracks Related Data:  MAS Additional ...

  19. Environmental release summary (ERS) database CY 1997

    SciTech Connect

    Gleckler, B.P.

    1998-07-01

    This report discusses the Environmental Release Summary (ERS) database. The current needs of the Effluent and Environmental database is continually modified to fulfill monitoring (EEM) program (managed by Waste Management Federal Services of Hanford, Incorporated, Air and Water Services Organization). Changes are made to accurately calculate current releases, to affect how past releases are calculated. This document serves as a snap-shot of the database and software for the CY-1997 data and releases. This document contains all of the relevant data for calculating radioactive-airborne and liquid effluent. The ERS database is the official repository for the CY-1997 ERS release reports and the settings used to generate those reports. As part of the Tri-Party Agreement, FDH is committed to provide a hard copy of the ERS database for Washington State Department of Ecology, upon request. This document also serves as that hard copy for the last complete calendar year.

  20. Molecular Design, Synthesis, and Evaluation of SNIPER(ER) That Induces Proteasomal Degradation of ER?.

    PubMed

    Okuhira, Keiichiro; Demizu, Yosuke; Hattori, Takayuki; Ohoka, Nobumichi; Shibata, Norihito; Kurihara, Masaaki; Naito, Mikihiko

    2016-01-01

    Manipulation of protein stability using small molecules has a great potential for both basic research and clinical therapy. Based on our protein knockdown technology, we recently developed a novel small molecule SNIPER(ER) that targets the estrogen receptor alpha (ER?) for degradation via the ubiquitin-proteasome system. This chapter describes the design and synthesis of SNIPER(ER) compounds, and methods for the evaluation of their activity in cellular system. PMID:26585163

  1. Topography over South America from ERS altimetry

    NASA Technical Reports Server (NTRS)

    Brenner, Anita; Frey, Herb; DiMarzio, John; Tsaoussi, Lucia

    1997-01-01

    The results of the surface topography mapping of South America during the ERS-1 geodetic mission are presented. The altimeter waveforms, the range measurement, and the internal and Doppler range corrections were obtained. The atmospheric corrections and solid tides were calculated. Comparisons between Shuttle laser altimetry and ERS-1 altimetry grid showed good agreement. Satellite radar altimetry data can be used to improve the topographic knowledge of regions for which only poor elevation data currently exist.

  2. The ER-2 meteorological measurement system

    NASA Technical Reports Server (NTRS)

    Chan, K. Roland

    1990-01-01

    The objectives of ER-2 Meteorological Measurement System (MMS) are: (1) to measure the meteorological parameters (pressure, temperature, and the three dimensional wind vector) accurately; (2) to provide high resolution data on atmospheric state variables and aircraft flight track to ER-2 investigators on a timely basis; and (3) to conduct collaborative research in atmospheric dynamics and chemistry. A summary of progress and results are presented.

  3. The Aspergillus nidulans peripheral ER: disorganization by ER stress and persistence during mitosis.

    PubMed

    Markina-Iarrairaegui, Ane; Pantazopoulou, Areti; Espeso, Eduardo A; Pealva, Miguel A

    2013-01-01

    The genetically amenable fungus Aspergillus nidulans is well suited for cell biology studies involving the secretory pathway and its relationship with hyphal tip growth by apical extension. We exploited live-cell epifluorescence microscopy of the ER labeled with the translocon component Sec63, endogenously tagged with GFP, to study the organization of 'secretory' ER domains. The Sec63 A. nidulans ER network includes brightly fluorescent peripheral strands and more faintly labeled nuclear envelopes. In hyphae, the most abundant peripheral ER structures correspond to plasma membrane-associated strands that are polarized, but do not invade the hyphal tip dome, at least in part because the subapical collar of endocytic actin patches constrict the cortical strands in this region. Thus the subapical endocytic ring might provide an attachment for ER strands, thereby ensuring that the growing tip remains 'loaded' with secretory ER. Acute disruption of secretory ER function by reductive stress-mediated induction of the unfolded protein response results in the reversible aggregation of ER strands, cessation of exocytosis and swelling of the hyphal tips. The secretory ER is insensitive to brefeldin A treatment and does not undergo changes during mitosis, in agreement with the reports that apical extension continues at normal rates during this period. PMID:23826221

  4. Getting the better of ER stress.

    PubMed

    Mollereau, Bertrand; Mani, Serge; Napoletano, Francesco

    2014-12-01

    Research over the past few years has highlighted the ability of the unfolded protein response (UPR) to minimize the deleterious effects of accumulated misfolded proteins under both physiological and pathological conditions. The endoplasmic reticulum (ER) adapts to endogenous and exogenous stressors by expanding its protein-folding capacity and by stimulating protective processes such as autophagy and antioxidant responses. Although it is clear that severe ER stress can elicit cell death, several recent studies have shown that low levels of ER stress may actually be beneficial to cells by eliciting an adaptive UPR that 'preconditions' the cell to a subsequent lethal insult; this process is called ER hormesis. The findings have important implications for the treatment of a wide variety of diseases associated with defective proteostasis, including neurodegenerative diseases, diabetes, and cancer. Here, we review the physiological and pathological functions of the ER, with a particular focus on the molecular mechanisms that lead to ER hormesis and cellular protection, and discuss the implications for disease treatment. PMID:25354560

  5. Association of promoter methylation of ER? and ER? with sporadic breast cancer--a study from North India.

    PubMed

    Chattopadhyay, Shilpi; Deo, S V S; Shukla, N K; Husain, Syed Akhtar

    2014-08-01

    Methylations in estrogen receptor (ER) ? and ER? are known to be involved in the pathogenesis of breast cancer. Here, we explore the role of promoter methylation of estrogen receptors, ER? and ER?, in sporadic breast cancer cases from a North Indian population. To this end, association between ER? and ER? methylation status along with different clinicopathological parameters and its correlation with protein expression was examined. Four hundred eighty paired breast cancer tissue samples and adjacent normal controls from 240 sporadic breast cancer patients were included, and their clinical and demographic profiles were recorded. ER? and ER? methylation was determined by methylation-specific polymerase (MSP) chain reaction. Our findings demonstrate that methylation of ER? and ER? occurs in high frequency and appears to be a mechanism of gene silencing in our population. Furthermore, on performing stratified analysis, we observed strong associations between ER?/ER? methylation and ER, PR, and HER2 status, tumor size, clinical stage, and triple negative tumors. Thus, our study not only highlights the role of ER?/ER? methylation in breast cancer but also suggests the ER?/ER? methylation pattern as a biomarker for assessing breast cancer risk. PMID:24833090

  6. A phosphotyrosine switch determines the antitumor activity of ER?.

    PubMed

    Yuan, Bin; Cheng, Long; Chiang, Huai-Chin; Xu, Xiaojie; Han, Yongjian; Su, Hang; Wang, Lingxue; Zhang, Bo; Lin, Jing; Li, Xiaobing; Xie, Xiangyang; Wang, Tao; Tekmal, Rajeshwar R; Curiel, Tyler J; Yuan, Zhi-Min; Elledge, Richard; Hu, Yanfen; Ye, Qinong; Li, Rong

    2014-08-01

    Estrogen receptors ER? and ER? share considerable sequence homology yet exert opposite effects on breast cancer cell proliferation. While the proliferative role of ER? in breast tumors is well characterized, it is not clear whether the antitumor activity of ER? can be mobilized in breast cancer cells. Here, we have shown that phosphorylation of a tyrosine residue (Y36) present in ER?, but not in ER?, dictates ER?-specific activation of transcription and is required for ER?-dependent inhibition of cancer cell growth in culture and in murine xenografts. Additionally, the c-ABL tyrosine kinase and EYA2 phosphatase directly and diametrically controlled the phosphorylation status of Y36 and subsequent ER? function. A nonphosphorylatable, transcriptionally active ER? mutant retained antitumor activity but circumvented control by upstream regulators. Phosphorylation of Y36 was required for ER?-mediated coactivator recruitment to ER? target promoters. In human breast cancer samples, elevated phosphorylation of Y36 in ER? correlated with high levels of c-ABL but low EYA2 levels. Furthermore, compared with total ER?, the presence of phosphorylated Y36-specific ER? was strongly associated with both disease-free and overall survival in patients with stage II and III disease. Together, these data identify a signaling circuitry that regulates ER?-specific antitumor activity and has potential as both a prognostic tool and a molecular target for cancer therapy. PMID:24960160

  7. Extended-release hydrocodone (Hysingla ER) for pain.

    PubMed

    2015-05-11

    Hysingla ER, the second single-ingredient extended-release hydrocodone product to become available in the US, is formulated for once-daily use. Zohydro ER is dosed twice daily and costs more. Both Hysingla ER and the new formulation of Zohydro ER have abuse-deterrent properties, but they will still be subject to misuse. PMID:25941956

  8. [The function of ER? in male reproductive system].

    PubMed

    Dong, Yu-Hang; Wei, Jin-Hua; Li, Zhen

    2014-12-01

    Estrogen receptors (ERs), including two sub-types ER? and ER?, belong to the steroid hormone superfamily of nuclear receptors. ER? distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ER? in the male reproductive system, and explored the mechanism of ER? in regulating the male reproductive system by analyzing different animal models of disrupted ER?. PMID:25872345

  9. Local compositional environment of Er in ZnS:ErF3 thin film electroluminescent phosphors

    NASA Astrophysics Data System (ADS)

    Davidson, Mark R.; Stoupin, Stanislav; DeVito, David; Collingwood, Joanna F.; Segre, Carlo; Holloway, Paul H.

    2011-03-01

    ZnS:Er thin film electroluminescent phosphors have been shown to exhibit a marked maximum in the near infrared emission (NIR) after a 425 C post-deposition anneal with a very narrow temperature window of 25 C for optimal NIR emission. Extended X-ray absorption fine structure (EXAFS) spectroscopy has been obtained from both the Zn and Er edges in order to examine the local structure of the host and dopant in this NIR phosphor material. Interestingly, the addition of only 0.5 mol. % of Er as ErF3 into the host is found to reduce the Zn-S bond length of one of the two nearest Zn-S shells by 0.6 relative to high-quality, atomic layer epitaxy (ALE) grown, pure ZnS. The coordination number of this shorter Zn-S bond increases after the optimal 425 C anneal. Longer range fits indicate a highly disordered structure, overall, consistent with earlier TEM results. Erbium-L3 EXAFS data from the second and third shells show increasing crystallinity with increasing annealing temperature in the vicinity of the Er dopant. Data from the first shell cannot be fit with S atoms, but are fit equally well with either O or F. Comparison with earlier analyses indicates that the Er is most likely surrounded by F in the first shell. Based on these data and previous studies, we develop a model in which the Er dopant is present as an Er:Fx complex with associated S vacancies, which may include one sulfur atom remaining in the Er nearest shell. Upon annealing, there is a reduction in the F present and a rearrangement of the crystal structure in the vicinity of the Er atom. Optimum annealing conditions occur when optimal crystalline environment is achieved prior to the loss of too much F from the Er:Fx complex.

  10. Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer

    PubMed Central

    Zhou, Wenbin; Xue, Jinqiu; Cheng, Lin; Lou, Peipei; Li, Chunlian; Wang, Ying; Wei, Ji-Fu; Ding, Qiang

    2015-01-01

    Estrogen receptors (ERs), including ER? and ER?, mainly mediate the genotype effect of estrogen. ER? is highly expressed in most breast cancers. Endocrine therapy is the most effective and safety adjunctive therapy for ER positive breast cancers. RNPC1, an RNA binding protein (RBP), post-transcriptionally regulating gene expression, is emerging as a critical mechanism for gene regulation in mammalian cells. In this study, we revealed RNPC1's capability of regulating ER? expression. There was a significant correlation between RNPC1 and ER? expression in breast cancer tissues. Ectopic expression of RNPC1 could increase ER? transcript and expression in breast cancer cells, and vice versa. Consistent with this, RNPC1 was able to bind to ER? transcript to increase its stability. Furthermore, overexpression of ER? could decrease the level of RNPC1 transcript and protein. It suggested a novel mechanism by which ER? expression was regulated via stabilizing mRNA. A regulatory feedback loop between RNPC1 and ER? was proved. It indicated that RNPC1 played a crucial role in ER? regulation in ER-positive breast cancers via binding to ER? mRNA. These findings might provide new insights into breast cancer endocrine therapy and ER? research. PMID:25881544

  11. The changing role of ER in endocrine resistance.

    PubMed

    Nardone, Agostina; De Angelis, Carmine; Trivedi, Meghana V; Osborne, C Kent; Schiff, Rachel

    2015-11-01

    Estrogen receptor (ER) is expressed in approximately 70% of newly diagnosed breast tumors. Although endocrine therapy targeting ER is highly effective, intrinsic or acquired resistance is common, significantly jeopardizing treatment outcomes and minimizing overall survival. Even in the presence of endocrine resistance, a continued role of ER signaling is suggested by several lines of clinical and preclinical evidence. Indeed, inhibition or down-regulation of ER reduces tumor growth in preclinical models of acquired endocrine resistance, and many patients with recurrent ER+ breast tumors progressing on one type of ER-targeted treatment still benefit from sequential endocrine treatments that target ER by a different mechanism. New insights into the nature and biology of ER have revealed several mechanisms sustaining altered ER signaling in endocrine-resistant tumors, including deregulated growth factor receptor signaling that results in ligand-independent ER activation, unbalanced ER co-regulator activity, and genomic alterations involving the ER gene ESR1. Therefore, biopsies of recurrent lesions are needed to assess the changes in epi/genomics and signaling landscape of ER and associated pathways in order to tailor therapies to effectively overcome endocrine resistance. In addition, more completely abolishing the levels and activity of ER and its co-activators, in combination with selected signal transduction inhibitors or agents blocking the upstream or downstream targets of the ER pathway, may provide a better therapeutic strategy in combating endocrine resistance. PMID:26271713

  12. a Dynamic Study of AN Electro-Rheological (er) Clutch

    NASA Astrophysics Data System (ADS)

    Tan, K. P.; Stanway, R.; Bullough, W. A.

    Electro-rheological (ER) fluid devices are smart actuators that possess several advantages such as controllable output dynamics and fast speed of response. Due to these output capabilities, an ER clutch is studied for the possibility of actuating the robotic arm. This is achieved by laying a few objectives. The main focus of this paper is to perform model validations of an ER velocity response of this ER clutch. Next, it is aimed to determine a method for rapid energization and de-energization of the ER output velocity for delivering fast start-stop robotic motions. The third aim is to employ the trend study on the ER output velocity response in order to define suitable input parameters for optimum ER robotic performances. The final aim is to determine the reliability of the tested ER fluids shearing in the ER clutch for long-term robotic applications.

  13. ARM CLASIC ER2 CRS/EDOP

    SciTech Connect

    Gerald Heymsfield

    2010-12-20

    Data was taken with the NASA ER-2 aircraft with the Cloud Radar System and other instruments in conjunction with the DOE ARM CLASIC field campaign. The flights were near the SGP site in north Central Oklahoma and targeted small developing convection. The CRS is a 94 GHz nadir pointing Doppler radar. Also on board the ER-2 was the Cloud Physics Lidar (CPL). Seven science flights were conducted but the weather conditions did not cooperate in that there was neither developing convection, or there was heavy rain.

  14. Low temperature properties of some Er-rich intermetallic compounds

    SciTech Connect

    K.A. Gshneidner,jr; A.O. Pecharsky; L.Hale; V.K. Pecharsky

    2004-09-30

    The low temperature volumetric heat capacity ({approx}3.5 to 350 K) and magnetic susceptibility ({approx}4 to 320 K) of Er{sub 3}Rh, Er{sub 3}Ir, Er{sub 3}Pt, Er{sub 2}Al, and Er{sub 2}Sn have been measured. All of the compounds order antiferromagnetically (or ferrimagnetically), and most exhibit more than one magnetic ordering transition. The volumetric heat capacities in general are smaller than those of the prototype magnetic regenerator materials, except for Er{sub 3}Ir in the 12 to 14 K temperature range.

  15. Opana() ER induced thrombotic thrombocytopenic purpura.

    PubMed

    Kotbi, Nabil; Han, Bernadine; Cheng, Duncan; Odom, Anna E

    2015-01-01

    We present the case of a patient who developed thrombotic thrombocytopenic purpura (TTP) following intravenous injection of Opana() ER. TTP reemerged after three months of abstinence with Opana misuse. This case report brings awareness to the possibility of developing TTP in those who misuse Opana, which is a growing concern. PMID:25995651

  16. Opana ER induced thrombotic thrombocytopenic purpura

    PubMed Central

    Kotbi, Nabil; Han, Bernadine; Cheng, Duncan; Odom, Anna E

    2015-01-01

    We present the case of a patient who developed thrombotic thrombocytopenic purpura (TTP) following intravenous injection of Opana ER. TTP reemerged after three months of abstinence with Opana misuse. This case report brings awareness to the possibility of developing TTP in those who misuse Opana, which is a growing concern. PMID:25995651

  17. European Space Agency, ERS-1 program

    NASA Technical Reports Server (NTRS)

    Haskell, A.

    1983-01-01

    The objectives selected for ERS-1 which are primarily intended to facilitate the exploitation of coastal oceans, including ice infested waters, and to facilitate the development of improved global weather information through the provision of information on the weather conditions over the oceans of the word are outlined. Additionally, land objectives will be addressed using the synthetic aperture radar incorporated in the payload.

  18. ER - the key to the highway.

    PubMed

    Stefano, Giovanni; Hawes, Chris; Brandizzi, Federica

    2014-12-01

    The endoplasmic reticulum (ER) is the key organelle at the start of the secretory pathway and the list of its functions is continually growing. The ER organization as a tubular/cisternal network at the cortex of plant cells has recently been shown to be governed by the membrane tubulation proteins of the reticulon family working alongside plant atlastin homologues, members of the RHD3 group of proteins. Such a network has intimate connections with other organelles such as peroxisomes via peroxules, chloroplasts, Golgi bodies and at the cell cortex to the plasma membrane with cytoskeleton at so called 'anchor/contact sites'. The ER network is by no means static displaying a range of different movements and acting as a subcellular highway supports the motility of organelles such as peroxisomes, mitochondria and Golgi bodies plus the transport of macromolecules such as viral movement proteins, nucleocapsid proteins and RNA. Here we highlight recent and exciting discoveries on the maintenance of the ER structure and its role on movement and biology of other organelles. PMID:25259957

  19. Creating Smart-er Cities: An Overview

    ERIC Educational Resources Information Center

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often…

  20. The QuEChERS revolution

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The technique of QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) is only 7 years old, yet it is revolutionizing the manner in which multiresidue, multiclass pesticide analysis (and perhaps beyond) is performed. Columnist Ron Majors sits down with inventors Steve Lehotay and Michelangelo An...

  1. Creating Smart-er Cities: An Overview

    ERIC Educational Resources Information Center

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often

  2. PingER History and Methodology

    SciTech Connect

    Cottrell, L

    2003-10-01

    This paper describes the methodology of the PingER toolkit/project. It provides some examples of how the results have been used to identify evolutionary changes in WAN response times and connectivity quality over the past 10 years, as well as some of the challenges faced in maintaining and deploying the system.

  3. ER the key to the highway

    PubMed Central

    Stefano, Giovanni; Hawes, Chris; Brandizzi, Federica

    2014-01-01

    The endoplasmic reticulum (ER) is the key organelle at the start of the secretory pathway and the list of its functions is continually growing. The ER organization as a tubular/cisternal network at the cortex of plant cells has recently been shown to be governed by the membrane tubulation proteins of the reticulon family working alongside plant atlastin homologues, members of the RHD3 group of proteins. Such a network has intimate connections with other organelles such as peroxisomes via peroxules, chloroplasts, Golgi bodies and at the cell cortex to the plasma membrane with cytoskeleton at so called anchor/contact sites. The ER network is by no means static displaying a range of different movements and acting as a sub-cellular highway supports the motility of organelles such as peroxisomes, mitochondria and Golgi bodies plus the transport of macromolecules such as viral movement proteins, nucleocapsid proteins and RNA. Here we highlight recent and exciting discoveries on the maintenance of the ER structure and its role on movement and biology of other organelles. PMID:25259957

  4. 155. Credit ER. Hand cleaning and trimming of Coleman canal ...

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

    155. Credit ER. Hand cleaning and trimming of Coleman canal after excavation by steam shovel. (ER, v. 64 1911 p. 701). - Battle Creek Hydroelectric System, Battle Creek & Tributaries, Red Bluff, Tehama County, CA

  5. 150. Credit ER. Building reinforced concrete portion of Coleman Canal ...

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

    150. Credit ER. Building reinforced concrete portion of Coleman Canal inverted siphon #2. Longitudinal steel reinforcing rods are visible at bottom. (ER, v. 64 1911 p. 702). - Battle Creek Hydroelectric System, Battle Creek & Tributaries, Red Bluff, Tehama County, CA

  6. ERs Often 'Safety Net' Care for People with Schizophrenia: CDC

    MedlinePLUS

    ... ERs Often 'Safety Net' Care for People With Schizophrenia: CDC Report finds more than 380,000 ER ... that, too often, under-medicated Americans suffering from schizophrenia end up seeking care in the nation's hospital ...

  7. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress.

    PubMed

    Verfaillie, T; Rubio, N; Garg, A D; Bultynck, G; Rizzuto, R; Decuypere, J-P; Piette, J; Linehan, C; Gupta, S; Samali, A; Agostinis, P

    2012-11-01

    Endoplasmic reticulum stress is emerging as an important modulator of different pathologies and as a mechanism contributing to cancer cell death in response to therapeutic agents. In several instances, oxidative stress and the onset of endoplasmic reticulum (ER) stress occur together; yet, the molecular events linking reactive oxygen species (ROS) to ER stress-mediated apoptosis are currently unknown. Here, we show that PERK (RNA-dependent protein kinase (PKR)-like ER kinase), a key ER stress sensor of the unfolded protein response, is uniquely enriched at the mitochondria-associated ER membranes (MAMs). PERK(-/-) cells display disturbed ER morphology and Ca(2+) signaling as well as significantly weaker ER-mitochondria contact sites. Re-expression of a kinase-dead PERK mutant but not the cytoplasmic deletion mutant of PERK in PERK(-/-) cells re-establishes ER-mitochondria juxtapositions and mitochondrial sensitization to ROS-mediated stress. In contrast to the canonical ER stressor thapsigargin, during ROS-mediated ER stress, PERK contributes to apoptosis twofold by sustaining the levels of pro-apoptotic C/EBP homologous protein (CHOP) and by facilitating the propagation of ROS signals between the ER and mitochondria through its tethering function. Hence, this study reveals an unprecedented role of PERK as a MAMs component required to maintain the ER-mitochondria juxtapositions and propel ROS-mediated mitochondrial apoptosis. Furthermore, it suggests that loss of PERK may cause defects in cell death sensitivity in pathological conditions linked to ROS-mediated ER stress. PMID:22705852

  8. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress

    PubMed Central

    Verfaillie, T; Rubio, N; Garg, A D; Bultynck, G; Rizzuto, R; Decuypere, J-P; Piette, J; Linehan, C; Gupta, S; Samali, A; Agostinis, P

    2012-01-01

    Endoplasmic reticulum stress is emerging as an important modulator of different pathologies and as a mechanism contributing to cancer cell death in response to therapeutic agents. In several instances, oxidative stress and the onset of endoplasmic reticulum (ER) stress occur together; yet, the molecular events linking reactive oxygen species (ROS) to ER stress-mediated apoptosis are currently unknown. Here, we show that PERK (RNA-dependent protein kinase (PKR)-like ER kinase), a key ER stress sensor of the unfolded protein response, is uniquely enriched at the mitochondria-associated ER membranes (MAMs). PERK?/? cells display disturbed ER morphology and Ca2+ signaling as well as significantly weaker ER-mitochondria contact sites. Re-expression of a kinase-dead PERK mutant but not the cytoplasmic deletion mutant of PERK in PERK?/? cells re-establishes ER-mitochondria juxtapositions and mitochondrial sensitization to ROS-mediated stress. In contrast to the canonical ER stressor thapsigargin, during ROS-mediated ER stress, PERK contributes to apoptosis twofold by sustaining the levels of pro-apoptotic C/EBP homologous protein (CHOP) and by facilitating the propagation of ROS signals between the ER and mitochondria through its tethering function. Hence, this study reveals an unprecedented role of PERK as a MAMs component required to maintain the ER-mitochondria juxtapositions and propel ROS-mediated mitochondrial apoptosis. Furthermore, it suggests that loss of PERK may cause defects in cell death sensitivity in pathological conditions linked to ROS-mediated ER stress. PMID:22705852

  9. Different Proliferation Patterns in Breast Cancer: AgNOR Measurements in ER-Negative and ER-Positive Tumor Cells

    PubMed Central

    Gnther, Lukas; Hufnagl, Peter; Winzer, Klaus?Jrgen; Guski, Hans

    2000-01-01

    The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs) in situ within human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER?positive and ER?negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER?positive and ER?negative cells and other prognostic factors of breast cancer [BloomRichardson?Grading and growth fraction (Ki?67 index)] were investigated. A higher AgNOR content in ER?negative cells and a special clustering phenomenon in ER?positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER?negative cells. ER?negative cells of breast cancer can be characterized as the more malignant and possibly prognosis?dictating cell fraction. Thus, ER?negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER?positive cells. We recommend measurement AgNORs exclusively in ER?negative cells of breast cancer. PMID:11205318

  10. ER-associated retrograde SNAREs and the Dsl1 complex mediate an alternative, Sey1p-independent homotypic ER fusion pathway

    PubMed Central

    Rogers, Jason V.; McMahon, Conor; Baryshnikova, Anastasia; Hughson, Frederick M.; Rose, Mark D.

    2014-01-01

    The peripheral endoplasmic reticulum (ER) network is dynamically maintained by homotypic (ERER) fusion. In Saccharomyces cerevisiae, the dynamin-like GTPase Sey1p can mediate ERER fusion, but sey1? cells have no growth defect and only slightly perturbed ER structure. Recent work suggested that ER-localized soluble N-ethylmaleimidesensitive factor attachment protein receptors (SNAREs) mediate a Sey1p-independent ERER fusion pathway. However, an alternative explanationthat the observed phenotypes arose from perturbed vesicle traffickingcould not be ruled out. In this study, we used candidate and synthetic genetic array (SGA) approaches to more fully characterize SNARE-mediated ERER fusion. We found that Dsl1 complex mutations in sey1? cells cause strong synthetic growth and ER structure defects and delayed ERER fusion in vivo, additionally implicating the Dsl1 complex in SNARE-mediated ERER fusion. In contrast, cytosolic coat protein I (COPI) vesicle coat mutations in sey1? cells caused no synthetic defects, excluding perturbed retrograde trafficking as a cause for the previously observed synthetic defects. Finally, deleting the reticulons that help maintain ER architecture in cells disrupted for both ERER fusion pathways caused almost complete inviability. We conclude that the ER SNAREs and the Dsl1 complex directly mediate Sey1p-independent ERER fusion and that, in the absence of both pathways, cell viability depends upon membrane curvaturepromoting reticulons. PMID:25187651

  11. Rotational band properties in {sup 165}Er

    SciTech Connect

    Wang, S. T.; Zhou, X. H.; Zhang, Y. H.; Zheng, Y.; Liu, M. L.; Chen, L.; Zhang, N. T.; Hua, W.; Guo, S.; Qiang, Y. H.; Li, G. S.; Ding, B.; Shi, Y.; Xu, F. R.

    2011-07-15

    High-spin states in {sup 165}Er have been studied experimentally using the {sup 160}Gd({sup 9}Be, 4n) reaction at beam energies of 42 and 45 MeV. The previously known bands based on the 5/2{sup +}[642], 5/2{sup -}[523], and 11/2{sup -}[505] configurations are extended to (49/2{sup +}), (45/2{sup -}), and (31/2{sup -}) states, respectively. The rotational bands in {sup 165}Er generally show gradual alignment processes, indicating strong band interactions associated with the i{sub 13/2} neutron alignments. The band properties are compared with those in the neighboring nuclei and discussed within the framework of the cranked shell model.

  12. Optical properties of Er(3+)-doped oxyfluoride glasses.

    PubMed

    Feng, Li; Wu, Yinsu

    2016-02-15

    Er(3+)-singly doped and Er(3+)/Yb(3+)-codoped 50SiO2-(50-x)BaF2-xZnF2(SBZx) oxyfluoride glasses are prepared and the optical properties of Er(3+)-singly doped glasses are investigated by using the Judd-Ofelt theory. Bright green and red upconversion luminescence of Er(3+)/Yb(3+)-codoped glasses is obtained under 980nm excitation. Furthermore, factors affecting this phenomenon such as glass composition, doping concentration of Er(3+) and Yb(3+) ions, and pump power are discussed in details. PMID:26613336

  13. Optical properties of Er3 +-doped oxyfluoride glasses

    NASA Astrophysics Data System (ADS)

    Feng, Li; Wu, Yinsu

    2016-02-01

    Er3 +-singly doped and Er3 +/Yb3 +-codoped 50SiO2-(50 - x)BaF2-xZnF2(SBZx) oxyfluoride glasses are prepared and the optical properties of Er3 +-singly doped glasses are investigated by using the Judd-Ofelt theory. Bright green and red upconversion luminescence of Er3 +/Yb3 +-codoped glasses is obtained under 980 nm excitation. Furthermore, factors affecting this phenomenon such as glass composition, doping concentration of Er3 + and Yb3 + ions, and pump power are discussed in details.

  14. MicroRNAs meet calcium: joint venture in ER proteostasis.

    PubMed

    Finger, Fabian; Hoppe, Thorsten

    2014-11-01

    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. PMID:25372053

  15. Calibration: Practical experience with ERS-1

    NASA Technical Reports Server (NTRS)

    Louet, Jacques

    1993-01-01

    Viewgraphs and discussion of calibration:practical experience with ERS-1 are presented. Topics covered include: radiometric calibration, geometric calibration, phase calibration, and polarimetric calibration. Basic synthetic aperture radar (SAR) measurement parameters are radar backscattering, target position, target speed, and polarization. SAR calibration facilitates quantitative measurements needed to derive geophysical parameters of the area under observation from basic SAR measurements (e.g. soil moisture, biomass, ocean wave energy, ocean currents, ice type, and ice flow).

  16. ER-12-1 completion report

    SciTech Connect

    Russell, C.E.; Gillespie, D.; Cole, J.C.; Drellack, S.L.

    1996-12-01

    The objective of drillhole ER-12-1 was to determine the hydrogeology of paleozoic carbonate rocks and of the Eleana Formation, a regional aquitard, in an area potentially downgradient from underground nuclear testing conducted in nearby Rainier Mesa. This objective was addressed through the drilling of well ER-12-1 at N886,640.26 E640,538.85 Nevada Central Coordinates. Drilling of the 1094 m (3588 ft) well began on July 19, 1991 and was completed on October 17, 1991. Drilling problems included hole deviation and hole instability that prevented the timely completion of this borehole. Drilling methods used include rotary tri-cone and rotary hammer drilling with conventional and reverse circulation using air/water, air/foam (Davis mix), and bentonite mud. Geologic cuttings and geophysical logs were obtained from the well. The rocks penetrated by the ER-12-1 drillhole are a complex assemblage of Silurian, Devonian, and Mississippian sedimentary rocks that are bounded by numerous faults that show substantial stratigraphic offset. The final 7.3 m (24 ft) of this hole penetrated an unusual intrusive rock of Cretaceous age. The geology of this borehole was substantially different from that expected, with the Tongue Wash Fault encountered at a much shallower depth, paleozoic rocks shuffled out of stratigraphic sequence, and the presence of an altered biotite-rich microporphyritic igneous rock at the bottom of the borehole. Conodont CAI analyses and rock pyrolysis analyses indicate that the carbonate rocks in ER-12-1, as well as the intervening sheets of Eleana siltstone, have been thermally overprinted following movement on the faults that separate them. The probable source of heat for this thermal disturbance is the microporphyritic intrusion encountered at the bottom of the hole, and its age establishes that the major fault activity must have occurred prior to 102.3+0.5 Ma (middle Cretaceous).

  17. ER contact sites direct late endosome transport.

    PubMed

    Wijdeven, Ruud H; Jongsma, Marlieke L M; Neefjes, Jacques; Berlin, Ilana

    2015-12-01

    Endosomes shuttle select cargoes between cellular compartments and, in doing so, maintain intracellular homeostasis and enable interactions with the extracellular space. Directionality of endosomal transport critically impinges on cargo fate, as retrograde (microtubule minus-end directed) traffic delivers vesicle contents to the lysosome for proteolysis, while the opposing anterograde (plus-end directed) movement promotes recycling and secretion. Intriguingly, the endoplasmic reticulum (ER) is emerging as a key player in spatiotemporal control of late endosome and lysosome transport, through the establishment of physical contacts with these organelles. Earlier studies have described how minus-end-directed motor proteins become discharged from vesicles engaged at such contact sites. Now, Raiborg et al. implicate ER-mediated interactions, induced by protrudin, in loading plus-end-directed motor kinesin-1 onto endosomes, thereby stimulating their transport toward the cell's periphery. In this review, we recast the prevailing concepts on bidirectional late endosome transport and discuss the emerging paradigm of inter-compartmental regulation from the ER-endosome interface viewpoint. PMID:26440125

  18. The Performance of the ERS-2 SAR after 15 Years

    NASA Astrophysics Data System (ADS)

    Meadows, Peter; Miranda, Nuno; Pilgrim, Alan; Griffiths, Emma

    2010-12-01

    The European Space Agency (ESA) ERS-2 Synthetic Aperture Radar (SAR) has successfully operated for more than 15 years (since April 1995). The performance of the ERS-SAR is routinely assessed via a variety of quality assessment and calibration measures. This paper gives the latest ERS-2 SAR quality assessment and calibration results, including elevation antenna pattern estimation and monitoring, updates to ERS-2 SAR internal calibration and stability, noise equivalent radar cross-section measurements, updates to the ERS-2 nominal replica pulse correction table and image localisation results. Equations are given for the calculation of distributed and point target radar cross-sections from the multi- look ground range detected ERS-2.SAR.PRI/IMP and the single-look slant range complex ERS- 2.SAR.SLC/IMS products. Also given are ERS-2 attitude and SAR Doppler variations following the change from three to one gyroscope operations in February 2000 and the change to gyro-less operations in February 2001. A brief description is given of the evolution and harmonisation during 2006 of ERS SAR products from VMP to PGS-ERS processors and to the same specification as Envisat ASAR product. Finally, a problem from 2008 with the sampling window start times of some ERS-2 SAR acquisitions is described.

  19. Ultraviolet photoelectron spectra of Er2@C82 (I), Er2@C82 (III), Er2C2@C82 (I) and Er2C2@C82 (III)

    NASA Astrophysics Data System (ADS)

    Miyazaki, Takafumi; Sumii, Ryohei; Umemoto, Hisashi; Okimoto, Haruya; Ito, Yasuhiro; Sugai, Toshiki; Shinohara, Hisanori; Zaima, Takeyuki; Yagi, Hajime; Hino, Shojun

    2012-03-01

    Ultraviolet photoelectron spectra (UPS) and X-ray photoelectron spectra (XPS) of two erbium atoms and an erbium-carbide cluster entrapped fullerenes, Er2@C82 (I), Er2@C82 (III), Er2C2@C82 (I) and Er2C2@C82 (III), were measured using a synchrotron radiation light source and MgK? X-ray gun. The spectral onset energy of these endohedral fullerenes is around 0.8-0.9 eV, which is larger than that of Er@C82 (I) of 0.4 eV. The UPS of erbium atoms encapsulated endohedral fullerenes having the same C82 cage structure were analogous while those of the different cage structure are different. This finding supports an empirical rule that the electronic structure of the endohedral fullerenes is principally governed by the C82 cage structure. The XPS Er4d5/2 peak of Er2@C82 suggests the oxidation state of (Er)2 @C826-. The difference spectrum between the UPS of Er2@C82 (III) and Er2C2@C82 (III) has the same C3v structure reveals two excess electrons on the cage of Er2@C82.

  20. Aggressive Prostate Cancer Is Prevented in ER?KO Mice and Stimulated in ER?KO TRAMP Mice

    PubMed Central

    ?lusarz, Anna; Jackson, Glenn A.; Day, J. Kevin; Shenouda, Nader S.; Bogener, Jennifer L.; Browning, Jim D.; Fritsche, Kevin L.; MacDonald, Ruth S.; Besch-Williford, Cynthia L.

    2012-01-01

    Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ER? or ER? to play a protective role against prostate cancer, we bred transgenic mice lacking functional ER? or ER? with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ER? knockout (KO) or ER?KO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ER?KO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ER?KO mice to 41%. Interestingly, immunohistochemical analysis showed ER? expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ER? location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ER? vs. ER? would result in prevention of advanced prostate cancer. PMID:22753646

  1. Tamoxifen Action in ER-Negative Breast Cancer

    PubMed Central

    Manna, Subrata; Holz, Marina K.

    2016-01-01

    Breast cancer is a highly heterogeneous disease. Tamoxifen is a selective estrogen receptor (ER) modulator and is mainly indicated for the treatment of breast cancer in postmenopausal women and postsurgery neoadjuvant therapy in ER-positive breast cancers. Interestingly, 5–10% of the ER-negative breast cancers have also shown sensitivity to tamoxifen treatment. The involvement of molecular markers and/or signaling pathways independent of ER signaling has been implicated in tamoxifen sensitivity in the ER-negative subgroup. Studies reveal that variation in the expression of estrogen-related receptor alpha, ER subtype beta, tumor microenvironment, and epigenetics affects tamoxifen sensitivity. This review discusses the background of the research on the action of tamoxifen that may inspire future studies to explore effective therapeutic strategies for the treatment of ER-negative and triple-negative breast cancers, the latter being an aggressive disease with worse clinical outcome. PMID:26989346

  2. Practice-Relevant Aspects of Constructing ER Fluid Actuators

    NASA Astrophysics Data System (ADS)

    Janocha, H.; Rech, B.; Bölter, R.

    The flow resistance of electrorheological fluids (ER fluids) can be controlled by applying electric fields. Thus, ER fluids are suitable for the application in actuators, using high-voltage sources for the generation of the field. The behaviour of an ER fluid actuator not only depends on the properties of the individual actuator components (ER fluid, energy transducer and energy source) but especially on their combined efforts as a system. Based on a possible scheme for the design of ER fluid actuators, this paper presents important practice-relevant aspects of a systematic actuator construction. Here the behaviour of a commercial ER suspension is examined and compared to a homogeneous ER fluid without yield point using a rotational viscometer and a flow-mode damper realized at the Laboratory of Process Automation (LPA) of the University of Saarland.

  3. The ER quality control and ER associated degradation machineries are vital for viral pathogenesis

    PubMed Central

    Verchot, Jeanmarie

    2014-01-01

    The endoplasmic reticulum (ER) is central to protein production and membrane lipid synthesis. The unfolded protein response (UPR) supports cellular metabolism by ensuring protein quality control in the ER. Most positive strand RNA viruses cause extensive remodeling of membranes and require active membrane synthesis to promote infection. How viruses interact with the cellular machinery controlling membrane metabolism is largely unknown. Furthermore, there is mounting data pointing to the importance of the UPR and ER associated degradation (ERAD) machineries in viral pathogenesis in eukaryotes emerging topic. For many viruses, the UPR is an early event that is essential for persistent infection and benefits virus replication. In addition, many viruses are reported to commandeer ER resident chaperones to contribute to virus replication and intercellular movement. In particular, calreticulin, the ubiquitin machinery, and the 26S proteasome are most commonly identified components of the UPR and ERAD machinery that also regulate virus infection. In addition, researchers have noted a link between UPR and autophagy. It is well accepted that positive strand RNA viruses use autophagic membranes as scaffolds to support replication and assembly. However this topic has yet to be explored using plant viruses. The goal of research on this topic is to uncover how viruses interact with this ER-related machinery and to use this information for designing novel strategies to boost immune responses to virus infection. PMID:24653727

  4. ER and Golgi stresses increase ER-Golgi SNARE Syntaxin5: Implications for organelle stress and ?APP processing.

    PubMed

    Suga, Kei; Saito, Ayako; Mishima, Tatsuya; Akagawa, Kimio

    2015-09-14

    Unresolved endoplasmic reticulum (ER) stress causes neuronal death and has been implicated in neurodegenerative conditions such as Alzheimer's disease (AD). However, the mechanisms by which stress signals propagate from the ER through the Golgi apparatus and their effects on the transport and processing of AD-related proteins, such as ?-amyloid precursor protein (?APP), are unknown. We recently found that in the NG108-15 cell line, ER stress upregulates ER-Golgi-soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (ER-Golgi SNAREs) Syx5 and Bet1. In the present study, we examined the effects of apoptosis and ER stress inducers on the expression of ER-Golgi SNARE proteins and cell viability in a primary culture of rat hippocampal neurons. An apoptosis inducer significantly downregulated the expression of ER-Golgi SNARE Syx5. ER-stress inducers upregulated the expression of Syx5 isoforms and Bet1 proteins via de novo synthesis of their mRNA transcripts. Knockdown of Syx5 during apoptosis or ER stress induction enhanced vulnerability of neurons. Additionally, we examined the effects of Golgi stress on Syx5 expression and ?APP processing. Golgi stress also induced upregulation of ER-Golgi SNARE Syx5, and concomitantly, suppressed amyloid-? peptide secretion. These findings suggest that Syx5 is a potential stress responsive factor that participates in ?APP processing and the survival pathways of neuronal cells. PMID:26219982

  5. Effects of Endogenous Ovarian Estrogen Versus Exogenous Estrogen Replacement on Blood Flow and ER? and ER? Levels in the Bladder

    PubMed Central

    Ablove, Tova S.; Austin, Jason L.; Phernetton, Terry M.; Magness, Ronald R.

    2011-01-01

    Objective Determine the effect of endogenous estrogen versus estrogen replacement therapy (ERT) on bladder blood flow (BBF) and estrogen receptors (ERs). Methods BBF was determined with radio-labeled microspheres in luteal, follicular, pregnant, oophorectomized (Ovx) sheep, and Ovx sheep with ERT. Estrogen receptors (ER?, ER?) were quantified using Western blot analysis. Results Compared to luteal and follicular ewes, BBF was reduced in pregnancy and following oophorectomy. Estrogen replacement therapy in Ovx sheep restored BBF to luteal levels. Estrogen receptor ? predominated, whereas ER? was not detectable. Estrogen receptor-? levels were unaffected by the ovarian cycle and increased in pregnancy, as well as in Ovx sheep with and without chronic ERT. Conclusion The combination of diminished BBF and elevated ER? levels in both pregnant and Ovx sheep suggests an inverse relationship between BBF and ER? in the bladder. Although chronic ERT in Ovx sheep restored BBF, it did not restore ER? back to luteal levels. PMID:19535742

  6. ER-?36-mediated rapid estrogen signaling positively regulates ER-positive breast cancer stem/progenitor cells.

    PubMed

    Deng, Hao; Zhang, Xin-Tian; Wang, Mo-Lin; Zheng, Hong-Yan; Liu, Li-Jiang; Wang, Zhao-Yi

    2014-01-01

    The breast cancer stem cells (BCSC) play important roles in breast cancer occurrence, recurrence and metastasis. However, the role of estrogen signaling, a signaling pathway important in development and progression of breast cancer, in regulation of BCSC has not been well established. Previously, we identified and cloned a variant of estrogen receptor ?, ER-?36, with a molecular weight of 36 kDa. ER-?36 lacks both transactivation domains AF-1 and AF-2 of the 66 kDa full-length ER-? (ER-?66) and mediates rapid estrogen signaling to promote proliferation of breast cancer cells. In this study, we aim to investigate the function and the underlying mechanism of ER-?36-mediated rapid estrogen signaling in growth regulation of the ER-positive breast cancer stem/progenitor cells. ER-positive breast cancer cells MCF7 and T47D as well as the variants with different levels of ER-?36 expression were used. The effects of estrogen on BCSC's abilities of growth, self-renewal, differentiation and tumor-seeding were examined using tumorsphere formation, flow cytometry, indirect immunofluorence staining and in vivo xenograft assays. The underlying mechanisms were also studied with Western-blot analysis. We found that 17-?-estradiol (E2?) treatment increased the population of ER-positive breast cancer stem/progenitor cells while failed to do so in the cells with knocked-down levels of ER-?36 expression. Cells with forced expression of recombinant ER-?36, however, responded strongly to E2? treatment by increasing growth in vitro and tumor-seeding efficiency in vivo. The rapid estrogen signaling via the AKT/GSK3? pathway is involved in estrogen-stimulated growth of ER-positive breast cancer stem/progenitor cells. We concluded that ER-?36-mediated rapid estrogen signaling plays an important role in regulation and maintenance of ER-positive breast cancer stem/progenitor cells. PMID:24558373

  7. On the Use of an ER-213 Detonator to Establish a Baseline for the ER-486

    SciTech Connect

    Thomas, Keith A.; Liechty, Gary H.; Jaramillo, Dennis C.; Munger, Alan C.; McHugh, Douglas C.; Kennedy, James E.

    2014-08-19

    This report documents a series of tests using a TSD-115 fireset coupled with an ER-213, a gold exploding bridgewire (EBW) detonator. These tests were designed to fire this EBW with a smaller fireset to obtain current and voltage data as well as timing information at voltage levels below, above, and throughout the threshold firing region. This study could then create a database for comparison to our current ER-486 EBW development, which is designed to be a lower voltage (<500V) device.

  8. Progesterone receptor modulates ER? action in breast cancer.

    PubMed

    Mohammed, Hisham; Russell, I Alasdair; Stark, Rory; Rueda, Oscar M; Hickey, Theresa E; Tarulli, Gerard A; Serandour, Aurelien A; Serandour, Aurelien A A; Birrell, Stephen N; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V; Brown, Gordon D; D'Santos, Clive; Robinson, Jessica L L; Silva, Grace; Launchbury, Rosalind; Perou, Charles M; Stingl, John; Caldas, Carlos; Tilley, Wayne D; Carroll, Jason S

    2015-07-16

    Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-? (ER?) function and breast cancer prognosis. Here we show that PR is not merely an ER?-induced gene target, but is also an ER?-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ER? to direct ER? chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ER?(+) cell line xenografts and primary ER?(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ER? antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ER?(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ER? chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions. PMID:26153859

  9. Caffeine attenuated ER stress-induced leptin resistance in neurons.

    PubMed

    Hosoi, Toru; Toyoda, Keisuke; Nakatsu, Kanako; Ozawa, Koichiro

    2014-05-21

    Exposing the endoplasmic reticulum (ER) to stress causes the accumulation of unfolded proteins, and subsequently results in ER stress. ER stress may be involved in various disorders such as obesity, diabetes, and neurodegenerative diseases. Leptin is an important circulating hormone, that inhibits food intake and accelerates energy consumption, which suppresses body weight gain. Recent studies demonstrated that leptin resistance is one of the main factors involved in the development of obesity. We and other groups recently reported the role of ER stress in the development of leptin resistance. Therefore, identifying drugs that target ER stress may be a promising fundamental strategy for the treatment of obesity. In the present study, we investigated whether caffeine could affect ER stress and the subsequent development of leptin resistance. We showed that caffeine exhibited chaperone activity, which attenuated protein aggregation. Caffeine also inhibited the ER stress-induced activation of IRE1 and PERK, which suggested the attenuation of ER stress. Moreover, caffeine markedly improved ER stress-induced impairments in the leptin-induced phosphorylation of STAT3. Therefore, these results suggest caffeine may have pharmacological properties that ameliorate leptin resistance by reducing ER stress. PMID:24699176

  10. Virus-induced ER stress and the unfolded protein response

    PubMed Central

    Zhang, Lingrui; Wang, Aiming

    2012-01-01

    The accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in ER stress that triggers cytoprotective signaling pathways, termed the unfolded protein response (UPR), to restore and maintain homeostasis in the ER or to induce apoptosis if ER stress remains unmitigated. The UPR signaling network encompasses three core elements, i.e., PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein-1 (IRE1). Activation of these three branch pathways of the UPR leads to the translation arrest and degradation of misfolded proteins, the expression of ER molecular chaperones, and the expansion of the ER membrane to decrease the load of proteins and increase the protein-folding capacity in the ER. Recently, the essential roles of the UPR have been implicated in a number of mammalian diseases, particularly viral diseases. In virus-infected cells, the cellular translation machinery is hijacked by the infecting virus to produce large amounts of viral proteins, which inevitably perturbs ER homeostasis and causes ER stress. This review summarizes current knowledge about the UPR signaling pathways, highlights two identified UPR pathways in plants, and discuss progress in elucidating the UPR in virus-infected cells and its functional roles in viral infection. PMID:23293645

  11. Apigenin Suppresses Cancer Cell Growth through ER?1

    PubMed Central

    Mak, Paul; Leung, Yuet-Kin; Tang, Wan-Yee; Harwood, Charlotte; Ho, Shuk-Mei

    2006-01-01

    Abstract Two flavonoids, genistein and apigenin, have been implicated as chemopreventive agents against prostate and breast cancers. However, the mechanisms behind their respective cancer-protective effects may vary significantly. The goal of this study was to determine whether the antiproliferative action of these flavonoids on prostate (DU-145) and breast (MDA-MB-231) cancer cells expressing only estrogen receptor (ER) ? is mediated by this ER subtype. It was found that both genistein and apigenin, although not 17?-estradiol, exhibited antiproliferative effects and proapoptotic activities through caspase-3 activation in these two cell lines. In yeast transcription assays, both flavonoids displayed high specificity toward ER? transactivation, particularly at lower concentrations. However, in mammalian assay, apigenin was found to be more ER?-selective than genistein, which has equal potency in inducing transactivation through ER? and ER?. Small interfering RNA-mediated downregulation of ER? abrogated the antiproliferative effect of apigenin in both cancer cells but did not reverse that of genistein. Our data unveil, for the first time, that the anticancer action of apigenin is mediated, in part, by ER?. The differential use of ER? and ER? signaling for transaction between genistein and apigenin demonstrates the complexity of phytoestrogen action in the context of their anticancer properties. PMID:17132221

  12. BOREAS Level-0 ER-2 Navigation Data

    NASA Technical Reports Server (NTRS)

    Strub, Richard; Dominguez, Roseanne; Newcomer, Jeffrey A.; Hall, Forrest G. (Editor)

    2000-01-01

    The BOREAS Staff Science effort covered those activities that were BOREAS community-level activities or required uniform data collection procedures across sites and time. These activities included the acquisition, processing, and archiving of aircraft navigation/attitude data to complement the digital image data. The level-0 ER-2 navigation data files contain aircraft attitude and position information acquired during the digital image and photographic data collection missions. Temporally, the data were acquired from April to September 1994. Data were recorded at intervals of 5 seconds. The data are stored in tabular ASCII files.

  13. ERS-1: 18 months in orbit

    NASA Technical Reports Server (NTRS)

    Louet, Jacques

    1993-01-01

    Viewgraphs of the ERS-1 mission outline initial objectives, the orbit configuration, the instrumentation, the international cooperation, and the objectives still to be achieved. Graphs of specified performances include orbit control, inclination correction, solar array power, satellite stability, AMI performance verification, SAR radiometric stability, and RA performance stability. Also displayed are the number of planned (for November 92 through February of 93) and acquired SAR frames of the mission for each of the various sites throughout Europe and the world. A map locating these chosen sites is also included.

  14. Obesity and endoplasmic reticulum (ER) stresses

    PubMed Central

    Tripathi, Yamini B.; Pandey, Vivek

    2012-01-01

    In obesity, the adipose cells behave as inflammatory source and result to low grade inflammation. This systemic inflammation along with oxidative stress is a silent killer and damages other vital organs also. High metabolic process, induced due to high nutritional intake, results to endoplasmic reticulum (ER) stress and mitochondrial stress. This review describes the triggering factor and basic mechanism behind the obesity mediated these stresses in relation to inflammation. Efforts have been made to describe the effect-response cycle between adipocytes and non-adipocyte cells with reference to metabolic syndrome (MS). PMID:22891067

  15. Expression of glucose transporter GLUT-1 and estrogen receptors ER-alpha and ER-beta in human breast cancer.

    PubMed

    Lauda?ski, P; Koda, M; Koz?owski, L; Swiatecka, J; Wojtukiewicz, M; Sulkowski, S; Wo?czy?ski, S

    2004-01-01

    We attempted to describe a GLUT-1 expression in breast cancer and characterize correlation between GLUT-1 and ERs alpha and beta expression as well as correlate this with clinicopathologic features. Sixty-nine patients were involved in the study. GLUT-1, ER-alpha and ER-beta immunocytochemistry was performed using the streptavidin- biotin method. Thirty-seven (53.6%) out of total 69 were GLUT-1 positive. Of GLUT- 1 positive 45.3% were ER-alpha-positive, whereas 81.3% of ER-alpha-negative were GLUT-1 positive. Statistically significant correlation was observed between GLUT-1 and ER-alpha expression status but neither between GLUT-1 and ER-beta nor with clinicopathologic features. No statistically significant correlation was found between expression level (expressed as immunocytoreactive score) of GLUT-1, ER-alpha and ER-beta. Since most of ER-alpha-negative (81.3%) were GLUT-1 positive and significant correlation exists between the two receptors it is reasonable to assume that some functional relation might exists between the expression of two receptors. PMID:15254667

  16. Dysfunction of Wntless triggers the retrograde Golgi-to-ER transport of Wingless and induces ER stress.

    PubMed

    Zhang, Peng; Zhou, Lujun; Pei, Chunli; Lin, Xinhua; Yuan, Zengqiang

    2016-01-01

    Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of-function or porcupine (porc) depletion, and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi-to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg, and elucidates a correlation between Wnt secretion and ER stress during development. PMID:26887613

  17. Expression of ER?, ER? and Her-2 and distribution of molecular subtypes in Uygur and Han patients with breast cancer.

    PubMed

    Guo, Liying; Hou, Xueqin; Dilimina, Yilamu; Wang, Bowei

    2014-05-01

    The aim of the present study was to investigate the expression levels of estrogen receptor (ER) ? and ? and human epidermal growth factor receptor-2 (Her-2), as well as the distribution of breast cancer molecular subtypes in Uygur and Han breast cancer patients. Cancer tissues were collected and analyzed from 709 breast cancer patients enrolled between January 2000 and December 2010. The expression levels of ER?, ER? and Her-2 were determined by immunohistochemistry. The differences in expression and molecular subtype distribution between Uygur and Han patients with breast cancer were analyzed using a Pearson's ?(2) test. Statistically significant differences were observed in the expression levels of ER?, ER? and Her-2 between the Uygur and Han patients with breast cancer (P<0.05). The expression levels of ER? (++), ER? (+++) and Her-2 (+++) in Uygur patients were significantly higher, while the expression levels of ER? (+++) in Uygur patients were significantly lower when compared with Han patients. The percentage of luminal A type breast cancer in Uygur patients was significantly lower when compared with the Han patients, whereas the percentages of basal-like and Her-2 overexpression types were significantly higher than those in Han patients (P<0.05). Therefore, expression levels of ER?, ER? and Her-2, and molecular subtypes of breast cancer were significantly different between the Uygur and Han populations. PMID:24940390

  18. Dysfunction of Wntless triggers the retrograde Golgi-to-ER transport of Wingless and induces ER stress

    PubMed Central

    Zhang, Peng; Zhou, Lujun; Pei, Chunli; Lin, Xinhua; Yuan, Zengqiang

    2016-01-01

    Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of-function or porcupine (porc) depletion, and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi-to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg, and elucidates a correlation between Wnt secretion and ER stress during development. PMID:26887613

  19. ER stress inhibits neuronal death by promoting autophagy.

    PubMed

    Fouillet, Antoine; Levet, Clemence; Virgone, Angelique; Robin, Marion; Dourlen, Pierre; Rieusset, Jennifer; Belaidi, Elise; Ovize, Michel; Touret, Monique; Nataf, Serge; Mollereau, Bertrand

    2012-06-01

    Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases but its relationship and role in disease progression remain unclear. Using genetic and pharmacological approaches, we showed that mild ER stress ("preconditioning") is neuroprotective in Drosophila and mouse models of Parkinson disease. In addition, we found that the combination of mild ER stress and apoptotic signals triggers an autophagic response both in vivo and in vitro. We showed that when autophagy is impaired, ER-mediated protection is lost. We further demonstrated that autophagy inhibits caspase activation and apoptosis. Based on our findings, we conclude that autophagy is required for the neuroprotection mediated by mild ER stress, and therefore ER preconditioning has potential therapeutic value for the treatment of neurodegenerative diseases. PMID:22660271

  20. Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor.

    PubMed

    Omi, T; Tanimukai, H; Kanayama, D; Sakagami, Y; Tagami, S; Okochi, M; Morihara, T; Sato, M; Yanagida, K; Kitasyoji, A; Hara, H; Imaizumi, K; Maurice, T; Chevallier, N; Marchal, S; Takeda, M; Kudo, T

    2014-01-01

    We recently demonstrated that endoplasmic reticulum (ER) stress induces sigma-1 receptor (Sig-1R) expression through the PERK pathway, which is one of the cell's responses to ER stress. In addition, it has been demonstrated that induction of Sig-1R can repress cell death signaling. Fluvoxamine (Flv) is a selective serotonin reuptake inhibitor (SSRI) with a high affinity for Sig-1R. In the present study, we show that treatment of neuroblastoma cells with Flv induces Sig-1R expression by increasing ATF4 translation directly, through its own activation, without involvement of the PERK pathway. The Flv-mediated induction of Sig-1R prevents neuronal cell death resulting from ER stress. Moreover, Flv-induced ER stress resistance reduces the infarct area in mice after focal cerebral ischemia. Thus, Flv, which is used frequently in clinical practice, can alleviate ER stress. This suggests that Flv could be a feasible therapy for cerebral diseases caused by ER stress. PMID:25032855

  1. Validation of ERS-1 environmental data products

    NASA Technical Reports Server (NTRS)

    Goodberlet, Mark A.; Swift, Calvin T.; Wilkerson, John C.

    1994-01-01

    Evaluation of the launch-version algorithms used by the European Space Agency (ESA) to derive wind field and ocean wave estimates from measurements of sensors aboard the European Remote Sensing satellite, ERS-1, has been accomplished through comparison of the derived parameters with coincident measurements made by 24 open ocean buoys maintained by the National Oceanic and Atmospheric Administration). During the period from November 1, 1991 through February 28, 1992, data bases with 577 and 485 pairs of coincident sensor/buoy wind and wave measurements were collected for the Active Microwave Instrument (AMI) and Radar Altimeter (RA) respectively. Based on these data, algorithm retrieval accuracy is estimated to be plus or minus 4 m/s for AMI wind speed, plus or minus 3 m/s for RA wind speed and plus or minus 0.6 m for RA wave height. After removing 180 degree ambiguity errors, the AMI wind direction retrieval accuracy was estimated at plus or minus 28 degrees. All of the ERS-1 wind and wave retrievals are relatively unbiased. These results should be viewed as interim since improved algorithms are under development. As final versions are implemented, additional assessments should be conducted to complete the validation.

  2. June 1997 ER-2 Flight Measurements

    NASA Technical Reports Server (NTRS)

    Jones, Irby W.

    2003-01-01

    Within our current understanding of the atmospheric ionizing radiation, the ER-2 flight package was designed to provide a complete characterization of the physical fields and evaluate various dosimetric techniques for routine monitoring. A flight plan was developed to sample the full dynamic range of the atmospheric environment especially at altitudes relevant to the development of the High Speed Civil Transport. The flight of the instruments occurred in June of 1997 where predictive models indicated a maximum in the high altitude radiation environment occurring approximately nine months after the minimum in the solar sunspot cycle. The flights originated at Moffett field at the Ames Research Center on ER-2 aircraft designated as 706. The equipment was shipped mid- May 1997 for unpacking and checkout, size fitting, systems functional test, and preflight testing on aircraft power with flight readiness achieved on May 30, 1997. The equipment was qualified on its first engineering flight on June 2, 1997 and the subsequent science gathering flights followed during the period of June 5-15, 1997. Herein we give an account of the flight operations.

  3. ER stress-induced autophagy in melanoma.

    PubMed

    Meng, Xiao-Xiao; Yao, Mu; Zhang, Xu Dong; Xu, Hong-Xi; Dong, Qihan

    2015-08-01

    The activation of RAF-MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade by v-raf murine sarcoma viral oncogene homolog B1 (BRAF)(V600E) mutation is a key alteration in melanoma. Although BRAF inhibitor (BRAFi) has achieved remarkable clinical success, the positive response to BRAFi is not sustainable, and the initial clinical benefit is eventually barred by the development of resistance to BRAFi. There is growing evidence to suggest that endoplasmic reticulum (ER) stress-induced autophagy could be a potential pro-survival mechanism that contributes to genesis of melanoma and to the resistance to BRAFi. ER stress-induced autophagy is an evolutionarily conserved membrane process. By degrading and recycling proteins and organelles via the formation of autophagous vesicles and their fusion with lysosomes, the autophagy plays a key role in homeostasis as well as pathological processes. In this review, we examine the autophagy phenomenon in melanocytic nevus, primary and metastatic melanoma, and its significance in BRAFi-resistant melanoma. PMID:26096022

  4. Magnetic properties of ErN films

    NASA Astrophysics Data System (ADS)

    Meyer, C.; Ruck, B. J.; Preston, A. R. H.; Granville, S.; Williams, G. V. M.; Trodahl, H. J.

    2010-07-01

    We report a magnetization study of stoichiometric ErN nanocrystalline films grown on Si and protected by a GaN passivating layer. According to the temperature dependence of the resistivity the films are heavily doped semiconductors. Above 100 K the magnetization data fit well to a Curie-Weiss behavior with a moment expected within the free-ion ErJ={15}/{2} multiplet. Below 50 K the Curie-Weiss plot steepens to an effective moment corresponding to that in the crystal-field determined quartet ground state, and develops a clear paramagnetic Curie-Weiss temperature of about 4.5 K. Zero-field- and field-cooled magnetization curves and the AC susceptibility firmly establish a ferromagnetic ground state within that multiplet below a Curie temperature of 6.30.7 K. Due to the (1 1 1) texture of the film the comparison between the magnetization behavior, when the field is applied parallel and perpendicular to the film plane, gives new information about the magnetic structure. An arrangement of the moments according to the model derived from neutron diffraction for bulk HoN is strongly suggested.

  5. Cyclopia Extracts Act as ER? Antagonists and ER? Agonists, In Vitro and In Vivo

    PubMed Central

    Visser, Koch; Mortimer, Morn; Louw, Ann

    2013-01-01

    Hormone replacement therapy associated risks, and the concomitant reluctance of usage, has instigated the search for new generations of estrogen analogues that would maintain estrogen benefits without associated risks. Furthermore, if these analogues display chemo-preventative properties in breast and endometrial tissues it would be of great value. Both the selective estrogen receptor modulators as well as the selective estrogen receptor subtype modulators have been proposed as estrogen analogues with improved risk profiles. Phytoestrogen containing extracts of Cyclopia, an indigenous South African fynbos plant used to prepare Honeybush tea may serve as a source of new estrogen analogues. In this study three extracts, P104, SM6Met, and cup-of-tea, from two species of Cyclopia, C. genistoides and C. subternata, were evaluated for ER subtype specific agonism and antagonism both in transactivation and transrepression. For transactivation, the Cyclopia extracts displayed ER? antagonism and ER? agonism when ER subtypes were expressed separately, however, when co-expressed only agonism was uniformly observed. In contrast, for transrepression, this uniform behavior was lost, with some extracts (P104) displaying uniform agonism, while others (SM6Met) displayed antagonism when subtypes were expressed separately and agonism when co-expressed. In addition, breast cancer cell proliferation assays indicate that extracts antagonize cell proliferation in the presence of estrogen at lower concentrations than that required for proliferation. Furthermore, lack of uterine growth and delayed vaginal opening in an immature rat uterotrophic model validates the ER? antagonism of extracts observed in vitro and supports the potential of the Cyclopia extracts as a source of estrogen analogues with a reduced risk profile. PMID:24223909

  6. ER-associated degradation: Protein quality control and beyond

    PubMed Central

    Ruggiano, Annamaria; Foresti, Ombretta

    2014-01-01

    Even with the assistance of many cellular factors, a significant fraction of newly synthesized proteins ends up misfolded. Cells evolved protein quality control systems to ensure that these potentially toxic species are detected and eliminated. The best characterized of these pathways, the ER-associated protein degradation (ERAD), monitors the folding of membrane and secretory proteins whose biogenesis takes place in the endoplasmic reticulum (ER). There is also increasing evidence that ERAD controls other ER-related functions through regulated degradation of certain folded ER proteins, further highlighting the role of ERAD in cellular homeostasis. PMID:24637321

  7. Role of ER-?36 in breast cancer by typical xenoestrogens.

    PubMed

    Liu, Jun; Xu, Zhixiang; Ma, Xiaodong; Huang, Bin; Pan, Xuejun

    2015-09-01

    About 10 years have passed since the discovery of the estrogen receptor subtype, estrogen receptor alpha 36 (ER-?36). The relationship between cancerous cells and ER-?36 in mediating xenoestrogens (XEs) is a significant issue in the progression and treatment of breast cancer. XEs can combine with classical estrogen receptors and other receptor subtypes especially ER-?36, resulting in activation of nongenomic pathways as well as genomic pathways. Recently, most laboratories have focused on further study into the rapidly nongenomic mechanisms by overexpressing or knocking down ER-?36 in breast cancer cell lines. These rapid responses can induce the deregulation of cell cycle, and then lead to the abnormal proliferation and differentiation by regulating distinct downstream pathways. It appears that ER-?36 is a key factor in increasing risk of breast cancer. However, in several recent studies, the action mechanisms of ER-?36 by XEs in breast cancer cell lines are not always clear. In this review, we firstly summarize the expression pattern and tumor biology of ER-?36, then discuss these related estrogenic effects of ER-?36, and lastly give the predictive and prognostic value of ER-?36 as diagnostic marker by mediating typical XEs in breast cancer. PMID:26337277

  8. Ire1 supports normal ER differentiation in developing Drosophila photoreceptors.

    PubMed

    Xu, Zuyuan; Chikka, Madhusudana Rao; Xia, Hongai; Ready, Donald F

    2016-03-01

    The endoplasmic reticulum (ER) serves virtually all aspects of cell physiology and, by pathways that are incompletely understood, is dynamically remodeled to meet changing cell needs. Inositol-requiring enzyme 1 (Ire1), a conserved core protein of the unfolded protein response (UPR), participates in ER remodeling and is particularly required during the differentiation of cells devoted to intense secretory activity, so-called 'professional' secretory cells. Here, we characterize the role of Ire1 in ER differentiation in the developing Drosophila compound eye photoreceptors (R cells). As part of normal development, R cells take a turn as professional secretory cells with a massive secretory effort that builds the photosensitive membrane organelle, the rhabdomere. We find rough ER sheets proliferate as rhabdomere biogenesis culminates, and Ire1 is required for normal ER differentiation. Ire1 is active early in R cell development and is required in anticipation of peak biosynthesis. Without Ire1, the amount of rough ER sheets is strongly reduced and the extensive cortical ER network at the rhabdomere base, the subrhabdomere cisterna (SRC), fails. Instead, ER proliferates in persistent and ribosome-poor tubular tangles. A phase of Ire1 activity early in R cell development thus shapes dynamic ER. PMID:26787744

  9. ER? localization influenced outcomes of EGFR-TKI treatment in NSCLC patients with EGFR mutations

    PubMed Central

    Wang, Zhijie; Li, Zhenxiang; Ding, Xiaosheng; Shen, Zhirong; Liu, Zhentao; An, Tongtong; Duan, Jianchun; Zhong, Jia; Wu, Meina; Zhao, Jun; Zhuo, Minglei; Wang, Yuyan; Wang, Shuhang; Sun, Yu; Bai, Hua; Wang, Jie

    2015-01-01

    Effects of estrogen receptor? (ER?) localization on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) are unknown. First, we analyzed the relationship between ER? localization determined by immunohistochemistry and EGFR-TKI outcomes in 184 patients with advanced NSCLC and found that ER? expression localized in the cytoplasm and/or nucleus. The frequency of cytoplasmic ER? (c-ER?) and nuclear ER? (n-ER?) co-expression was 12% (22/184). C-ER? and n-ER? co-expression was correlated with poor median progression-free survival compared to patients without co-expression. In subsequent in vitro experiments, PC9 cells transfected with ER? isoform1 (ER?1, strong expression of both c-ER? and n-ER?) were more resistant to gefitinib than PC9 cells transfected with ER? isoform2 or 5 (ER?2 or ER?5, strong expression of ER? in cytoplasm but not nucleus). Resistance was identified due to interactions between ER?1 and other isoforms, and mediated by activation of non-genomic pathways. Moreover, gefitinib resistance was reversed by a combination treatment with gefitinib and fulvestrant, both in cell lines and in one NSCLC patient. These results suggested that c-ER? and n-ER? co-expression was a potential molecular indicator of EGFR-TKI resistance, which might be overcome by combining EGFR-TKI and ER antagonist. PMID:26096604

  10. Ltc1 is an ER-localized sterol transporter and a component of ERmitochondria and ERvacuole contacts

    PubMed Central

    Murley, Andrew; Sarsam, Reta D.; Toulmay, Alexandre; Yamada, Justin; Prinz, William A.

    2015-01-01

    Organelle contact sites perform fundamental functions in cells, including lipid and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics approach in yeast, we identified new ERmitochondria and ERvacuole contacts specified by an uncharacterized protein, Ylr072w. Ylr072w is a conserved protein with GRAM and VASt domains that selectively transports sterols and is thus termed Ltc1, for Lipid transfer at contact site 1. Ltc1 localized to ERmitochondria and ERvacuole contacts via the mitochondrial import receptors Tom70/71 and the vacuolar protein Vac8, respectively. At mitochondria, Ltc1 was required for cell viability in the absence of Mdm34, a subunit of the ERmitochondria encounter structure. At vacuoles, Ltc1 was required for sterol-enriched membrane domain formation in response to stress. Increasing the proportion of Ltc1 at vacuoles was sufficient to induce sterol-enriched vacuolar domains without stress. Thus, our data support a model in which Ltc1 is a sterol-dependent regulator of organelle and cellular homeostasis via its dual localization to ERmitochondria and ERvacuole contact sites. PMID:25987606

  11. 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

  12. Measuring IGF-1, ER-? and EGFR expression can predict tamoxifen-resistance in ER-positive breast cancer.

    PubMed

    Chong, Kelvin; Subramanian, Ashok; Sharma, Anup; Mokbel, Kefah

    2011-01-01

    In vitro studies have suggested that tamoxifen resistance may be due to altered expression and downstream signalling of insulin-like growth factor-1 (IGF-1) receptor (IGF-1l), oestrogen receptor-alpha (ER?), epidermal growth factor receptor (EGFR) and HER-2. We investigated which gene expressions could predict tamoxifen resistant breast cancer. Expression of IGF-1R, IGF-1 ligand (IGF-1), ER?, EGFR and HER-2 in 91 ER-positive breast cancer tumours were measured using real-time PCR and correlated with clinical outcome. The tamoxifen resistant group (n=20) consisted of: i) tumours which were resistant to neoadjuvant tamoxifen treatment and ii) tumours which were excised from patients who later developed recurrence or metastasis during adjuvant tamoxifen treatment. These were compared with tamoxifen sensitive tumours which were surgical excision specimens from patients who did not develop recurrence/metastasis during adjuvant tamoxifen treatment. Tumours with higher IGF-1 ligand and ER? expression took longer to develop tamoxifen resistance. Tamoxifen resistant tumours had lower IGF-1 and ER? expression compared to tamoxifen-sensitive tumours. IGF-1 expression strongly correlated with ER? expression in the tamoxifen sensitive group only. ER? inversely correlated with EGFR expression in the tamoxifen resistant group only. We conclude that IGF-1 ligand and ER? expression in breast carcinomas can be measured to predict tamoxifen resistance. Measuring ER? expression using RT-PCR may be more sensitive than immunohistochemistry in determining anti-oestrogen sensitivity. PMID:21273576

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

    PubMed

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

    2015-12-01

    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

  14. 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

  15. Spectroscopy of the Er-doped lithium tetraborate glasses

    NASA Astrophysics Data System (ADS)

    Padlyak, B. V.; Lisiecki, R.; Ryba-Romanowski, W.

    2016-04-01

    The electron paramagnetic resonance (EPR), optical absorption, and luminescence (emission and excitation) spectra as well as luminescence kinetics of the Er-doped glasses with Li2B4O7 composition were investigated and analysed. The high optical quality glasses with Li2B4O7:Er composition containing 0.5 and 1.0 mol.% Er2O3 were obtained from corresponding polycrystalline compound by standard glass synthesis. The EPR spectroscopy in the 4.2-300 K temperature range and optical spectroscopy at 300 K show that the Er impurity is incorporated into the network of Li2B4O7 glass as Er3+ (4f11, 4I15/2) ions, exclusively. The local structure of the Er3+ luminescence centres in Li sites of the glass network is proposed. Based on the standard Judd-Ofelt theory the oscillator strength (Pcal) and experimental oscillator strength (Pexp) for observed absorption transitions as well as phenomenological intensity parameters (Ω2, Ω4, Ω6) for Er3+ centres in the Li2B4O7:Er glass containing 1.0 mol.% Er2O3 were calculated. Spectroscopic parameters of relevance for laser applications, including emission probabilities of transitions (Wr), branching ratios (β), and radiative lifetime (τrad) have been calculated for main observed emission transitions of the Er3+ centres in Li2B4O7:Er glasses. Experimental and calculated lifetimes were compared and quantum efficiency (η) for green (4S3/2 → 4I15/2 transition) and infrared (4I13/2 → 4I15/2 transition) emission bands has been estimated.

  16. ER Stress and ?-Cell Pathogenesis of Type 1 and Type 2 Diabetes and Islet Transplantation

    PubMed Central

    Kataoka, Hitomi Usui; Noguchi, Hirofumi

    2013-01-01

    Endoplasmic reticulum (ER) stress affects the pathogenesis of diabetes. ER stress plays important roles, both in type 1 and type 2 diabetes, because pancreatic ?-cells possess highly developed ER for insulin secretion. This review summarizes the relationship between ER stress and the pathogenesis of type 1 and type 2 diabetes. In addition, the association between islet transplantation and ER stress is discussed.

  17. The ERS-1 radar altimeter: An overview

    NASA Astrophysics Data System (ADS)

    Francis, C. R.

    1984-08-01

    The ERS-1 (ESA) radar altimeter implementation, parameter estimation, autocalibration, data flow, and operating principles are summarized. The microwave subsystem contains an ultrastable oscillator and a chirp generator. A traveling wave tube amplifier and its electronic power conditioner form the high power amplifier (the radar transmitter output). The signal processor subassembly has a spectrum analyzer and a microcomputer. The microcomputer also handles real time parameter estimation, with center of gravity tracking in the ice mode and suboptimal maximum likelihood estimation (SMLE) in the ocean mode. The curve-fitting SMLE is used in calibrating the signal path of the instrument to a precision of 0.7 nsec. Command and housekeeping data use an S band telemetry link, scientific data are delivered via X band, in real time and as a dump.

  18. Final Technical Report for Award # ER64999

    SciTech Connect

    Metcalf, William W.

    2014-10-08

    This report provides a summary of activities for Award # ER64999, a Genomes to Life Project funded by the Office of Science, Basic Energy Research. The project was entitled "Methanogenic archaea and the global carbon cycle: a systems biology approach to the study of Methanosarcina species". The long-term goal of this multi-investigator project was the creation of integrated, multiscale models that accurately and quantitatively predict the role of Methanosarcina species in the global carbon cycle under dynamic environmental conditions. To achieve these goals we pursed four specific aims: (1) genome sequencing of numerous members of the Order Methanosarcinales, (2) identification of genomic sources of phenotypic variation through in silico comparative genomics, (3) elucidation of the transcriptional networks of two Methanosarcina species, and (4) development of comprehensive metabolic network models for characterized strains to address the question of how metabolic models scale with genetic distance.

  19. The homocysteine-inducible endoplasmic reticulum (ER) stress protein Herp counteracts mutant α-synuclein-induced ER stress via the homeostatic regulation of ER-resident calcium release channel proteins.

    PubMed

    Belal, Cherine; Ameli, Neema J; El Kommos, Adam; Bezalel, Spencer; Al'Khafaji, Aziz M; Mughal, Mohamed R; Mattson, Mark P; Kyriazis, George A; Tyrberg, Björn; Chan, Sic L

    2012-03-01

    Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases. The mechanisms that lead to ER stress and whereby ER stress contributes to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies. Here we show that knockdown of Herp (Homocysteine-inducible ER stress protein), an ER stress-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death induced by mutant α-synuclein (αSyn) that causes an inherited form of Parkinson's disease (PD). Functionally, Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels. Deletion of the UBL domain or pharmacological inhibition of proteasomes abolishes the Herp-mediated stabilization of ER Ca(2+) homeostasis. Furthermore, knockdown or pharmacological inhibition of ER Ca(2+) release channels ameliorates ER stress, suggesting that impaired homeostatic regulation of Ca(2+) channels promotes a protracted ER stress with the consequent activation of ER stress-associated apoptotic pathways. Interestingly, sustained upregulation of ER stress markers and aberrant accumulation of ER Ca(2+) release channels were detected in transgenic mutant A53T-αSyn mice. Collectively, these data establish a causative link between impaired ER Ca(2+) homeostasis and chronic ER stress in the degenerative cascades induced by mutant αSyn and suggest that Herp is essential for the resolution of ER stress through maintenance of ER Ca(2+) homeostasis. Our findings suggest a therapeutic potential in PD for agents that increase Herp levels or its ER Ca(2+)-stabilizing action. PMID:22045699

  20. The homocysteine-inducible endoplasmic reticulum (ER) stress protein Herp counteracts mutant α-synuclein-induced ER stress via the homeostatic regulation of ER-resident calcium release channel proteins

    PubMed Central

    Belal, Cherine; Ameli, Neema J.; El Kommos, Adam; Bezalel, Spencer; Al'Khafaji, Aziz M.; Mughal, Mohamed R.; Mattson, Mark P.; Kyriazis, George A.; Tyrberg, Björn; Chan, Sic L.

    2012-01-01

    Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases. The mechanisms that lead to ER stress and whereby ER stress contributes to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies. Here we show that knockdown of Herp (Homocysteine-inducible ER stress protein), an ER stress-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death induced by mutant α-synuclein (αSyn) that causes an inherited form of Parkinson's disease (PD). Functionally, Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca2+ release channels. Deletion of the UBL domain or pharmacological inhibition of proteasomes abolishes the Herp-mediated stabilization of ER Ca2+ homeostasis. Furthermore, knockdown or pharmacological inhibition of ER Ca2+ release channels ameliorates ER stress, suggesting that impaired homeostatic regulation of Ca2+ channels promotes a protracted ER stress with the consequent activation of ER stress-associated apoptotic pathways. Interestingly, sustained upregulation of ER stress markers and aberrant accumulation of ER Ca2+ release channels were detected in transgenic mutant A53T-αSyn mice. Collectively, these data establish a causative link between impaired ER Ca2+ homeostasis and chronic ER stress in the degenerative cascades induced by mutant αSyn and suggest that Herp is essential for the resolution of ER stress through maintenance of ER Ca2+ homeostasis. Our findings suggest a therapeutic potential in PD for agents that increase Herp levels or its ER Ca2+-stabilizing action. PMID:22045699

  1. The intersection of Golgi-ER retrograde and autophagic trafficking

    PubMed Central

    He, Shanshan; OConnell, Douglas; Zhang, Xiaowei; Yang, Yongfei; Liang, Chengyu

    2013-01-01

    For decades, a marvelous amount of work has been performed to identify molecules that regulate distinct stages of membrane transport in the ER-Golgi secretory pathway and autophagy, which are implicated in many human diseases. However, an important missing piece in this puzzle is how the cell dynamically coordinates these crisscrossed trafficking pathways in response to different stimuli. Our recent study has identified UVRAG as a mode-switching protein that coordinates Golgi-ER retrograde and autophagic trafficking. UVRAG recognizes phosphatidylinositol-3-phosphate (PtdIns3P) and locates to the ER, where it couples the ER tethering complex containing RINT1 to govern Golgi-ER retrograde transport. Intriguingly, when autophagy is induced, UVRAG undergoes a partnering shift from the ER tethering complex to the BECN1 autophagy complex, resulting in concomitant inhibition of Golgi-ER transport and the activation of ATG9 autophagic trafficking. Therefore, Golgi-ER retrograde and autophagy-related membrane trafficking are functionally interdependent and tightly regulated by UVRAG to ensure spatiotemporal fidelity of protein transport and organelle homeostasis, providing distinguished insights into trafficking-related diseases. PMID:24246972

  2. Reaction Diffusion Modeling of Calcium Dynamics with Realistic ER Geometry

    PubMed Central

    Means, Shawn; Smith, Alexander J.; Shepherd, Jason; Shadid, John; Fowler, John; Wojcikiewicz, Richard J. H.; Mazel, Tomas; Smith, Gregory D.; Wilson, Bridget S.

    2006-01-01

    We describe a finite-element model of mast cell calcium dynamics that incorporates the endoplasmic reticulum's complex geometry. The model is built upon a three-dimensional reconstruction of the endoplasmic reticulum (ER) from an electron tomographic tilt series. Tetrahedral meshes provide volumetric representations of the ER lumen, ER membrane, cytoplasm, and plasma membrane. The reaction-diffusion model simultaneously tracks changes in cytoplasmic and ER intraluminal calcium concentrations and includes luminal and cytoplasmic protein buffers. Transport fluxes via PMCA, SERCA, ER leakage, and Type II IP3 receptors are also represented. Unique features of the model include stochastic behavior of IP3 receptor calcium channels and comparisons of channel open times when diffusely distributed or aggregated in clusters on the ER surface. Simulations show that IP3R channels in close proximity modulate activity of their neighbors through local Ca2+ feedback effects. Cytoplasmic calcium levels rise higher, and ER luminal calcium concentrations drop lower, after IP3-mediated release from receptors in the diffuse configuration. Simulation results also suggest that the buffering capacity of the ER, and not restricted diffusion, is the predominant factor influencing average luminal calcium concentrations. PMID:16617072

  3. CW YVO4:Er Laser with Resonant Pumping

    NASA Astrophysics Data System (ADS)

    Gorbachenya, K. N.; Kisel, V. E.; Yasukevich, A. S.; Matrosov, V. N.; Tolstik, N. A.; Kuleshov, N. V.

    2015-05-01

    The lasing characteristics of a YVO4:Er laser with resonant pumping in the 1.5-1.6 μm range are studied. Lasing is obtained at λ = 1603 nm with a differential efficiency of up to 61%. YVO4:Er crystals are found to offer promise for use in efficient resonantly (in-band) pumped lasers.

  4. How to Avoid the ER If You Have Asthma

    MedlinePLUS

    ... How to Avoid the ER if You Have Asthma KidsHealth > For Teens > How to Avoid the ER if You Have Asthma Print A A A Text Size What's in ... is the last resort for someone who has asthma. If a flare-up is really out of ...

  5. Epithelial ER Stress in Crohn's Disease and Ulcerative Colitis.

    PubMed

    Cao, Stewart S

    2016-04-01

    Research in the past decade has greatly expanded our understanding of the pathogenesis of inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. In addition to the sophisticated network of immune response, the epithelial layer lining the mucosa has emerged as an essential player in the development and persistence of intestinal inflammation. As the frontline of numerous environmental insults in the gut, the intestinal epithelial cells are subject to various cellular stresses. In eukaryotic cells, disturbance of endoplasmic reticulum homeostasis may lead to the accumulation of unfolded and misfolded proteins in the ER lumen, a condition called ER stress. This cellular process activates the unfolded protein response, which functions to enhance the ER protein folding capacity, alleviates the burden of protein synthesis and maturation, and activates ER-associated protein degradation. Paneth and goblet cells, 2 secretory epithelial populations in the gut, are particularly sensitive to ER stress on environmental or genetic disturbances. Recent studies suggested that epithelial ER stress may contribute to the pathogenesis of Crohn's disease and ulcerative colitis by compromising protein secretion, inducing epithelial cell apoptosis and activating proinflammatory response in the gut. Our knowledge of ER stress in intestinal epithelial function may open avenue to new inflammatory bowel disease therapies by targeting the ER protein folding homeostasis in the cells lining the intestinal mucosa. PMID:26950312

  6. Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications.

    PubMed

    Meeran, Syed M; Patel, Shweta N; Li, Yuanyuan; Shukla, Samriddhi; Tollefsbol, Trygve O

    2012-01-01

    Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ER? expression for effective treatment of ER?-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ER?-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ER? expression. The combination of 20 g/mL GTPs and 5 M SFN was found to be the optimal dose of ER?-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ER? expression was consistently correlated with ER? promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ER? promoter revealed that GTPs and SFN altered the binding of ER?-transcriptional co-repressor complex thereby contributing to ER?-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens. PMID:22662208

  7. Bioactive Dietary Supplements Reactivate ER Expression in ER-Negative Breast Cancer Cells by Active Chromatin Modifications

    PubMed Central

    Meeran, Syed M.; Patel, Shweta N.; Li, Yuanyuan; Shukla, Samriddhi; Tollefsbol, Trygve O.

    2012-01-01

    Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ER? expression for effective treatment of ER?-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ER?-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ER? expression. The combination of 20 g/mL GTPs and 5 M SFN was found to be the optimal dose of ER?-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ER? expression was consistently correlated with ER? promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ER? promoter revealed that GTPs and SFN altered the binding of ER?-transcriptional co-repressor complex thereby contributing to ER?-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens. PMID:22662208

  8. Search and destroy: ER quality control and ER-associated protein degradation.

    PubMed

    Sayeed, Ayaz; Ng, Davis T W

    2005-01-01

    Proteins synthesized in the endoplasmic reticulum (ER) encounter quality control checkpoints that verify their fitness to proceed in the secretory pathway. Molecules undergoing folding and assembly are kept out of the exocytic pathway until maturation is complete. Misfolded side products that inevitably form are removed from the mixture of conformers and returned to the cytosol for degradation. How unfolded proteins are recognized and how irreversibly misfolded proteins are sorted to ER-associated degradation pathways was poorly understood. Recent developments from a combination of genetic and biochemical analyses has revealed new insights into these mechanisms. The emerging view shows distinct pathways working in collaboration to filter the diverse range of unfolded proteins from the transport flow and to divert misfolded molecules for destruction. PMID:15814429

  9. Apoptosis/Necrosis Induction by Ultraviolet, in ER Positive and ER Negative Breast Cancer Cell Lines

    PubMed Central

    Shokrollahi Barough, Mahdieh; Hasanzadeh, Hadi; Barati, Mehdi; Pak, Fatemeh; Kokhaei, Parviz; Rezaei-Tavirani, Mostafa

    2015-01-01

    Background: Ultraviolet (UV) light exposure has been one of the major inducers of apoptosis. UV exposure has caused pyrimidine dimers and DNA fragmentation which might lead to cell cycle arrest and apoptosis signals activation. UV induced apoptosis has investigated in MDA-MB 468 as an ER negative breast adenocarcinoma and MCF-7 as an ER positive breast cancer cell line. Apoptosis induction rate by UV might be different in these two types of cells due to different biological characteristics of the cell. Objectives: In this paper we have evaluated serial dose of UV-B exposure on ER positive and ER negative breast cancer cell lines and its effect on apoptosis or necrosis induction in these cells. Materials and Methods: MDA-MB468 and MCF-7 cell lines have cultured for 24 hours and UV exposure has carried out at 290 nm at dose of 154 J/m2 to 18 KJ/m2 using UV lamp. UV exposed cells have incubated in cell culture condition for 24 or 48 hours following UV exposure and the cells have stained and analyzed by flow cytometry for apoptosis evaluation by Annexin V/PI method. Results: Apoptosis rate (PI and Annexin V double positive cells) after 24 hours incubation was higher in 24 hours in comparison with 48 hours incubation in both cell lines. The frequency of PI positive MDA-MB 468 cells was higher than PI and Annexin V double positive cells after 48 hours. PI positive MDA-MB 468 cells were significantly higher than MCF-7 cells in 24 hours incubation time. Conclusions: The results have shown that MDA-MB 468 cells were more sensitive to UV exposure and DNA fragmentation and necrosis pathway was dominant in these cells. PMID:26855725

  10. ER-2 Observations of Precipitation Systems During TRMM-LBA

    NASA Technical Reports Server (NTRS)

    Heymsfield, Gerald; Tian, Lin; Geerts, Bart

    1999-01-01

    The NASA ER-2 performed numerous flights over precipitation systems in Rondonia, Brazil. The ER-2 carried a payload including the ER-2 Doppler Radar (EDOP), the Advanced Microwave Precipitation Radiometer (AMPR), the Lightning Instrument Package, and other instruments. This presentation will overview the types of data sets collected during TRMM-LBA (Tropical Rainfall Measuring Mission Satellite-Large Scale Biosphere Atmosphere Experiment in Amazonia) with particular emphasis on EDOP measurements. Numerous cases of convection ranging from weak to very intense, were overflown by the ER-2. Two TRMM overpasses were coincident with ER-2 flights which allowed for intercomparisons between the Precipitation Radiometer (PR), EDOP, and the S-POL (S-band Polarimetric Radar) and TOGA (Tropical Oceans and Global Atmosphere) ground-based radars. Preliminary results from this comparison will be presented as well as initial selection of case studies and efforts involving vertical motions in convection.

  11. ER-2 Observations of Precipitation Systems During TRMM-LBA

    NASA Technical Reports Server (NTRS)

    Heymsfield, Gerald; Tian, Lin; Geerts, Bart

    1999-01-01

    The NASA ER-2 performed numerous flights over precipitation systems in Rondonia, Brazil. The ER-2 carried a payload including the ER-2 Doppler Radar (EDOP), the Advanced Microwave Precipitation Radiometer (AMPR), the Lightning Instrument Package, and other instruments. This presentation will overview the types of data sets collected during TRMM-LBA with particular emphasis on EDOP measurements. Numerous cases of convection ranging from weak to very intense, were overflown by the ER-2. Two TRMM overpasses were coincident with ER-2 flights which allowed for intercomparisons between the Precipitation Radiometer (PR), EDOP, and the S-POL and TOGA ground-based radars. Preliminary results from this comparison will be presented as well as initial selection of case studies and efforts involving vertical motions in convection.

  12. Linking ER Stress to Autophagy: Potential Implications for Cancer Therapy

    PubMed Central

    Verfaillie, Tom; Salazar, Maria; Velasco, Guillermo; Agostinis, Patrizia

    2010-01-01

    Different physiological and pathological conditions can perturb protein folding in the endoplasmic reticulum, leading to a condition known as ER stress. ER stress activates a complex intracellular signal transduction pathway, called unfolded protein response (UPR). The UPR is tailored essentially to reestablish ER homeostasis also through adaptive mechanisms involving the stimulation of autophagy. However, when persistent, ER stress can switch the cytoprotective functions of UPR and autophagy into cell death promoting mechanisms. Recently, a variety of anticancer therapies have been linked to the induction of ER stress in cancer cells, suggesting that strategies devised to stimulate its prodeath function or block its prosurvival function, could be envisaged to improve their tumoricidial action. A better understanding of the molecular mechanisms that determine the final outcome of UPR and autophagy activation by chemotherapeutic agents, will offer new opportunities to improve existing cancer therapies as well as unravel novel targets for cancer treatment. PMID:20145727

  13. Thirty Years of ER Conferences: Milestones, Achievements, and Future Directions

    NASA Astrophysics Data System (ADS)

    Chen, Peter P.

    This paper describes the milestones/achievements in the past 30 years and the future directions for the Entity-Relationship (ER) Conferences or the Conceptual Modeling Conferences. The first ER Conference was held in 1979 in Los Angeles. The major milestones and achievements of the ER Conferences are stated. Several interesting points about the ER Conferences are pointed out including: (1) it is one of the few longest running IT conference series, (2) It is not a conference sponsored directly by a major IT professional societies such as ACM or IEEE, (3) It does not depend on the financial support of a major IT professional society or a commercial company, (4) It maintains very high quality standards for papers and presentations. The reasons for the successes of the ER Conferences are analyzed. Suggestions for its continued successes are presented.

  14. FOXK2 Transcription Factor Suppresses ER?-positive Breast Cancer Cell Growth Through Down-Regulating the Stability of ER? via mechanism involving BRCA1/BARD1

    PubMed Central

    Liu, Ying; Ao, Xiang; Jia, Zhaojun; Bai, Xiao-Yan; Xu, Zhaowei; Hu, Gaolei; Jiang, Xiao; Chen, Min; Wu, Huijian

    2015-01-01

    Estrogen receptors (ERs) are critical regulators of breast cancer development. Identification of molecules that regulate the function of ERs may facilitate the development of more effective breast cancer treatment strategies. In this study, we showed that the forkhead transcription factor FOXK2 interacted with ER?, and inhibited ER?-regulated transcriptional activities by enhancing the ubiquitin-mediated degradation of ER?. This process involved the interaction between FOXK2 and BRCA1/BARD1, the E3 ubiquitin ligase of ER?. FOXK2 interacted with BARD1 and acted as a scaffold protein for BRCA1/BARD1 and ER?, leading to enhanced degradation of ER?, which eventually accounted for its decreased transcriptional activity. Consistent with these observations, overexpression of FOXK2 inhibited the transcriptional activity of ER?, decreased the transcription of ER? target genes, and suppressed the proliferation of ER?-positive breast cancer cells. In contract, knockdown of FOXK2 in MCF-7 cells promoted cell proliferation. However, when ER? was also knocked down, knockdown of FOXK2 had no effect on cell proliferation. These findings suggested that FOXK2 might act as a negative regulator of ER?, and its association with both ER? and BRCA1/BARD1 could lead to the down-regulation of ER? transcriptional activity, effectively regulating the function of ER?. PMID:25740706

  15. Structure-activity relationships of bisphenol A analogs at estrogen receptors (ERs): discovery of an ER?-selective antagonist.

    PubMed

    Maruyama, Keisuke; Nakamura, Masaharu; Tomoshige, Shusuke; Sugita, Kazuyuki; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

    2013-07-15

    Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ER?/ER? subtype selectivity. Among the compounds examined, 18 was found to be a potent ER?-antagonist with high selectivity over ER? and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ER?. ER?-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. PMID:23768907

  16. Blocking translocation of cell surface molecules from the ER to the cell surface by intracellular antibodies targeted to the ER

    PubMed Central

    Bldicke, Thomas

    2007-01-01

    Abstract Intracellular antibodies (intrabodies) constitute a potent tool to neutralize the function of target proteins inside specific cell compartments (cytosol, nucleus, mitochondria and ER). The intrabody technology is an attractive alternative to the generation of gene-targeted knockout animals and complements or replaces knockdown techniques such as antisense-RNA, RNAi and RNA aptamers. This article focuses on intrabodies targeted to the ER. Intracellular anti-bodies expressed and retained inside the ER (ER intrabodies) are shown to be highly efficient in blocking the translocation of secreted and cell surface molecules from the ER to the cell surface.The advantage of ER intrabodies over cytoplasmic intrabodies is that they are correctly folded and easier to select. A particular advantage of the intrabody technology over existing ones is the possibility of inhibiting selectively post-translational modifications of proteins.The main applications of ER intrabodies so far have been (i) inactivation of oncogenic receptors and (ii) functional inhibition of virus envelope proteins and virus-receptor molecules on the surface of host cells.In cancer research, the number of in vivo mouse models for evaluation of the therapeutic potential of intrabodies is increasing.In the future, endosomal localized receptors involved in bacterial and viral infections, intracellular oncogenic receptors and enzymes involved in glycosylation of tumour antigens might be new targets for ER intrabodies. PMID:17367501

  17. Expression of ER?, ER? and Co-Regulator PELP1/MNAR in Colorectal Cancer: Prognostic Significance and Clinicopathologic Correlations

    PubMed Central

    Grivas, Petros D.; Tzelepi, Vassiliki; Sotiropoulou-Bonikou, Georgia; Kefalopoulou, Zinovia; Papavassiliou, Athanasios G.; Kalofonos, Haralabos

    2009-01-01

    Background: Estrogen receptor ? (ER?) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. ER novel co-regulator, proline-, glutamic acid- and leucine-rich protein 1 (PELP1/MNAR) has been characterized, but its expression in colorectal carcinomas has not been investigated. Methods: ER?, ER? and PELP1/MNAR protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas and adenocarcinomas from 113 patients with colorectal cancer. Results: ER? expression is extremely rare in colorectal tissue and its expression does not appear to be associated with colorectal carcinogenesis. ER? and PELP1/MNAR were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells and myofibroblasts. When intensity of staining was taken into account, the expression of both proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. ER? expression in epithelial cells was correlated with decreased disease progression free survival. PELP1/MNAR overexpression in epithelial cells was found to be an independent favorable prognostic factor. Additionally, the expression of both proteins was significantly increased in stromal myofibroblasts of carcinomas compared to adenomas and normal mucosa. Conclusion: ER? and PELP1/MNAR appear to be involved in colorectal tumorigenesis and might have prognostic significance. PMID:19478391

  18. Up Conversion Measurements in Er:YAG; Comparison with 1.6 Micrometer Laser Performance

    NASA Technical Reports Server (NTRS)

    Barnes, Norman P.; Walsh, Brian M.; Amzajerdian, Farzin; Reichle, Donald J.; Busch, George E.; Carrion, William A.

    2011-01-01

    Up conversion significantly affects Er:YAG lasers. Measurements performed here for low Er concentration are significantly different than reported high Er concentration. The results obtained here are used to predict laser performance and are compared with experimental results.

  19. Synthetic embryonic lethality upon deletion of the ER cochaperone p58IPK and the ER stress sensor ATF6α

    PubMed Central

    Gomez, Javier A.; Tyra, Heather M.; McCabe, Diane DeZwaan; Olivier, Alicia K.; Rutkowski, D. Thomas

    2014-01-01

    The unfolded protein response (UPR) is activated as a consequence of alterations to ER homeostasis. It upregulates a group of ER chaperones and cochaperones, as well as other genes that improve protein processing within the secretory pathway. The UPR effector ATF6α augments—but is not essential for—maximal induction of ER chaperones during stress, yet its role, if any, in protecting cellular function during normal development and physiology is unknown. A systematic analysis of multiple tissues from Atf6α−/− mice revealed that all tissues examined were grossly insensitive to loss of ATF6α. However, combined deletion of ATF6α and the ER cochaperone p58IPK resulted in synthetic embryonic lethality. These findings reveal for the first time that an intact UPR can compensate for the genetic impairment of protein folding in the ER in vivo. The also expose a role for p58IPK in normal embryonic development. PMID:24275136

  20. Er3+ diffusion in LiTaO3 crystal

    NASA Astrophysics Data System (ADS)

    Zhang, De-Long; Zhang, Qun; Wong, Wing-Han; Pun, Edwin Yue-Bun

    2015-12-01

    Some Er3+-doped LiTaO3 plates were prepared by in-diffusion of Er-metal film locally coated onto congruent Z-cut substrate in air at a wide temperature range from 1000 to 1500 °C. After diffusion, Er3+-doping effect on LiTaO3 refractive index and Li2O out-diffusion arising from Er3+ in-diffusion were studied at first. Refractive indices at the doped and undoped surface parts were measured by prism coupling technique and the surface composition was estimated. The results show that Er3+ dopant has small contribution to the LiTaO3 index. Li2O out-diffusion is slight (Li2O content loss <0.3 mol%) for the temperature below 1300 °C while is moderate (Li2O content loss <0.6 mol%) for the temperature above 1400 °C. The Er3+ profile was studied by secondary ion mass spectrometry. The study shows that the diffused Er3+ ions follow either a complementary error function or a Gaussian profile. Characteristic parameters including diffusivity, diffusion constant, activation energy, solubility, solubility constant and heat of solution were obtained and compared with the LiNbO3 case. The comparison shows that the diffusivity and solubility in LiTaO3 are considerably smaller than in LiNbO3 because of the difference of Ta and Nb in atomic weight.

  1. EPR studies of the mechanochemically Er3+-activated fluorite nanoparticles

    NASA Astrophysics Data System (ADS)

    Irisova, I. A.; Rodionov, A. A.; Tayurskii, D. A.; Yusupov, R. V.

    2011-10-01

    In the present work we show with EPR spectroscopy that the simultaneous grinding of the crystalline CaF2 and ErF3 salts leads to the mechanochemical doping of the single Er3+ ions in the CaF2 host. Dependence of the EPR spectra intensity on the grain size indicates clearly that the Er3+ centers are created at the surface of the particles. Dominant part of the observed paramagnetic centers represent the Er3+ ions substituting the regular quasicubic Ca2+ lattice site (g = 6.7) perturbed by the vicinity of the surface. Fine particles of CaF2 reveal also the nearly-isotropic EPR signal at g ~ 1.97 that originates from the surface defects and can be used for characterization of the obtained samples with respect of the average grain size. Grinding of the of the CaF2 and ErF3 mixture in the ratio of 100:1 during 12 hours gives the surface density of the Er3+ ions of ~ 0.1 nm-2, or ~ 104 Er3- ions per the 190-nm size particle.

  2. Structure and Dynamics of ER: Minimal Networks and Biophysical Constraints

    PubMed Central

    Lin, Congping; Zhang, Yiwei; Sparkes, Imogen; Ashwin, Peter

    2014-01-01

    The endoplasmic reticulum (ER) in live cells is a highly mobile network whose structure dynamically changes on a number of timescales. The role of such drastic changes in any system is unclear, although there are correlations with ER function. A better understanding of the fundamental biophysical constraints on the system will allow biologists to determine the effects of molecular factors on ER dynamics. Previous studies have identified potential static elements that the ER may remodel around. Here, we use these structural elements to assess biophysical principles behind the network dynamics. By analyzing imaging data of tobacco leaf epidermal cells under two different conditions, i.e., native state (control) and latrunculin B (treated), we show that the geometric structure and dynamics of ER networks can be understood in terms of minimal networks. Our results show that the ER network is well modeled as a locally minimal-length network between the static elements that potentially anchor the ER to the cell cortex over longer timescales; this network is perturbed by a mixture of random and deterministic forces. The network need not have globally minimum length; we observe cases where the local topology may change dynamically between different Euclidean Steiner network topologies. The networks in the treated cells are easier to quantify, because they are less dynamic (the treatment suppresses actin dynamics), but the same general features are found in control cells. Using a Langevin approach, we model the dynamics of the nonpersistent nodes and use this to show that the images can be used to estimate both local viscoelastic behavior of the cytoplasm and filament tension in the ER network. This means we can explain several aspects of the ER geometry in terms of biophysical principles. PMID:25099815

  3. ER to synapse trafficking of NMDA receptors

    PubMed Central

    Horak, Martin; Petralia, Ronald S.; Kaniakova, Martina; Sans, Nathalie

    2014-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. There are three distinct subtypes of ionotropic glutamate receptors (GluRs) that have been identified including 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptors (AMPARs), N-methyl-D-aspartate receptors (NMDARs) and kainate receptors. The most common GluRs in mature synapses are AMPARs that mediate the fast excitatory neurotransmission and NMDARs that mediate the slow excitatory neurotransmission. There have been large numbers of recent reports studying how a single neuron regulates synaptic numbers and types of AMPARs and NMDARs. Our current research is centered primarily on NMDARs and, therefore, we will focus in this review on recent knowledge of molecular mechanisms occurring (1) early in the biosynthetic pathway of NMDARs, (2) in the transport of NMDARs after their release from the endoplasmic reticulum (ER); and (3) at the plasma membrane including excitatory synapses. Because a growing body of evidence also indicates that abnormalities in NMDAR functioning are associated with a number of human psychiatric and neurological diseases, this review together with other chapters in this issue may help to enhance research and to gain further knowledge of normal synaptic physiology as well as of the etiology of many human brain diseases. PMID:25505872

  4. Characterization of the Ers Regulon of Enterococcus faecalis▿

    PubMed Central

    Riboulet-Bisson, Eliette; Sanguinetti, Maurizio; Budin-Verneuil, Aurélie; Auffray, Yanick; Hartke, Axel; Giard, Jean-Christophe

    2008-01-01

    Ers has been qualified as the PrfA-like transcriptional regulator of Enterococcus faecalis. In a previous study we reported that Ers is important for the survival within macrophages of this opportunist pathogenic bacterium. In the present work we have used proteomic and microarray expression profiling of E. faecalis JH2-2 and an ers-deleted mutant (Δers mutant) strains to define the Ers regulon. In addition to EF_0082 (encoding a putative facilitator family transporter), already known to be under Ers regulation, three genes or operons displayed a significant decrease (confirmed by reverse transcription quantitative PCR) in expression in the Δers mutant. The first locus corresponds to three genes: arcA, arcB, and arcC1 (arcABC). These genes are members of the ADI operon, encoding enzymes of the arginine deiminase system. The second is the EF_1459 gene, which encodes a hypothetical protein and is located within a putative phage genetic element. Lastly, Ef_3319 is annotated as the alpha subunit of the citrate lyase encoded by citF. citF is a member of a putative 12-gene operon involved in citrate catabolism. Moreover, the promoter sequence, similar to the “PrfA box” and found in the promoter regions of ers and EF_0082, has been shown to be included in the DNA segment recognized by Ers. Phenotypic analysis of the Δers mutant strain revealed a growth defect when cultured with arginine or citrate as the energy source; this was not seen for the wild type. As expected, similar results were obtained with mutants in which arcA and citF were inactivated. In addition, in the mouse peritonitis model of virulence, the Δers mutant appeared significantly less lethal than the JH2-2 wild-type strain. Taken together, these results indicate that the regulator Ers has a pleiotropic effect, especially in the cellular metabolism and virulence of E. faecalis. PMID:18426870

  5. Harvard ER-2 OH laser-induced fluorescence instrument

    NASA Technical Reports Server (NTRS)

    Wennberg, Paul O.; Anderson, James G.

    1994-01-01

    The Harvard ER-2 OH instrument is scheduled to be integrated into the NASA ER-2 high altitude aircraft ozone payload in August 1992. Design and fabrication is presently underway. This experiment is a descendant of a balloon borne instrument designed and built in the mid-1980s. The ER-2 instrument is being designed to measure OH and HO2 as part of the NASA ozone payload for the investigation of processes controlling the concentration of stratospheric ozone. Although not specifically designed to do so, it is hoped that valid measurements of OH and HO2 can be made in the remote free troposphere with this instrument.

  6. Photoluminescence enhancement of Er-doped silica containing Ge nanoclusters

    NASA Astrophysics Data System (ADS)

    Guzman, J.; Shin, S. J.; Liao, C. Y.; Yuan, C. W.; Stone, P. R.; Dubón, O. D.; Yu, K. M.; Beeman, J. W.; Watanabe, M.; Ager, J. W.; Chrzan, D. C.; Haller, E. E.

    2009-11-01

    The photoluminescence (PL) of Er-doped silica films containing Ge nanoclusters synthesized by ion implantation was investigated. The area of the 1540 nm Er3+ PL peak was enhanced by up to a factor of 200 by the addition of Ge nanoclusters. The PL enhancement was found to be proportional to the concentration of Ge atoms. Control experiments with argon ion implantation were used to show that the enhancement is due to the presence of Ge and not radiation damage. Furthermore, the Er3+ PL was found to be strongly influenced by the postgrowth annealing and the crystallinity of the Ge nanoclusters.

  7. Inhibitors of Protein Translocation Across the ER Membrane.

    PubMed

    Kalies, Kai-Uwe; Rmisch, Karin

    2015-10-01

    Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is particularly critical in fast-growing tumour cells. Thus, the process can serve as target both for potential cancer drugs and for bacterial virulence factors. Inhibitors of protein transport across the ER membrane range from broad-spectrum to highly substrate-specific and can interfere with virtually any stage of this multistep process, and even with transport of endocytosed antigens into the cytosol for cross-presentation. PMID:26122014

  8. Arctic geodynamics: Arctic science and ERS-1 satellite altimetry

    NASA Technical Reports Server (NTRS)

    Anderson, Allen Joel; Sandwell, David T.

    1994-01-01

    A detailed gravity field map of the mid Arctic Ocean, spreading ridge system was produced on the basis of ERS-1 satellite altimetry data. Areas of special concern, the Barents and Kara Seas, and areas surrounding the islands of Svalbard, Frans Josef Land and Novoya Zemlya are reviewed. ERS-1 altimetry covers unique Arctic and Antarctic latitudes above 72 degrees. Before ERS-1 it was not possible to study these areas with satellite altimetry. Gravity field solutions for the Barents Sea, portions of the Arctic Ocean and the Norwegian sea are shown. The largest gravity anomalies occur along the Greenland fracture zone as well as along transform faults near Svalbard.

  9. Concentration dependence of upconversion emission from Er:YAG fibers.

    PubMed

    Sharp, J H; Shi, P C W; Watson, I A

    2012-11-15

    Fibers of Er:YAG have been grown using the laser-heated pedestal growth method. Fibers with Er concentrations ranging from 0.5 to 10 mol. % have been produced and excitation at 965 nm has been used to produce intense upconversion emission at green and red wavelengths. The dependence of ground state absorption and upconversion emission on dopant concentration has been studied and shown to exhibit lower levels of self-absorption than previously reported. At Er concentrations of 5 mol. % and above; however, the variation of upconversion emission intensity with pump power deviates from theoretical predictions, exhibiting saturation behavior consistent with concentration quenching. PMID:23164850

  10. Absorption and photoluminescence properties of Er-doped and Er/Yb codoped soda-silicate laser glasses

    SciTech Connect

    Li, S.F.; Zhang, Q.Y.; Lee, Y.P.

    2004-11-01

    Er-doped and Er/Yb codoped soda-silicate laser glasses with various concentrations of Er and Yb were fabricated. The absorption and the photoluminescence (PL) spectra were measured and analyzed. For the Er- doped soda-slilicate glasses, the optimum Er concentration for the PL intensity at 1536 nm turns out to be 0.5 at. %, and the full width at half maximum (FWHM) of PL spectrum increases from 18 to 26 nm, with the increase of the concentration from 0.1 to 0.8 at. %. The PL intensity of Er/Yb codoped soda-silicate glasses with an Er concentration of 0.5 at. % is enhanced approximately by four times, and the optimum Yb concentration for the PL intensity at 1536 nm is analyzed to be 3.0 at. %. The PL spectrum becomes broader with increasing the Yb concentration, up to a FWHM of 80 nm at 6.0 at. %. Yb. The relation between the absorption and PL spectra, together with the mechanism of PL broadening, has also been addressed.

  11. 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

  12. Electron spin resonance study of Er-concentration effect in GaAs;Er,O containing charge carriers

    SciTech Connect

    Elmasry, F.; Okubo, S.; Ohta, H.; Fujiwara, Y.

    2014-05-21

    Er-concentration effect in GaAs;Er,O containing charge carriers (n-type, high resistance, p-type) has been studied by X-band Electron spin resonance (ESR) at low temperature (4.7?K?Er,O without carrier. The local structure around Er-2O centers is not affected by carriers because similar angular dependence of g-values was observed in both cases (with/without carrier). For temperature dependence, linewidth and lineshape analysis suggested the existence of Er dimers with antiferromagnetic exchange interaction of about 7?K. Moreover, drastic decrease of ESR intensity for C signal in p-type sample was observed and it correlates with the decrease of photoluminescence (PL) intensity. Possible model for the Er-2O trap level in GaAs:Er,O is discussed from the ESR and PL experimental results.

  13. Return of Collective Rotation in {sup 157}Er and {sup 158}Er at Ultrahigh Spin

    SciTech Connect

    Paul, E. S.; Twin, P. J.; Evans, A. O.; Choy, P. T. W.; Nolan, P. J.; Pipidis, A.; Riley, M. A.; Campbell, D. B.; Simpson, J.; Appelbe, D. E.; Joss, D. T.; Clark, R. M.; Cromaz, M.; Fallon, P.; Goergen, A.; Lee, I. Y.; Macchiavelli, A. O.; Ward, D.; Ragnarsson, I.

    2007-01-05

    A new frontier of discrete-line {gamma}-ray spectroscopy at ultrahigh spin has been opened in the rare-earth nuclei {sup 157,158}Er. Four rotational structures, displaying high moments of inertia, have been identified, which extend up to spin {approx}65({Dirac_h}/2{pi}) and bypass the band-terminating states in these nuclei which occur at {approx}45({Dirac_h}/2{pi}). Cranked Nilsson-Strutinsky calculations suggest that these structures arise from well-deformed triaxial configurations that lie in a valley of favored shell energy which also includes the triaxial strongly deformed bands in {sup 161-167}Lu.

  14. Growth and spectroscopic properties of Er 3+ single doped and Er 3+-Yb 3+ co-doped YAl 3(BO 3) 4 crystals

    NASA Astrophysics Data System (ADS)

    You, Weixiong; Lin, Yanfu; Chen, Yujin; Luo, Zundu; Huang, Yidong

    2004-10-01

    Er3+-doped and Er3+-Yb3+ co-doped yttrium aluminum borate (YAB) single crystals have been grown by the top-seeded solution growth method using a new flux system, namely NaF-MoO3-B2O3. The Er3+ concentrations were 1.3 mol% for both single doped and co-doped crystals and the Yb3+ concentration in the Er3+-Yb3+ co-doped crystal was 20.0 mol% in the raw materials. The distribution coefficients of Er3+ single doped and Er3+-Yb3+ co-doped crystals were measured. The polarized absorption and fluorescence spectra of Er3+-Yb3+ co-doped crystal were recorded and compared with those of Er3+ single doped crystal. The results demonstrate that Er3+-Yb3+ co-doped YAB crystal is a potential candidate for 1.55 μm laser materials.

  15. ER Dysfunction and Protein Folding Stress in ALS

    PubMed Central

    Matus, Soledad; Valenzuela, Vicente; Medinas, Danilo B.; Hetz, Claudio

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is the most frequent paralytic disease in adults. Most ALS cases are considered sporadic with no clear genetic component. The disruption of protein homeostasis due to chronic stress responses at the endoplasmic reticulum (ER) and the accumulation of abnormal protein inclusions are extensively described in ALS mouse models and patient-derived tissue. Recent studies using pharmacological and genetic manipulation of the unfolded protein response (UPR), an adaptive reaction against ER stress, have demonstrated a complex involvement of the pathway in experimental models of ALS. In addition, quantitative changes in ER stress-responsive chaperones in body fluids have been proposed as possible biomarkers to monitor the disease progression. Here we review most recent advances attributing a causal role of ER stress in ALS. PMID:24324498

  16. UPR, autophagy and mitochondria crosstalk underlies the ER stress response

    PubMed Central

    Senft, Daniela; Ronai, Zeev A.

    2015-01-01

    Cellular stress, induced by external or internal cues, activates several well-orchestrated processes aimed at either restoring cellular homeostasis or committing to cell death. Those processes include the unfolded protein response (UPR), autophagy, hypoxia, and mitochondrial function, which are part of the global ER stress (ERS) response. When one of the ERS elements is impaired, as often occurs under pathological conditions, overall cellular homeostasis may be perturbed. Further, activation of the UPR could trigger changes in mitochondrial function or autophagy, which could modulate the UPR, exemplifying cross-talk processes. Among the numerous factors that control the magnitude or duration of these processes are ubiquitin ligases, which govern overall cellular stress outcomes. Here we summarize crosstalk among fundamental processes governing ERS responses. PMID:25656104

  17. ER Dysfunction and Protein Folding Stress in ALS.

    PubMed

    Matus, Soledad; Valenzuela, Vicente; Medinas, Danilo B; Hetz, Claudio

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is the most frequent paralytic disease in adults. Most ALS cases are considered sporadic with no clear genetic component. The disruption of protein homeostasis due to chronic stress responses at the endoplasmic reticulum (ER) and the accumulation of abnormal protein inclusions are extensively described in ALS mouse models and patient-derived tissue. Recent studies using pharmacological and genetic manipulation of the unfolded protein response (UPR), an adaptive reaction against ER stress, have demonstrated a complex involvement of the pathway in experimental models of ALS. In addition, quantitative changes in ER stress-responsive chaperones in body fluids have been proposed as possible biomarkers to monitor the disease progression. Here we review most recent advances attributing a causal role of ER stress in ALS. PMID:24324498

  18. Magnetic behavior of nanocrystalline ErCo(2).

    PubMed

    Das, Sitikantha D; Mohapatra, Niharika; Iyer, Kartik K; Bapat, R D; Sampathkumaran, E V

    2009-07-22

    We have investigated the magnetic behavior of the nanocrystalline form of a well-known Laves phase compound, ErCo(2)-the bulk form of which has been known to undergo an interesting first-order ferrimagnetic ordering near 32K-synthesized by high-energy ball-milling. It is found that, in these nanocrystallites, Co exhibits ferromagnetic order at room temperature, as inferred from the magnetization data. However, the magnetic transition temperature for the Er sub-lattice remains essentially unaffected suggesting the (Er)4f-Co(3d) coupling is weak on Er magnetism. The net magnetic moment as measured at high fields, for example at 120kOe, is significantly reduced with respect to that for the bulk in the ferrimagnetically ordered state and possible reasons are outlined for this. We have also compared the magnetocaloric behavior for the bulk and for nanoparticles. PMID:21828543

  19. Neuronal ER Stress in Axon Injury and Neurodegeneration

    PubMed Central

    Li, Shaohua; Yang, Liu; Selzer, Michael E.; Hu, Yang

    2014-01-01

    Injuries to CNS axons result not only in Wallerian degeneration of the axon distal to the injury, but also in death or atrophy of the axotomized neurons, depending on injury location and neuron type. No method of permanently avoiding these changes has been found, despite extensive knowledge concerning mechanisms of secondary neuronal injury. The autonomous endoplasmic reticulum (ER) stress pathway in neurons has recently been implicated in retrograde neuronal degeneration. In addition to the emerging role of ER morphology in axon maintenance, we propose that ER stress is a common neuronal response to disturbances in axon integrity and a general mechanism for neurodegeneration. Thus manipulation of the ER stress pathway could have important therapeutic implications for neuroprotection. PMID:23955583

  20. The Grand Banks ERS-1 SAR wave spectra validation experiment

    NASA Technical Reports Server (NTRS)

    Vachon, P. W.; Dobson, F. W.; Smith, S. D.; Anderson, R. J.; Buckley, J. R.; Allingham, M.; Vandemark, D.; Walsh, E. J.; Khandekar, M.; Lalbeharry, R.

    1993-01-01

    As part of the ERS-1 validation program, the ERS-1 Synthetic Aperture Radar (SAR) wave spectra validation experiment was carried out over the Grand Banks of Newfoundland (Canada) in Nov. 1991. The principal objective of the experiment was to obtain complete sets of wind and wave data from a variety of calibrated instruments to validate SAR measurements of ocean wave spectra. The field program activities are described and the rather complex wind and wave conditions which were observed are summarized. Spectral comparisons with ERS-1 SAR image spectra are provided. The ERS-1 SAR is shown to have measured swell and range traveling wind seas, but did not measure azimuth traveling wind seas at any time during the experiment. Results of velocity bunching forward mapping and new measurements of the relationship between wind stress and sea state are also shown.

  1. Kids' ER Visits for Medicine Overdoses Dropping: Report

    MedlinePLUS

    ... news/fullstory_154521.html Kids' ER Visits for Medicine Overdoses Dropping: Report Education, prevention messages, safer packaging ... of emergency room visits involved ingestion of one medicine. Nearly half involved prescription pills, tablets or capsules. ...

  2. Measuring the Digital Divide with PingER

    SciTech Connect

    Cottrell, L.

    2003-10-01

    We introduce the PingER project/toolkit and show its relevance to monitoring sites in developing countries. We then show results from PingER that illustrate the extent of the Digital Divide in terms of Internet performance between developed and developing regions, which developing regions are catching up, keeping up, or falling behind and the magnitude of the differences in performance between developed regions and developing regions.

  3. [Er:YAG laser: tissue interaction and histomorphological characterization].

    PubMed

    Palmieri, B; Capone, S; Rottigni, V

    2011-01-01

    Authors describe Er:YAG laser interaction with tissues, in particular their histomorphological characteristics to identify a specific clinic area for laser application through the examination of different clinical international trials. This study includes experimental trials about pig and rat skin laser application to know laser Er: YAG capability and limits; investigation is extended to laser application in human soft tissues as mucosa, periosteum and bones, its utility in cutaneous pathologies and in antiageing treatments. PMID:22041807

  4. ER stress induces NLRP3 inflammasome activation and hepatocyte death

    PubMed Central

    Lebeaupin, C; Proics, E; de Bieville, C H D; Rousseau, D; Bonnafous, S; Patouraux, S; Adam, G; Lavallard, V J; Rovere, C; Le Thuc, O; Saint-Paul, M C; Anty, R; Schneck, A S; Iannelli, A; Gugenheim, J; Tran, A; Gual, P; Bailly-Maitre, B

    2015-01-01

    The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases. PMID:26355342

  5. Genetically engineered ER?-positive breast cancer mouse models.

    PubMed

    Dabydeen, Sarah A; Furth, Priscilla A

    2014-06-01

    The majority of human breast cancers are estrogen receptor-positive (ER+), but this has proven challenging to model in genetically engineered mice. This review summarizes information on 21 mouse models that develop ER+ mammary cancer. Where available, information on cancer pathology and gene expression profiles is referenced to assist in understanding which histological subtype of ER+ human cancer each model might represent. ESR1, CCDN1, prolactin, TGF?, AIB1, ESPL1, and WNT1 overexpression, PIK3CA gain of function, as well as loss of P53 (Trp53) or STAT1 are associated with ER+ mammary cancer. Treatment with the PPAR? agonist efatutazone in a mouse with Brca1 and p53 deficiency and 7,12-dimethylbenz(a)anthracene exposure in combination with an activated myristoylated form of AKT1 also induce ER+ mammary cancer. A spontaneous mutant in nude mice that develops metastatic ER+ mammary cancer is included. Age of cancer development ranges from 3 to 26 months and the percentage of cancers that are ER+ vary from 21 to 100%. Not all models are characterized as to their estrogen dependency and/or response to anti-hormonal therapy. Strain backgrounds include C57Bl/6, FVB, BALB/c, 129S6/SvEv, CB6F1, and NIH nude. Most models have only been studied on one strain background. In summary, while a range of models are available for studies of pathogenesis and therapy of ER+ breast cancers, many could benefit from further characterization, and opportunity for development of new models remains. PMID:24481326

  6. Memantine ER/Donepezil: A Review in Alzheimer's Disease.

    PubMed

    Greig, Sarah L

    2015-11-01

    A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10mg (Namzaric) is available in the USA for patients with moderate to severe Alzheimer's disease (AD) on stable memantine and donepezil therapy. The fixed-dose formulation is bioequivalent to coadministration of the individual drugs. In a 24-week, phase III trial in patients with moderate to severe AD, addition of memantine ER 28mg once daily to stable cholinesterase inhibitor (ChEI) therapy was more effective than add-on placebo on measures of cognition, global clinical status, dementia behaviour and semantic processing ability, although between-group differences on a measure of daily function did not significantly differ. In subgroup analyses in donepezil-treated patients, add-on memantine ER was more effective than add-on placebo on measures of cognition, dementia behaviour and semantic processing, although there were no significant between-group differences on measures of global clinical status and daily function. Memantine ER plus ChEI combination therapy was generally well tolerated in the phase III trial, with diarrhoea, dizziness and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients. Thus, memantine ER plus donepezil combination therapy is an effective and well tolerated treatment option for patients with moderate to severe AD. The fixed-dose combination is potentially more convenient than coadministration of the individual agents. PMID:26519339

  7. Functional and morphological impact of ER stress on mitochondria.

    PubMed

    Vannuvel, Kayleen; Renard, Patricia; Raes, Martine; Arnould, Thierry

    2013-09-01

    Over the past years, knowledge and evidence about the existence of crosstalks between cellular organelles and their potential effects on survival or cell death have been constantly growing. More recently, evidence accumulated showing an intimate relationship between endoplasmic reticulum (ER) and mitochondria. These close contacts not only establish extensive physical links allowing exchange of lipids and calcium but they can also coordinate pathways involved in cell life and death. It is now obvious that ER dysfunction/stress and unfolded protein response (UPR) as well as mitochondria play major roles in apoptosis. However, while the effects of major ER stress on cell death have been largely studied and reviewed, it becomes more and more evident that cells might regularly deal with sublethal ER stress, a condition that does not necessarily lead to cell death but might affect the function/activity of other organelles such as mitochondria. In this review, we will particularly focus on these new, interesting and intriguing metabolic and morphological events that occur during the early adaptative phase of the ER stress, before the onset of cell death, and that remain largely unknown. Relevance and implication of these mitochondrial changes in response to ER stress conditions for human diseases such as type II diabetes and Alzheimer's disease will also be considered. PMID:23629871

  8. Lockheed ER-2 #806 high altitude research aircraft during landing

    NASA Technical Reports Server (NTRS)

    1998-01-01

    ER-2 tail number 806, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  9. Lockheed ER-2 #809 high altitude research aircraft in flight

    NASA Technical Reports Server (NTRS)

    1999-01-01

    ER-2 tail number 809, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  10. Lockheed ER-2 high altitude research aircraft in flight

    NASA Technical Reports Server (NTRS)

    1997-01-01

    ER-2 tail number 706, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  11. Lockheed ER-2 #806 high altitude research aircraft in flight

    NASA Technical Reports Server (NTRS)

    1998-01-01

    ER-2 tail number 806, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  12. Lockheed ER-2 #809 high altitude research aircraft in flight

    NASA Technical Reports Server (NTRS)

    1998-01-01

    ER-2 tail number 809, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  13. Oceanographic results from analysis of ERS-1 altimetry

    NASA Technical Reports Server (NTRS)

    Tapley, B. D.; Shum, C. K.; Chambers, D. P.; Peterson, G. E.; Ries, J. C.

    1994-01-01

    Large scale dynamic ocean topography and its variations were observed using ERS-1 radar altimeter measurements. The altimeter measurements analyzed are primarily from the ESA ocean product (OPR02) and from the Interim Geophysical Data Records (IGDR) generated by NOAA from the fast delivery (FD) data during the ERS-1 35 day repeat orbit phase. The precise orbits used for the dynamic topography solution are computed using dual satellite crossover measurements from ERS-1 and TOPEX (Topology Ocean Experiment)/Poseidon (T/P) as additional tracking data, and using improved models and constants which are consistent with T/P. Analysis of the ERS-1 dynamic topography solution indicates agreement with the T/P solution at the 5 cm root mean square level, with regional differences as large as 15 cm tide gauges at the 8 to 9 cm level. There are differences between the ERS-1 OPR02 and IGDR determined dynamic topography solutions on the order of 5 cm root mean square. Mesoscale oceanic variability time series obtained using collinear analysis of the ERS-1 altimeter data show good qualitative agreement when compared with the T/P results.

  14. Physiological ER Stress Mediates the Differentiation of Fibroblasts

    PubMed Central

    Taniguchi, Manabu; Shingaki, Kenta; Kubo, Tateki; Kiya, Koichiro; Fujiwara, Toshihiro; Kanazawa, Shigeyuki; Kanematsu, Ryutaro; Maeda, Tameyasu; Takamura, Hironori; Yamada, Kohe; Miyoshi, Ko; Hosokawa, Ko; Tohyama, Masaya; Katayama, Taiichi

    2015-01-01

    Recently, accumulating reports have suggested the importance of endoplasmic reticulum (ER) stress signaling in the differentiation of several tissues and cells, including myoblasts and osteoblasts. Secretory cells are easily subjected to ER stress during maturation of their secreted proteins. Skin fibroblasts produce and release several proteins, such as collagens, matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs) and glycosaminoglycans (GAGs), and the production of these proteins is increased at wound sites. Differentiation of fibroblasts into myofibroblasts is one of the key factors for wound healing and that TGF-? can induce fibroblast differentiation into myofibroblasts, which express ?-smooth muscle actin. Well-differentiated myofibroblasts show increased production of collagen and TGF-?, and bring about wound healing. In this study, we examined the effects of ER stress signaling on the differentiation of fibroblasts, which is required for wound healing, using constitutively ER stress-activated primary cultured fibroblasts. The cells expressed positive ?-smooth muscle actin signals without TGF-? stimulation compared with control fibroblasts. Gel-contraction assays suggested that ER stress-treated primary fibroblasts caused stronger shrinkage of collagen gels than control cells. These results suggest that ER stress signaling could accelerate the differentiation of fibroblasts to myofibroblasts at injured sites. The present findings may provide important insights for developing therapies to improve wound healing. PMID:25928708

  15. Laser performance of in-band pumped Er : LiYF4 and Er : LiLuF4 crystals

    NASA Astrophysics Data System (ADS)

    Gorbachenya, K. N.; Kurilchik, S. V.; Kisel, V. E.; Yasukevich, A. S.; Kuleshov, N. V.; Nizamutdinov, A. S.; Korableva, S. L.; Semashko, V. V.

    2016-02-01

    Spectroscopic properties of Er : LiLuF4 and Er : LiYF4 crystals in the spectral region near 1.5 μm and the lasing characteristics of these crystals under in-band pumping at a wavelength of 1522 nm are studied. With the Er : LiLuF4 crystal, the maximum slope efficiency with respect to the absorbed pump power was 44% at a wavelength of 1609 nm. Continuous-wave operation of an inband pumped Er : LiYF4 laser is obtained for the first time. The output power at a wavelength of 1606 nm was 58 mW with a slope efficiency of 21%.

  16. Long Term Assessment of ERS-1 and ERS-2 Wind and Wave Products Using ERA-Interim

    NASA Astrophysics Data System (ADS)

    Aballa, Saleh; Hersbach, Hans; Bidlot, Jean-Raymond

    2010-12-01

    The ERS mission is a great opportunity for the meteorological and ocean-wave communities. In particular, the wind and wave products from both ERS-1 and ERS-2 provide an invaluable data set. The quality of the fast delivery (FD) products of scatterometer wind (UWI), SAR Wave Mode (UWA) and radar altimeter wind and wave (URA) and the off- line OPR (Ocean Product) altimeter wind and wave products were already assessed against the consistent ECMWF 40-Year Reanalysis (ERA-40) wind fields and presented by Hersbach et al. [1]. The recent availability of the higher quality ECMWF interim reanalysis (ERA- Interim) motivated us to repeat the same exercise to get a better evaluation of the quality of ERS wind and wave products.

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

    SciTech Connect

    Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi; Kawai, Kazuhiro; Hashiguchi, Teruto; Maruyama, Ikuro; Kanekura, Takuro

    2010-06-25

    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 10 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.

  18. Preparation and optical properties of YH2:Er2+ and Y2O3:Er3+ nanoparticles.

    PubMed

    Liu, Tong; Cao, Yurong; Zhu, Mu; Zhang, Tongwen; Zheng, Jie; Li, Xingguo

    2013-06-01

    The rare earth hydride nanoparticles have been prepared successfully by a novel method of hydrogen plasma-metal reaction. The YH2:Er2+ nanoparticles of 40-50 nm were polycrystalline and in hexagonal shape. The Y2O3:Er3+ nanoparticles were fabricated by annealing the hydride nanoparticles in air at 300, 500 and 700 degrees C, respectively. The influence of the sintering temperature on the size, crystal structure and optical properties of these nanoparticle samples were investigated. After annealing, the Y2O3:Er3+ nanoparticles became single crystalline and spherical shape, and the mean particle size of these particles did not change apparently upon the annealing temperature up to 700 degrees C. With the increase of the annealing temperature, the absorption intensity of YH2 in the Fourier transform infrared spectroscopy spectra decreased and the peak position moved to high-frequency, whereas the absorption intensity of Y2O3 was enhanced. The intensity of the near-IR fluorescence spectra of the Y2O3:Er3+ nanoparticles increased remarkably with the increase of the annealing temperature from 300 to 700 degrees C. The Y2O3:Er3+ sample sintered at 700 degrees C exhibited a strong photoluminescent intensity at the wavelength of about 1535 nm, with a narrow full width of 6 nm at the half maximum. This makes the Y2O3:Er3+ nanoparticles promising for the applications in the optical communication devices. PMID:23862433

  19. Bond strength of composites on Er:YAG and Er,Cr:YSGG laser-irradiated enamel

    NASA Astrophysics Data System (ADS)

    Apel, Christian; Gutknecht, Norbert

    1999-02-01

    In an in vitro study the bond strength of composite materials on Er:YAG and Er,Cr:YSGG laser-radiated enamel was examined. The results achieved on enamel surfaces conditioned conventionally using the acid etching method served as a control. On 80 extracted cariesfree third molars an enamel area of 4 X 4 mm was conditioned with three different systems. The Er:YAG laser was used at pulse frequencies of 8 Hz, 10 Hz, 12 Hz and 15 Hz using an energy of 120 mJ at each setting. The Er,Cr:YSGG laser was used at the settings of 20 Hz/50 mJ, 20 Hz/100 mJ and 20 Hz/150 mJ. The repetition rate for this device is constantly 20 Hz. In the reference group 10 teeth were etched with 37% phosphoric acid. In order to be able to perform the tensile tests under standard conditions metal brackets were placed on the conditioned surfaces. The 'Orthodontic-Bonding-System' was used as an adhesive system. The brackets were pulled off from the etched surfaces vertically to the tooth using a tensile testing machine. The results confirmed the highest bond strengths in the group of enamel surfaces which have been conditioned with acid etching gel. The bond strength of the Er:YAG laser (8, 10 and 12 Hz)- and Er,Cr:YSGG laser (20 Hz/150 mJ)-conditioned enamel surfaces was not significantly lower.

  20. Organisation of human ER-exit sites: requirements for the localisation of Sec16 to transitional ER

    PubMed Central

    Hughes, Helen; Budnik, Annika; Schmidt, Katy; Palmer, Krysten J.; Mantell, Judith; Noakes, Chris; Johnson, Andrew; Carter, Deborah A.; Verkade, Paul; Watson, Peter; Stephens, David J.

    2009-01-01

    Summary The COPII complex mediates the selective incorporation of secretory cargo and relevant machinery into budding vesicles at specialised sites on the endoplasmic reticulum membrane called transitional ER (tER). Here, we show using confocal microscopy, immunogold labelling of ultrathin cryosections and electron tomography that in human cells at steady state, Sec16 localises to cup-like structures of tER that are spatially distinct from the localisation of other COPII coat components. We show that Sec16 defines the tER, whereas Sec23-Sec24 and Sec13-Sec31 define later structures that precede but are distinct from the intermediate compartment. Steady-state localisation of Sec16 is independent of the localisation of downstream COPII components Sec23-Sec24 and Sec13-Sec31. Sec16 cycles on and off the membrane at a slower rate than other COPII components with a greater immobile fraction. We define the region of Sec16A that dictates its robust localisation of tER membranes and find that this requires both a highly charged region as well as a central domain that shows high sequence identity between species. The central conserved domain of Sec16 binds to Sec13 linking tER membrane localisation with COPII vesicle formation. These data are consistent with a model where Sec16 acts as a platform for COPII assembly at ERES. PMID:19638414

  1. Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER inBudding Vesicles.

    PubMed

    Mayerhofer, Peter U; Ba-Polo, Manuel; Mingarro, Ismael; Johnson, Arthur E

    2016-02-01

    The long-standing paradigm that all peroxisomal proteins are imported post-translationally into pre-existing peroxisomes has been challenged by the detection of peroxisomal membrane proteins (PMPs) inside the endoplasmic reticulum (ER). In mammals, the mechanisms of ER entry and exit of PMPs are completely unknown. We show that the human PMP PEX3 inserts co-translationally into the mammalian ER via the Sec61 translocon. Photocrosslinking and fluorescence spectroscopy studies demonstrate that the N-terminal transmembrane segment (TMS) of ribosome-bound PEX3 is recognized by the signal recognition particle (SRP). Binding to SRP is a prerequisite for targeting of the PEX3-containing ribosomenascent chain complex (RNC) to the translocon, where an ordered multistep pathway integrates the nascent chain into the membrane adjacent to translocon proteins Sec61? and TRAM. This insertion of PEX3 into the ER is physiologically relevant because PEX3 then exits the ER via budding vesicles in an ATP-dependent process. This study identifies early steps in human peroxisomal biogenesis by demonstrating sequential stages of PMP passage through the mammalian ER. PMID:26572236

  2. ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery.

    PubMed

    Schuck, Sebastian; Gallagher, Ciara M; Walter, Peter

    2014-09-15

    Selective autophagy of damaged or redundant organelles is an important mechanism for maintaining cell homeostasis. We found previously that endoplasmic reticulum (ER) stress in the yeast Saccharomyces cerevisiae causes massive ER expansion and triggers the formation of large ER whorls. Here, we show that stress-induced ER whorls are selectively taken up into the vacuole, the yeast lysosome, by a process termed ER-phagy. Import into the vacuole does not involve autophagosomes but occurs through invagination of the vacuolar membrane, indicating that ER-phagy is topologically equivalent to microautophagy. Even so, ER-phagy requires neither the core autophagy machinery nor several other proteins specifically implicated in microautophagy. Thus, autophagy of ER whorls represents a distinct type of organelle-selective autophagy. Finally, we provide evidence that ER-phagy degrades excess ER membrane, suggesting that it contributes to cell homeostasis by controlling organelle size. PMID:25052096

  3. Visiting the ER: the endoplasmic reticulum as a target for therapeutics in traffic related diseases.

    PubMed

    Aridor, Meir

    2007-08-10

    The endoplasmic reticulum (ER) is a central processor that controls the expression of functional proteins, required for the communication of the cell with the external environment. Plasma membranes receptors, ion channels, secreted hormones, catabolic and metabolic enzymes are folded and assembled in the ER. Key metabolic functions are also regulated from the ER. Molecular quality control monitors ER processing activities and co-ordinates these activities with cell and organism demands. Recent understandings of the molecular basis for ER processing activities illuminate the key role of the ER in the development of a variety of diseases. ER derived diseases include specific genetic disorders such as cystic fibrosis or highly prevalent diseases including diabetes and a range of neurodegenerative diseases. ER processing also plays a key role in the development of cancer. This review summarizes the molecular basis for ER processing functions and current avenues in ER-targeted drug development. PMID:17681635

  4. ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery

    PubMed Central

    Schuck, Sebastian; Gallagher, Ciara M.; Walter, Peter

    2014-01-01

    ABSTRACT Selective autophagy of damaged or redundant organelles is an important mechanism for maintaining cell homeostasis. We found previously that endoplasmic reticulum (ER) stress in the yeast Saccharomyces cerevisiae causes massive ER expansion and triggers the formation of large ER whorls. Here, we show that stress-induced ER whorls are selectively taken up into the vacuole, the yeast lysosome, by a process termed ER-phagy. Import into the vacuole does not involve autophagosomes but occurs through invagination of the vacuolar membrane, indicating that ER-phagy is topologically equivalent to microautophagy. Even so, ER-phagy requires neither the core autophagy machinery nor several other proteins specifically implicated in microautophagy. Thus, autophagy of ER whorls represents a distinct type of organelle-selective autophagy. Finally, we provide evidence that ER-phagy degrades excess ER membrane, suggesting that it contributes to cell homeostasis by controlling organelle size. PMID:25052096

  5. Effects of Y3+/Er3+ ratio on the 2.7 μm emission of Er3+ ions in oxyfluoride glass-ceramics

    NASA Astrophysics Data System (ADS)

    Zhao, Zhiyong; Liu, Chao; Xia, Mengling; Wang, Jing; Han, Jianjun; Xie, Jun; Zhao, Xiujian

    2016-04-01

    Y3+/Er3+ ions co-doped oxyfluoride glass-ceramics were investigated to realize efficient 2.7 μm emission. Incorporation of Er3+ ions into the fluoride nanocrystals was confirmed by the X-ray diffraction patterns, absorption spectra, emission spectra and Judd-Ofelt analysis. With an increase in the Y3+/Er3+ ratio, radiative lifetime, quantum efficiency and emission cross section of the 2.7 μm emission from Er3+ ions were greatly improved, due to the reduced effective concentration of Er3+ ions and suppressed cross relaxation processes among Er3+ ions in the fluoride nanocrystals. Compared to other Er3+-doped glasses, Y3+/Er3+ co-doped oxyfluoride glass-ceramics showed a promising potential for gain medium.

  6. THE CONTRIBUTION OF ER STRESS TO LIVER DISEASES

    PubMed Central

    Dara, Lily; Ji, Cheng; Kaplowitz, Neil

    2011-01-01

    The unfolded protein response (UPR) is an evolutionarily conserved cell signaling pathway which is activated to regulate protein synthesis and restore homeostatic equilibrium when the cell is stressed from increased client protein load or the accumulation of unfolded or malfolded proteins. Once activated, this signaling pathway can either result in the recovery of homeostasis, , or can activate a cascade of events which ultimately result in cell death. The UPR/ER stress response spectrum and its interplay with other cellular organelles play an important role in the pathogenesis of disease in secretory cells rich in endoplasmic reticulum, such as hepatocytes. Over the past two decades the contribution of ER stress to various forms of liver diseases has been examined. Robust support for a contributing as opposed to a secondary role for ER stress response is seen in the nonalcoholic steatohepatitis (NASH), alcoholic liver disease, ischemia reperfusion injury and cholestatic models of liver disease. The exact direction of the cause and effect relationship between modes of cell injury and ER stress remains elusive. It is apparent that a complex interplay exists between ER stress response, conditions that promote it, and those that result from it. A vicious cycle in which ER stress promotes inflammation, cell injury and steatosis and in which steatogenesis, inflammation and cell injury aggravate ER stress seems to be at play. It is perhaps the nature of such a vicious cycle that is the key pathophysiologic concept. Therapeutic approaches aimed at interrupting the cycle may dampen the stress response and the ensuing injury. PMID:21384408

  7. Structural Analysis of the QCM Aboard the ER-2

    NASA Technical Reports Server (NTRS)

    Jones, Phyllis D.; Bainum, Peter M.; Xing, Guangqian

    1997-01-01

    As a result of recent supersonic transport (SST) studies on the effect they may have on the atmosphere, several experiments have been proposed to capture and evaluate samples of the stratosphere where SST's travel. One means to achieve this is to utilize the quartz crystal microbalance (QCM) installed aboard the ER-2, formerly the U-2 reconnaissance aircraft. The QCM is a cascade impactor designed to perform in-situ, real-time measurements of aerosols and chemical vapors at an altitude of 60,000 - 70,000 feet. The ER-2 is primarily used by NASA for Earth resources to test new sensor systems before they are placed aboard satellites. One of the main reasons the ER-2 is used for this flight experiment is its capability to fly approximately twelve miles above sea level (can reach an altitude of 78,000 feet). Because the ER-2 operates at such a high altitude, it is of special interest to scientists interested in space exploration or supersonic aircraft. Some of the experiments are designed to extract data from the atmosphere around the ER-2. For the current flight experiment, the QCM is housed in a frame that is connected to an outer pod that is attached to the fuselage of the ER-2. Due to the location of the QCM within the housing frame and the location of the pod on the ER-2, the pod and its contents are subject to structural loads. In addition to structural loads, structural vibrations are also of importance because the QCM is a frequency induced instrument. Therefore, a structural analysis of the instrument within the frame is imperative to determine if resonance and/or undesirable deformations occur.

  8. 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

  9. The widow(er)'s limit provision of Social Security.

    PubMed

    Weaver, D A

    Widow benefits have been a part of the Social Security program since the 1939 amendments to the Social Security Act (widower benefits were added later). For many years, the Social Security law called for paying a widow(er) a fraction of the deceased worker's primary insurance amount (PIA). However, the worker--while alive--may have received the full PIA as his or her retirement benefit. Over time, arguments were made that a widow(er) should be treated as generously as his or her spouse was. The 1972 amendments to the Social Security Act allowed for a widow(er) to receive a full PIA, subject to actuarial reductions if the widow(er) benefit was claimed before the normal retirement age (NRA) and subject to a new provision of the law commonly referred to as the widow(er)'s limit. Generally, the widow(er)'s limit specifies that if a worker received reduced retirement benefits (because the worker claimed benefits before the NRA), then the worker's widow(er) cannot receive a monthly benefit equal to the full PIA. Rather, the widow(er)'s benefit is generally limited to the amount the worker would receive if he or she was still alive. The limit provision appears to be motivated by the overall intent of the 1972 Congress to pay a benefit to a widow(er) that was comparable with what the worker received. A number of changes to the limit provision have been discussed. This article looks at the following options: Abolishing the limit, Raising the limit by requiring that it never be set below the average PIA among all retired-worker beneficiaries. Adjusting the limit for some widow(er)s--that is, only persons who are widowed before the NRA (the ARLA option), Making a simpler adjustment to the limit by abolishing it for persons who are widowed before age 62 (the SARLA option), and A proposal by Robert J. Myers that would make modest adjustments to the limit for cases in which the worker died before the NRA. The most fundamental change--abolishing the limit--would increase benefits for about 2.8 million widow(er)s and would cost about $3.1 billion a year. Most of the additional government expenditures would not go to the poor and the near poor. Another change would be more successful in aiding low-income widow(er)s: requiring that the limit amount never be set below the average PIA among all retired-worker beneficiaries. About 58 percent of the government expenditures from that option would be received by the poor and the near poor. Overall, 1.2 million widow(er)s would be helped, and the cost would be about $816 million a year. Although the limit provision is consistent with the overall intent of the 1972 Congress, it can have effects that may have been unintended and that some policymakers might consider unusual. Persons who delay receipt of Social Security benefits usually receive higher monthly benefit amounts, but a widow(er) who faces a limit cannot increase his or her monthly benefit through delayed receipt of benefits. Thus, many persons who are widowed before the NRA face strong incentives to claim benefits early. That is somewhat unusual because the actuarial adjustments under Social Security are approximately fair, so there are no cost savings to the Social Security program from "forcing" a widow(er) to claim early benefits as opposed to allowing him or her to delay receipt of benefits in exchange for a higher monthly amount. And many widow(er)s would be better off if they could use the Social Security program to, in effect, save (that is, delay receipt of benefits in exchange for a higher amount later). This article analyzes two other options that would provide widow(er)s with additional filing options under Social Security. The ARLA option would ultimately help about 229,000 widow(er)s, and the cost would be small (about $69 million a year). The SARLA option would help about 117,000 widow(er)s, and the cost would be about $41 million a year. Robert J. Myers, a former Chief Actuary of Social Security, has offered a proposal that would provide relief from the widow(er)'s limit in cases in which the worker dies shortly after retirement. That proposal would help about 115,000 widow(er)s, and the cost would be low (about $57 million a year). PMID:12428513

  10. Er:YAG laser debonding of porcelain veneers

    NASA Astrophysics Data System (ADS)

    Buu, Natalie; Morford, Cynthia; Finzen, Frederick; Sharma, Arun; Rechmann, Peter

    2010-02-01

    The removal of porcelain veneers using Er:YAG lasers has not been previously described in the scientific literature. This study was designed to systematically investigate the efficacy of an Er:YAG laser on veneer debonding without damaging the underlying tooth structure, as well as preserving a new or misplaced veneer. Initially, Fourier Transform Infrared Spectroscopy (FTIR) was used on flat porcelain veneer samples (IPS Empress Esthetic; Ivoclar Vivadent, Amherst, NY) to assess which infrared laser wavelengths are transmitted through the veneer. Additionally, FTIR spectra from a veneer bonding cement (RelyX Veneer Cement A1; 3M ESPE, St. Paul, MN) were obtained. While the veneer material showed no characteristic water absorption bands in the FTIR, the bonding cement has a broad H2O/OH absorption band coinciding with the ER:YAG laser emission wavelength. Consequently Er:YAG laser energy transmission through different veneer thicknesses was measured. The porcelain veneers transmitted 11 - 18 % of the incident Er:YAG laser energy depending on their thicknesses (Er:YAG laser: LiteTouch by Syneron; wavelength 2,940 nm, 10 Hz repetition rate, pulse duration 100 μs at 133 mJ/pulse; straight sapphire tip 1,100 μm diameter; Syneron, Yokneam, Israel). Initial signs of cement ablation occurred at approximately 1.8 - 4.0 J/cm2. This can be achieved by irradiating through the veneer with the fiber tip positioned at a distance of 3-6 mm from the veneer surface, and operating the Er:YAG laser with 133 mJ output energy. All eleven veneers bonded on extracted anterior incisor teeth were easily removed using the Er:YAG laser. The removal occurred without damaging underlying tooth structure as verified by light microscopic investigation (Incident Light Microscope Olympus B 50, Micropublisher RTV 3.3 MP, Image Pro software, Olympus). The debonding mainly occurred at the cement/veneer interface. When the samples were stored in saline solution for 5 days and/or an air-waterspray was used during irradiation, there was a high chance that the veneer would fractured during debonding. However if samples were not stored in water and only air spray was used, 75% of the veneers could be removed without any fracture. The use of an Er:YAG laser can be effective in not only debonding porcelain veneers and preserving tooth structure, but also in maintaining veneer integrity.

  11. Coordination of Endoplasmic Reticulum (ER) Signaling During Maize Seed Development

    SciTech Connect

    Boston, Rebecca S.

    2010-11-20

    Seed storage reserves represent one of the most important sources of renewable fixed carbon and nitrogen found in nature. Seeds are well-adapted for diverting metabolic resources to synthesize storage proteins as well as enzymes and structural proteins needed for their transport and packaging into membrane bound storage protein bodies. Our underlying hypothesis is that the endoplasmic reticulum (ER) stress response provides the critical cellular control of metabolic flux required for optimal accumulation of storage reserves in seeds. This highly conserved response is a cellular mechanism to monitor the protein folding environment of the ER and restore homeostasis in the presence of unfolded or misfolded proteins. In seeds, deposition of storage proteins in protein bodies is a highly specialized process that takes place even in the presence of mutant proteins that no longer fold and package properly. The capacity of the ER to deposit these aberrant proteins in protein bodies during a period that extends several weeks provides an excellent model for deconvoluting the ER stress response of plants. We have focused in this project on the means by which the ER senses and responds to functional perturbations and the underlying intracellular communication that occurs among biosynthetic, trafficking and degradative pathways for proteins during seed development.

  12. ER Ursae Majoris: A dwarf nova with surprises

    NASA Astrophysics Data System (ADS)

    de Miguel, Enrique; Patterson, Joe; Kemp, Jonathan; Stein, William; Roberts, George; Campbell, T.; Hambsch, Franz-J.; Krajci, Tom; Dvorak, Shawn; Koff, Robert A.; Morelle, Etienne; Potter, Michael; Cejudo, David; Brady, Steve; Menzies, Kenneth

    2012-05-01

    ER Ursae Majoris is a relatively bright member of the SU UMa-type dwarf novae that undergoes frequent eruptions of amplitude ~2 mag every ~4 d. In addition to these ordinary dwarf-nova outbursts, ER UMa shows brighter eruptions (superoutbursts) lasting ~20 d with a recurrence time of ~44 d. As other members of the SU UMa class, ER UMa displays a characteristic periodic modulation (superhumps) in its light curve during the course of a superoutburst, the period being a few percent longer than the orbital period of the underlying binary system. A routine photometric patrol of ER UMa during its January 2011superoutburst became much more interesting after noticing the presence of an additional modulation in its light curve, with a period slightly shorter than the orbital period. Similar photometric waves (known as negative superhumps) have already been observed in other cataclysmic variables, mainly in nova-like systems, but only in a small handful of SU UMa-type stars during quiescence, and never before during a superoutburst. We report in this communication the results of a worldwide photometric campaign that was orchestrated right after the discovery of negative superhumps in ER UMa, and provide a thorough analysis of the data obtained from more than 10 stations of the Center of Backyard Astrophysics (CBA) network, which include more than 1000 hours of photometric data over a 4-month baseline on 2011, and a similar (still in progress) dense coverage in 2012.

  13. ER-2: Flying Laboratory for Earth Science Studies

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    The National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC), (Edwards, California, USA) has two Lockheed Martin Corporation (Bethesda, Maryland) Earth Research-2 (ER-2) aircraft that serve as high-altitude and long-range flying laboratories. The ER-2 has been utilized to conduct scientific studies of stratospheric and tropospheric chemistry, land-use mapping, disaster assessment, preliminary testing and calibration and validation of satellite sensors. The ER-2 aircraft provides experimenters with a wide array of payload accommodation areas with suitable environment control with required electrical and mechanical interfaces. Missions may be flown out of DFRC or from remote bases worldwide. The NASA ER-2 is utilized by a variety of customers, including U.S. Government agencies, civilian organizations, universities, and state governments. The combination of the ER-2 s range, endurance, altitude, payload power, payload volume and payload weight capabilities complemented by a trained maintenance and operations team provides an excellent and unique platform system to the science community.

  14. Towards Understanding ER Fluids Using Sals/rheometry

    NASA Astrophysics Data System (ADS)

    Crosby, Bryan J.; McLeish, Tom; Block, Harry

    This paper details work in Cranfield and Leeds Universities of making a stock of transparent ER fluids, which could later be utilised in a new optical electro rheometer (OER) to be assembled at Leeds University. Two basic routes were attempted. One was to use glass microspheres and the other was to use polymer spheres. In order to increase the strength of the ER effect, it was necessary to increase the volume loading while still maintaining sufficient transmission (about 75% over 2 mm). It was found to be possible to increase the ER effect quite substantially in some instances, and in others it was possible to get a near perfect refractive index match. It was not possible to combine both requirements in one fluid such that a high static yield stress was apparent in a transparent ER fluid. However one fluid was made which gave acceptable diffraction losses at high volume fractions, remained in suspension for extended periods and provide about 700 Pa yield stress at 4kV/mm and about 30% volume fraction viz: untreated poly(ethylene vinyl acetate) microspheres in Cereclor/bromonaphthalene/polystyrene solution. The OER being assembled at Leeds University is intended to record small angle light scattering (SALS) profiles, electrical and mechanical properties of ER fluids simultaneously. The OER is based around a DSR 500 machine purchased from Rheometric Scientific with quartz tools coated with transparent indium tin oxide(ITO), which is capable of measuring both steady state (DC) and oscillatory (AC) material parameters.

  15. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    PubMed

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3?mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits. PMID:25359175

  16. Microtensile bond strength analysis of adhesive systems to Er:YAG and Er,Cr:YSGG laser-treated dentin.

    PubMed

    Ramos, Thaysa Monteiro; Ramos-Oliveira, Thayanne Monteiro; Moretto, Simone Gonçalves; de Freitas, Patricia Moreira; Esteves-Oliveira, Marcella; de Paula Eduardo, Carlos

    2014-03-01

    The aim of this in vitro study was to evaluate the effect of different surface treatments (control, diamond bur, erbium-doped yttrium aluminum garnet (Er:YAG) laser, and erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser) on sound dentin surface morphology and on microtensile bond strength (μTBS). Sixteen dentin fragments were randomly divided into four groups (n = 4), and different surface treatments were analyzed by scanning electron microscopy. Ninety-six third molars were randomly divided into eight groups (n = 12) according to type of surface treatment and adhesive system: G1 = Control + Clearfil SE Bond (SE); G2 = Control + Single Bond (SB); G3 = diamond bur (DB) + SE; G4 = DB + SB, G5 = Er:YAG laser (2.94 μm, 60 mJ, 2 Hz, 0.12 W, 19.3 J/cm(2)) + SE; G6 = Er:YAG + SB, G7 = Er,Cr:YSGG laser (2.78 μm, 50 mJ, 30 Hz, 1.5 W, 4.5 J/cm(2)) + SE; and G8 = Er,Cr:YSGG + SB. Composite blocks were bonded to the samples, and after 24-h storage in distilled/deionized water (37 °C), stick-shaped samples were obtained and submitted to μTBS test. Bond strength values (in megapascal) were analyzed by two-way ANOVA and Tukey tests (α = 0.05). G1 (54.69 ± 7.8 MPa) showed the highest mean, which was statistically significantly higher than all the other groups (p < 0.05). For all treatments, SE showed higher bond strength than SB, except only for Er,Cr:YSGG treatment, in which the systems did not differ statistically from each other. Based on the irradiation parameters considered in this study, it can be concluded that Er:YAG and Er,Cr:YSGG irradiation presented lower values than the control group; however, their association with self-etching adhesive does not have a significantly negative effect on sound dentin (μTBS values of >20 MPa). PMID:23354743

  17. Tapentadol-ER for the treatment of diabetic peripheral neuropathy.

    PubMed

    Games, Gina; Hutchison, Amber

    2013-10-01

    With the prevalence of diabetes mellitus (DM) increasing, pathologic complications such as diabetic peripheral neuropathy (DPN) are also becoming more common. Of those diagnosed with DM, 10% to 20% of patients suffer from painful DPN. Until recently, only pregabalin and duloxetine possessed Food and Drug Administration (FDA) approval for this condition. However, FDA recently approved tapentadol-ER [extended release] (Nucynta ER) for painful DPN. Tapentadol-ER is an opioid analgesic commonly used for the treatment of moderate-to-severe chronic pain that contains a unique dual mechanism acting as both a weak mu-opiod receptor agonist and norepinephine-reuptake inhibitor. It is by way of this unique dual mechanism that allows for effective analgesic effects with increased tolerability. This new FDA approval provides an additional therapeutic option to treat DPN in symptomatic patients. PMID:24129223

  18. The Role of ER Bodies in Brassicaceae Resistance under Clinorotation

    NASA Astrophysics Data System (ADS)

    Romanchuk, S. M.; Kordyum, E. L.

    2013-02-01

    Results of the electron-microscopic investigation of root apices of Arabidopsis thaliana 3- and 7-day old seedlings grown in the stationary conditions and under clinorotation are presented. It was shown the similarity in the root apex cell ultrastructure in control and under clinorotation. In the same time there were some differences in the ultrustructure of statocytes and the distal elongation zone under clinorotation. For the first time, the sensitivity of ER-bodies, which are derivative of granular endoplasmic reticulum and contain a ?-glucosidase enzyme, to the influence of simulated microgravity that was demonstrated by increasing quantity and area of ER-bodies per cell section, as well as by higher variability of their shape under clinorotation. A degree of these changes correlated with the duration of clinorotation. On the basis of obtained data, a protective role of ER-bodies in adaptation of plants to microgravity is discussed.

  19. On the accuracy of ERS-1 orbit predictions

    NASA Technical Reports Server (NTRS)

    Koenig, Rolf; Li, H.; Massmann, Franz-Heinrich; Raimondo, J. C.; Rajasenan, C.; Reigber, C.

    1993-01-01

    Since the launch of ERS-1, the D-PAF (German Processing and Archiving Facility) provides regularly orbit predictions for the worldwide SLR (Satellite Laser Ranging) tracking network. The weekly distributed orbital elements are so called tuned IRV's and tuned SAO-elements. The tuning procedure, designed to improve the accuracy of the recovery of the orbit at the stations, is discussed based on numerical results. This shows that tuning of elements is essential for ERS-1 with the currently applied tracking procedures. The orbital elements are updated by daily distributed time bias functions. The generation of the time bias function is explained. Problems and numerical results are presented. The time bias function increases the prediction accuracy considerably. Finally, the quality assessment of ERS-1 orbit predictions is described. The accuracy is compiled for about 250 days since launch. The average accuracy lies in the range of 50-100 ms and has considerably improved.

  20. A Frame Manipulation Algebra for ER Logical Stage Modelling

    NASA Astrophysics Data System (ADS)

    Furtado, Antonio L.; Casanova, Marco A.; Breitman, Karin K.; Barbosa, Simone D. J.

    The ER model is arguably today's most widely accepted basis for the conceptual specification of information systems. A further common practice is to use the Relational Model at an intermediate logical stage, in order to adequately prepare for physical implementation. Although the Relational Model still works well in contexts relying on standard databases, it imposes certain restrictions, not inherent in ER specifications, which make it less suitable in Web environments. This paper proposes frames as an alternative to move from ER specifications to logical stage modelling, and treats frames as an abstract data type equipped with a Frame Manipulation Algebra (FMA). It is argued that frames, with a long tradition in AI applications, are able to accommodate the irregularities of semi-structured data, and that frame-sets generalize relational tables, allowing to drop the strict homogeneity requirement. A prototype logic-programming tool has been developed to experiment with FMA. Examples are included to help describe the use of the operators.

  1. Mitochondrial Dynamics and the ER: The Plant Perspective

    PubMed Central

    Mueller, Stefanie J.; Reski, Ralf

    2015-01-01

    Whereas contact sites between mitochondria and the ER have been in the focus of animal and fungal research for several years, the importance of this organellar interface and the molecular effectors are largely unknown for plants. This work gives an introduction into known evolutionary differences of molecular effectors of mitochondrial dynamics and interactions between animals, fungi, and plants. Using the model plant Physcomitrella patens, we provide microscopic evidence for the existence of mitochondria-ER interactions in plants and their correlation with mitochondrial constriction and fission. We further investigate a previously identified protein of unknown function (MELL1), and show that it modulates the amount of mitochondrial association to the ER, as well as mitochondrial shape and number. PMID:26779478

  2. Computer Simulations of ER Fluids in did Model

    NASA Astrophysics Data System (ADS)

    Yu, K. W.

    Theoretical investigations on electrorheological (ER) fluids are usually concentrated on monodisperse systems. Real ER fluids must be polydisperse in nature, i.e., the suspended particles can have various sizes and/or different dielectric constants. An initial approach for these studies would be the point-dipole (PD) approximation, which is known to err considerably when the particles approach and finally touch due to multipolar interactions. A dipole-induced-dipole (DID) model is shown to be both more accurate than the PD model and easy to use. The DID model is applied to simulate the athermal aggregation of particles in ER fluids and the aggregation time is found to deviate significantly as compared to the PD model. Moreover, the inclusion of DID force further complicates the results because the symmetry between positive and negative contrasts will be broken by the presence of dipole-induced interactions.

  3. Pathogenic Hijacking of ER-Associated Degradation: Is ERAD Flexible?

    PubMed

    Morito, Daisuke; Nagata, Kazuhiro

    2015-08-01

    ER-associated degradation (ERAD) is a protein clearance mechanism by which misfolded, misassembled, or metabolically regulated proteins are specifically dislocated from the ER into the cytosol and degraded by the ubiquitin proteasome system. ERAD very likely evolved to maintain proteostasis and sterol homeostasis in the ER. However, the ironic truth is that membrane-penetrating transportation and protein degradation machineries in ERAD are preferably hijacked by exogenous pathogens such as viruses and toxins for their invasion and evasion from immunological surveillance. In this Review, we provide an overview of our current understanding of the pathogenic hijacking of the host cell ERAD, in which pathogens exploit the complex ERAD machinery in a variety of manners for their own use, suggesting flexibility and plasticity of the molecular machinery of ERAD. PMID:26253026

  4. Update on the NASA ER-2 Doppler radar system (EDOP)

    NASA Technical Reports Server (NTRS)

    Heymsfield, Gerald M.; Dod, Louis R.; Miller, Lee; Craner, Michael; Vandemark, Douglas

    1991-01-01

    An update on the development status of EDOP, a dual-beam Doppler weather radar to be flown on the NASA ER-2 aircraft, is presented. The EDOP system is an X-band Doppler radar with a dual-beam configuration in the ER-2 nose, such that one beam is nadir pointing and the other at an angle of 35 deg forward of the nadir. The dual beams, as used on ELDORA, directed at, e.g., 20 deg fore and aft of the normal to the fuselage, require only a linear rather than L-shaped flight pattern to compute air motions. On the ER-2, EDOP will essentially map out high-resolution time-height sections of reflectivity and vertical hydrometeor velocity from the nadir beam. Flying EDOP with other ground-based and airborne radars will also provide a more complete picture of the overall 3D precipitation and hydrometeor structure of storms.

  5. Ultra-High Spin Spectroscopy In Er Nuclei

    SciTech Connect

    Simpson, J.

    2008-11-11

    The discoveries observed in the ongoing conflict between collective and single-particle nuclear behaviour with increasing angular momentum have driven the field of nuclear spectroscopy for many decades and have given rise to new nuclear phenomena. Recently a new frontier of {gamma} spectroscopy at ultra-high spin has been opened in the rare-earth region with rotational bands that bypass the classic band-terminating states that appear at spin 45({Dirac_h}/2{pi}) in the N 90 Er nuclei. These weakly populated rotational structures have characteristics of triaxial strongly-deformed bands. Such structures have been observed in {sup 157,158,160}Er, following a series of experiments using the Gammasphere spectrometer. These observations herald a return to collective excitations at spins of about 50 to 65({Dirac_h}/2{pi}). This talk reviews the status of the spectroscopy and understanding of the observed structures in these Er and neighbouring nuclei.

  6. Genetic targeting of sprouting angiogenesis using Apln-CreER

    PubMed Central

    Liu, Qiaozhen; Hu, Tianyuan; He, Lingjuan; Huang, Xiuzhen; Tian, Xueying; Zhang, Hui; He, Liang; Pu, Wenjuan; Zhang, Libo; Sun, Heng; Fang, Jing; Yu, Ying; Duan, Shengzhong; Hu, Chaobo; Hui, Lijian; Zhang, Haibin; Quertermous, Thomas; Xu, Qingbo; Red-Horse, Kristy; Wythe, Joshua D.; Zhou, Bin

    2015-01-01

    Under pathophysiological conditions in adults, endothelial cells (ECs) sprout from pre-existing blood vessels to form new ones by a process termed angiogenesis. During embryonic development, Apelin (APLN) is robustly expressed in vascular ECs. In adult mice, however, APLN expression in the vasculature is significantly reduced. Here we show that APLN expression is reactivated in adult ECs after ischaemia insults. In models of both injury ischaemia and tumor angiogenesis, we find that Apln-CreER genetically labels sprouting but not quiescent vasculature. By leveraging this specific activity, we demonstrate that abolishment of the VEGF–VEGFR2 signalling pathway as well as ablation of sprouting ECs diminished tumour vascularization and growth without compromising vascular homeostasis in other organs. Collectively, we show that Apln-CreER distinguishes sprouting vessels from stabilized vessels in multiple pathological settings. The Apln-CreER line described here will greatly aid future mechanistic studies in both vascular developmental biology and adult vascular diseases. PMID:25597280

  7. ?(9)-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor ? (ER?).

    PubMed

    Takeda, Shuso; Yoshida, Kazutaka; Nishimura, Hajime; Harada, Mari; Okajima, Shunsuke; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Watanabe, Kazuhito; Omiecinski, Curtis J; Aramaki, Hironori

    2013-07-15

    ?(9)-Tetrahydrocannabinol (?(9)-THC) has been reported as possessing antiestrogenic activity, although the mechanisms underlying these effects are poorly delineated. In this study, we used the estrogen receptor ? (ER?)-positive human breast cancer cell line, MCF-7, as an experimental model and showed that ?(9)-THC exposures markedly suppresses 17?-estradiol (E2)- induced MCF-7 cell proliferation. We demonstrate that these effects result from ?(9)-THC's ability to inhibit E2-liganded ER? activation. Mechanistically, the data obtained from biochemical analyses revealed that (i) ?(9)-THC up-regulates ER?, a repressor of ER?, inhibiting the expression of E2/ER?-regulated genes that promote cell growth and that (ii) ?(9)-THC induction of ER? modulates E2/ER? signaling in the absence of direct interaction with the E2 ligand binding site. Therefore, the data presented support the concept that ?(9)-THC's antiestrogenic activities are mediated by the ER? disruption of E2/ER? signaling. PMID:23718638

  8. HDLs Protect Pancreatic β-Cells Against ER Stress by Restoring Protein Folding and Trafficking

    PubMed Central

    Pétremand, Jannick; Puyal, Julien; Chatton, Jean-Yves; Duprez, Jessica; Allagnat, Florent; Frias, Miguel; James, Richard W.; Waeber, Gérard; Jonas, Jean-Christophe; Widmann, Christian

    2012-01-01

    Endoplasmic reticulum (ER) homeostasis alteration contributes to pancreatic β-cell dysfunction and death and favors the development of diabetes. In this study, we demonstrate that HDLs protect β-cells against ER stress induced by thapsigargin, cyclopiazonic acid, palmitate, insulin overexpression, and high glucose concentrations. ER stress marker induction and ER morphology disruption mediated by these stimuli were inhibited by HDLs. Using a temperature-sensitive viral glycoprotein folding mutant, we show that HDLs correct impaired protein trafficking and folding induced by thapsigargin and palmitate. The ability of HDLs to protect β-cells against ER stress was inhibited by brefeldin A, an ER to Golgi trafficking blocker. These results indicate that HDLs restore ER homeostasis in response to ER stress, which is required for their ability to promote β-cell survival. This study identifies a cellular mechanism mediating the beneficial effect of HDLs on β-cells against ER stress-inducing factors. PMID:22399686

  9. Luminescent properties of Er and Si co-implanted silicates

    NASA Astrophysics Data System (ADS)

    Pellegrino, P.; Garrido, B.; Lebour, Y.; Moreno, J. A.; Garcia, C.; Morante, J. R.; Bettotti, P.; Pavesi, L.; Prassas, M.

    2005-02-01

    An extensive research for optical active materials at 1540 nm is currently being carried out, on the steam of the strong need for optoelectronic devices which can be integrated with the mainstream Si technology. The formation of silica films doped with Er and Si clusters has been shown as one of the promising approaches. We explored the emission properties of different silicate glasses co-implanted with silicon and Er ions to various doses. As starting materials we used soda-lime and aluminium silicates, glasses which show a larger optical bandwidth than silica at 1540 nm. A Si multi-implantation scheme has been adopted for a planar profile. The best conditions to precipitate Si and activate the Er atoms have been investigated. Optimal annealing temperatures have been found around 500 C, depending on the particular composition of the original glass substrate. The structural analysis of the resulting structures ensures that the best emission properties are the ones for which a phase separation between the implanted Si and the matrix occurs, even without the formation of crystalline aggregates. A comprehensive study of the emission properties is given as a function of the matrix characteristics, Si and Er content, excitation wavelength and power density. It is shown an increase of the emission enhancement of the Er atoms due to the presence of Si cluster when increasing the excitation power. Modelling of the interaction between the absorbing Si nanoprecipitates and the emitting Er atoms has been carried out, in order to estimate the relevant physical parameters which describe the PL process.

  10. Induction of ER Stress in Macrophages of Tuberculosis Granulomas

    PubMed Central

    Seimon, Tracie A.; Kim, Mi-Jeong; Blumenthal, Antje; Koo, Jovanka; Ehrt, Sabine; Wainwright, Helen; Bekker, Linda-Gail; Kaplan, Gilla; Nathan, Carl; Tabas, Ira; Russell, David G.

    2010-01-01

    Background The endoplasmic reticulum (ER) stress pathway known as the Unfolded Protein Response (UPR) is an adaptive survival pathway that protects cells from the buildup of misfolded proteins, but under certain circumstances it can lead to apoptosis. ER stress has been causally associated with macrophage apoptosis in advanced atherosclerosis of mice and humans. Because atherosclerosis shares certain features with tuberculosis (TB) with regard to lesional macrophage accumulation, foam cell formation, and apoptosis, we investigated if the ER stress pathway is activated during TB infection. Principal Findings Here we show that ER stress markers such as C/EBP homologous protein (CHOP; also known as GADD153), phosphorylated inositol-requiring enzyme 1 alpha (Ire1?) and eukaryotic initiation factor 2 alpha (eIF2?), and activating transcription factor 3 (ATF3) are expressed in macrophage-rich areas of granulomas in lungs of mice infected with virulent Mycobacterium tuberculosis (Mtb). These areas were also positive for numerous apoptotic cells as assayed by TUNEL. Microarray analysis of human caseous TB granulomas isolated by laser capture microdissection reveal that 73% of genes involved in the UPR are upregulated at the mRNA transcript level. The expression of two ER stress markers, ATF3 and CHOP, were also increased in macrophages of human TB granulomas when assayed by immunohistochemistry. CHOP has been causally associated with ER stress-induced macrophage apoptosis. We found that apoptosis was more abundant in granulomas as compared to non-granulomatous tissue isolated from patients with pulmonary TB, and apoptosis correlated with CHOP expression in areas surrounding the centralized areas of caseation. Conclusions In summary, ER stress is induced in macrophages of TB granulomas in areas where apoptotic cells accumulate in mice and humans. Although macrophage apoptosis is generally thought to be beneficial in initially protecting the host from Mtb infection, death of infected macrophages in advanced granulomas might favor dissemination of the bacteria. Therefore future work is needed to determine if ER-stress is causative for apoptosis and plays a role in the host response to infection. PMID:20856677

  11. Millijoule pulse energy 100-nanosecond Er-doped fiber laser.

    PubMed

    Kotov, Leonid; Likhachev, Mikhail; Bubnov, Mikhail; Medvedkov, Oleg; Lipatov, Denis; Guryanov, Aleksei; Zaytsev, Kirill; Jossent, Mathieu; Fvrier, Sbastien

    2015-04-01

    We report, for the first time to our knowledge, on a single-mode millijoule-level 100-nanosecond Er-doped fiber laser operating near 1550 nm. The system features a newly developed 35-?m-core Yb-free double-clad Er-doped fiber based on P(2)O(5)-Al(2)O(3)-SiO(2) glass matrix and produces pulses with energy as high as 1 mJ at repetition rates of 1-10 kHz. PMID:25831289

  12. Pilot James Barrilleaux with ER-2 aircraft on ramp

    NASA Technical Reports Server (NTRS)

    1998-01-01

    James Barrilleaux is the assistant chief pilot for ER-2s in the Flight Crew Branch of NASA's Dryden Flight Research Center, Edwards, California. The ER-2s--civilian variants of the military U-2S reconnaissance aircraft--are part of NASA's Airborne Science program. The ER-2s can carry airborne scientific payloads of up to 2,600 pounds to altitudes of about 70,000 feet to investigate such matters as earth resources, celestial phenomena, atmospheric chemistry and dynamics, and oceanic processes. Barrilleaux has held his current position since February 1998. Barrilleaux joined NASA in 1986 as a U-2/ER-2 pilot with NASA's Airborne Science program at Ames Research Center, Moffett Field, California. He flew both the U-2C (until 1989) and the ER-2 on a wide variety of missions both domestic and international. Barrilleaux flew high-altitude operations over Antarctica in which scientific instruments aboard the ER-2 defined the cause of ozone depletion over the continent, known as the ozone hole. He has also flown the ER-2 over the North Pole. Barrilleaux served for 20 years in the U.S. Air Force before he joined NASA. He completed pilot training at Reese Air Force Base, Lubbock, Texas, in 1966. He flew 120 combat missions as a F-4 fighter pilot over Laos and North Vietnam in 1970 and 1971. He joined the U-2 program in 1974, becoming the commander of an overseas U-2 operation in 1982. In 1983, he became commander of the squadron responsible for training all U-2 pilots and SR-71 crews located at Beale Air Force Base, Marysville, California. He retired from the Air Force as a lieutenant colonel in 1986. On active duty, he flew the U-2, F-4 Phantom, the T-38, T-37, and the T-33. His decorations included two Distinguished Flying Crosses, 12 Air Medals, two Meritorious Service Medals, and other Air Force and South Vietnamese awards. Barrilleaux earned a bachelor of science degree in chemical engineering from Texas A&M University, College Station, in 1964 and a master of science degree in systems management from the University of Southern California in 1979. He has accumulated more than 5,800 hours of flying time over a period of 33 years and is currently the oldest active U-2/ER-2 pilot.

  13. High power, diode pumped Er:YAG for dentistry

    NASA Astrophysics Data System (ADS)

    Hagen, C.; Heinrich, A.; Nussbaumer, B.

    2011-03-01

    Pantec Medical Laser presents a diode pumped Er:YAG laser for dental and hard tissue applications. The diode pumped laser is practically maintenance free and ensures reliable operation over several thousand hours. The high repetition rate with up to 15 W average output power, allows treatments otherwise not feasible with low repetition rate, lamp pumped Er:YAG systems. The variable pulse duration of 10 to 200 ?s combined with the good beam quality ensures precise and fast treatment. First results on enamel ablation as well as the power scalability of the technology to 200 mJ and 30 W average power are also shown.

  14. ERS-1 scatterometer measurements over the Southern Ocean

    NASA Technical Reports Server (NTRS)

    Freilich, M. H.

    1994-01-01

    Backscatter cross section measurements from the ERS-1 Active Microwave Instrument (AMI) scatterometer were reprocessed to vector winds using the Freilich-Dunbar model function and a meteorologically aided ambiguity removal scheme. This consistent data set was used to examine the wind field over the Southern Ocean from 20 to 60 deg South. The large number of ERS-1 measurements allows relatively accurate calculation of annual mean wind, stress, and curl fields as well as overall statistics of the winds at mid to high southern latitudes. The long duration of the data time series allows preliminary examination of low frequency (semi annual) wind variability.

  15. Ocean wind field measurement performance of the ERS-1 scatterometer

    NASA Technical Reports Server (NTRS)

    Hans, P.; Schuessler, H.

    1984-01-01

    The Active Microwave Instrumentation (AMI), which will be implemented on the ERS-1, is a 5.3 GHz multipurpose radar for land surface imaging, ocean wave spectrum measurement and wind observations over oceans. The imaging and wave measurements apply Synthetic Aperture Radar (SAR) techniques, while wind field detection is performed by the Scatterometer as part of the AMI. The Scatterometer system design was developed and optimized with the aid of a performance simulator. This paper, aimed at giving an overview, is presented about the: (1) ERS-1 Scatterometer system design; (2) Error budget; and the (3) Overall calibration concept.

  16. Topographic mapping from ERS-1 and SEASAT radar interferometry

    NASA Technical Reports Server (NTRS)

    Zebker, Howard A.; Villasenor, John; Madsen, Soren N.

    1992-01-01

    A radar interferometric technique for topographic mapping of surfaces yields a high resolution, globally consistent approach to generation of digital elevation models. The technique is illustrated with maps generated from SEASAT and European Space Agency Remote Sensing Satellite (ERS-1) data. A SEASAT interferometric image of a forested area which includes some unvegetated lava flows is analyzed. An analysis of errors expected from application of the technique to maps generated from ERS-1 data is presented. An orbital scenario for a global mapping mission is outlined.

  17. Next generation Er:YAG fractional ablative laser

    NASA Astrophysics Data System (ADS)

    Heinrich, A.; Vizhanyo, A.; Krammer, P.; Summer, S.; Gross, S.; Bragagna, T.; Bhler, C.

    2011-03-01

    Pantec Biosolutions AG presents a portable fractional ablative laser system based on a miniaturized diode pumped Er:YAG laser. The system can operate at repetition rates up to 500 Hz and has an incorporated beam deflection unit. It is smaller, lighter and cost efficient compared to systems based on lamp pumped Er:YAG lasers and incorporates a skin layer detection to guarantee precise control of the microporation process. The pulse parameters enable a variety of applications in dermatology and in general medicine, as demonstrated by first results on transdermal drug delivery of FSH (follicle stimulating hormone).

  18. Computational modelling of Er(3+): Garnet laser materials

    NASA Technical Reports Server (NTRS)

    Spangler, Lee H.

    1994-01-01

    The Er(3+) ion has attracted a lot of interest for four reasons: (1) Its (4)I(sub 13/2) yields (4)I(sub 15/2) transition lases in the eyesafe region near 1.5 micron; (2) the (4)I(sub 13/2) transition lases near 2.8 micron, an important wavelength for surgical purposes; (3) it displays surprisingly efficient upconversion with lasing observed at 1.7, 1.2, 0.85, 0.56, 0.55, and 0.47 micron following 1.5 micron pumping; and (4) it has absorption bands at 0.96 and 0.81 micron and thus can be diode pumped. However, properties desirable for upconversion reduce the efficiency of 1.5 and 3 micron laser operation and vice versa. Since all of the processes are influenced by the host via the crystal field induced stark splittings in the Er levels, this project undertook modelling of the host influence on the Er lasinng behavior. While growth and measurement of all ten Er(3+) doped garnets is the surest way of identifying hosts which maximize upconversion (or conversly, 1.5 and 3 micron performance), it is also expensive - costing approximately $10,000/material or approximately $100,000 for the materials computationally investigated here. The calculations were performed using a quantum mechanical point charge model developed by Clyde Morrison at Harry Diamond Laboratories. The programs were used to fit the Er:YAG experimental energy levels so that the crystal field parameters, B(sub nm) could be extracted. From these radial factors, rho (sub n) were determined for Er(3+) in garnets. These, in combination with crystal field components, Anm, available from X-ray data, were used to predict energy levels for Er in the other nine garnet hosts. The levels in Er:YAG were fit with an rms error of 12.2/cm over a 22,000/cm range. Predicted levels for two other garnets for which literature values were available had rms errors of less than 17/cm , showing the calculations to be reliable. Based on resonances between pairs of calculated stark levels, the model predicts GSGG as the best host for 1.5 micron laser operation, GSGG or YSAG as the best host for a 2.8 micron operation, and LuGG as the best host for an upconversion material.

  19. 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.

  20. The Genetic Architecture of the Genome-Wide Transcriptional Response to ER Stress in the Mouse

    PubMed Central

    Chow, Clement Y; Wang, Xu; Riccardi, David; Wolfner, Mariana F.; Clark, Andrew G.

    2015-01-01

    Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding how the ER stress response impacts human disease is to determine how the transcriptional response to ER stress varies among individuals. The genetic diversity of the eight mouse Collaborative Cross (CC) founder strains allowed us to determine how genetic variation impacts the ER stress transcriptional response. We used tunicamycin, a drug commonly used to induce ER stress, to elicit an ER stress response in mouse embryonic fibroblasts (MEFs) derived from the CC founder strains and measured their transcriptional responses. We identified hundreds of genes that differed in response to ER stress across these genetically diverse strains. Strikingly, inflammatory response genes differed most between strains; major canonical ER stress response genes showed relatively invariant responses across strains. To uncover the genetic architecture underlying these strain differences in ER stress response, we measured the transcriptional response to ER stress in MEFs derived from a subset of F1 crosses between the CC founder strains. We found a unique layer of regulatory variation that is only detectable under ER stress conditions. Over 80% of the regulatory variation under ER stress derives from cis-regulatory differences. This is the first study to characterize the genetic variation in ER stress transcriptional response in the laboratory mouse. Our findings indicate that the ER stress transcriptional response is highly variable among strains and arises from genetic variation in individual downstream response genes, rather than major signaling transcription factors. These results have important implications for understanding how genetic variation impacts the ER stress response, an important component of many human diseases. PMID:25651210

  1. ER? splice variant expression in four large cohorts of human breast cancer patient tumors.

    PubMed

    Wimberly, Hallie; Han, Gang; Pinnaduwage, Dushanthi; Murphy, Leigh C; Yang, Xiaohong Rose; Andrulis, Irene L; Sherman, Mark; Figueroa, Jonine; Rimm, David L

    2014-08-01

    Though the role of Estrogen Receptor (ER)? in breast cancer has been studied extensively, there is little consensus about the role of alternative ER isoform ER? in breast cancer biology. ER? has significant sequence homology to ER? but is located on a different chromosome and maintains both overlapping and unique functional attributes. Five variants exist, resulting from alternative splicing of the C-terminal region of ER?. The relevance of ER? variants in breast cancer outcomes and response to therapy is difficult to assess because of conflicting reports in the literature, likely due to variable methods used to assess ER? in patient tumors. Here, we quantitatively assess expression of ER? splice variants on over 2,000 breast cancer patient samples. Antibodies against ER? variants were validated for staining specificity in cell lines by siRNA knockdown of ESR2 and staining reproducibility on formalin-fixed paraffin-embedded tissue by quantitative immunofluorescence (QIF) using AQUA technology. We found antibodies against splice variants ER?1 and ER?5, but not ER?2/cx, which were sensitive, specific, and reproducible. QIF staining of validated antibodies showed both ER?1 and ER?5 QIF scores, which have a normal (bell shaped) distribution on most cohorts assessed, and their expression is significantly associated with each other. Extensive survival analyses show that ER?1 is not a prognostic or predictive biomarker for breast cancer. ER?5 appears to be a context-dependent marker of worse outcome in HER2-positive and triple-negative patients, suggesting an unknown biological function in the absence of ER?. PMID:25007965

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

    PubMed

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-10-15

    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-suppressive 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. PMID:26253462

  3. Pahute Mesa Well Development and Testing Analyses for Wells ER-20-7, ER-20-8 #2, and ER-EC-11, Revision 1

    SciTech Connect

    Greg Ruskauff

    2011-12-01

    This report analyzes the following data collected from ER-20-7, ER-20-8 No.2, and ER-EC-11 during WDT operations: (1) Chemical indicators of well development (Section 2.0); (2) Static hydraulic head (Section 3.0); (3) Radiochemistry and geochemistry (Section 4.0); (4) Drawdown observed at locations distal to the pumping well (Section 5.0); and (5) Drilling water production, flow logs, and temperature logs (Section 6.0). The new data are further considered with respect to existing data as to how they enhance or change interpretations of groundwater flow and transport, and an interim small-scale conceptual model is also developed and compared to Phase I concepts. The purpose of well development is to remove drilling fluids and drilling-associated fines from the formation adjacent to a well so samples reflecting ambient groundwater water quality can be collected, and to restore hydraulic properties near the well bore. Drilling fluids can contaminate environmental samples from the well, resulting in nonrepresentative measurements. Both drilling fluids and preexisting fines in the formation adjacent to the well can impede the flow of water from the formation to the well, creating artifacts in hydraulic response data measured in the well.

  4. Effects of Er:YAG and Er,Cr:YSGG lasers on dentine hypersensitivity. Short-term clinical evaluation.

    PubMed

    Aranha, Ana Cecilia Corra; Eduardo, Carlos de Paula

    2012-07-01

    Dentine hypersensitivity (DH) is a painful condition and is a clinical challenge due to the different treatment strategies available. High-intensity lasers have been studied as a possible option. The aim of this randomized, controlled, double-blind clinical study was to evaluate the effects of Er:YAG and Er,Cr:YSGG lasers on DH. The study group comprised 28 subjects who met the inclusion criteria. A visual analogue scale was used to quantify sensitivity before treatment as baseline, immediately before and immediately after treatment, and 1 week and 1 month after treatment. Teeth were assigned to four groups: group 1 control (no treatment), group 2 Er:YAG laser treatment (2 Hz/32.4 mJ/5.9 J/cm(2)), group 3 Er,Cr:YSGG laser treatment (0.25 W/4.4 J/cm(2)), and group 4 Er,Cr:YSGG laser treatment (0.50 W/ 8.9 J/cm(2)). Data were collected and submitted to statistical analysis for both evaporative (air) and mechanical (probe) stimulation. For both the air and probe stimulation no differences were observed between the pretreatment sensitivities. With the evaporative stimulus, the pain level immediately after treatment was reduced; however, after this the values remained stable. Irradiation with the Er:YAG laser was associated with the lowest level of pain. With the mechanical stimulus, group 4 showed the most pronounced decrease in pain immediately after treatment; however, by the end of the study, pain levels had increased. Groups 1, 2 and 3 showed a reduction in pain that was significantly different from that in group 4 after the 4 weeks of clinical follow up. Based on the results and within the limits of this study, it can be concluded that none of the laser treatments studied was capable of completely eliminating pain, but the Er:YAG and Er,Cr:YSGG lasers are suitable for the treatment of DH. PMID:21912983

  5. Estrogen receptor alpha-36 (ER-?36): A new player in human breast cancer.

    PubMed

    Wang, Zhao-Yi; Yin, Li

    2015-12-15

    Prevailing wisdom is that estrogen receptor (ER)-? mediated genomic estrogen signaling is responsible for estrogen-stimulated cell proliferation and development of ER-positive breast cancer. However, accumulating evidence indicates that another estrogen signaling pathway, non-genomic or rapid estrogen signaling, also plays an important role in mitogenic estrogen signaling. Previously, our laboratory cloned a 36?kDa variant of ER-?, ER-?36, and found that ER-?36 is mainly expressed in the cytoplasm and at the plasma membrane. ER-?36 mediates rapid estrogen signaling and inhibits genomic estrogen signaling. In this review, we review and update the biological function of ER-?36 in ER-positive and -negative breast cancer, breast cancer stem/progenitor cells and tamoxifen resistance, potential interaction and cross-talk of ER-?36 with other ERs and growth factor receptors, and intracellular pathways of ER-?36-mediated rapid estrogen signaling. The potential function and underlying mechanism of ER-? in development of ER-positive breast cancer will also be discussed. PMID:25917453

  6. Estrogen receptor ? exon 3-deleted mouse: The importance of non-ERE pathways in ER? signaling

    PubMed Central

    Maneix, Laure; Antonson, Per; Humire, Patricia; Rochel-Maia, Sabrina; Castaeda, Jessica; Omoto, Yoko; Kim, Hyun-Jin; Warner, Margaret; Gustafsson, Jan-ke

    2015-01-01

    In 1998, an estrogen receptor ? (ER?) knockout (KO) mouse was created by interrupting the gene at the DNA binding domain (DBD) with a neocassette. The mutant females were subfertile and there were abnormalities in the brain, prostate, lung, colon, and immune system. In 2008, another ER? mutant mouse was generated by deleting ER? exon 3 which encodes the first zinc finger in the DBD. The female mice of this strain were unable to ovulate but were otherwise normal. The differences in the phenotypes of the two KO strains, have led to questions about the physiological function of ER?. In the present study, we created an ER? exon 3-deleted mouse (ER?-?ex3) and confirmed that the only observable defect was anovulation. Despite the two in-frame stop codons introduced by splicing between exons 2 and 4, an ER? protein was expressed in nuclei of prostate epithelial cells. Using two different anti-ER? antibodies, we showed that an in-frame ligand binding domain and C terminus were present in the ER?-?ex3 protein. Moreover, with nuclear extracts from ER?-?ex3 prostates, there was an ER?-dependent retardation of migration of activator protein-1 response elements in EMSA. Unlike the original knockout mouse, expression of Ki67, androgen receptor, and Dachshund-1 in prostate epithelium was not altered in the ER?-?ex3 mouse. We conclude that very little of ER? transcriptional activity depends on binding to classical estrogen response elements (EREs). PMID:25848008

  7. Total antioxidant status in plasma of breast cancer patients in relation to ER? expression

    PubMed Central

    Murawa, Dawid; Kaczmarek, Leszek; Po?om, Karol; Litwiniuk, Maria

    2013-01-01

    Aim of the study The aim of this pilot study was to evaluate the plasma total antioxidant capacity (TAS) in breast cancer patients in relation to ER? expression. Material and methods The study group consisted of newly diagnosed consecutive female breast cancer patients (n = 41) and controls (n = 28) randomly selected from women with benign breast disease. TAS was determined with the ABTS reagent. Immunostaining for ER? was performed using polyclonal antibodies. ER?, PgR and HER-2 were measured routinely (immunostaining for ER? and PgR with monoclonal antibodies and EnVision detection system; immunohistochemical method/FISH for HER-2 expression). Results The plasma TAS was significantly decreased in the breast cancer patients in comparison to the controls independently of hormonal and lymph node status. The TAS level was not significantly different between breast cancer subgroups either in relation to the ER? expression (ER?+ vs. ER?) or considering the steroid receptor status (ER?+, ER?+, Pg+ vs. ER?+, ER?, Pg+) even in the selected lymph node negative subgroup. Similarly, HER-2 expression did not significantly affect the TAS concentration. A tendency towards higher TAS level in all ER? negative breast cancer subgroups was observed. Conclusions The results might confirm enhanced consumption of plasma antioxidants in breast cancer patients. The determination of ER? isoforms along with parameters of redox status might enable better understanding of their mutual influence. PMID:24592136

  8. Genetic variants in ER cofactor genes and endometrial cancer risk.

    PubMed

    Li, Yuqing; Low, Hui-Qi; Foo, Jia Nee; Darabi, Hatef; Einarsd?ttir, Kristjana; Humphreys, Keith; Spurdle, Amanda; Easton, Douglas F; Thompson, Deborah J; Dunning, Alison M; Pharoah, Paul D P; Czene, Kamila; Chia, Kee Seng; Hall, Per; Liu, Jianjun

    2012-01-01

    Given that the transcriptional regulatory activity of estrogen receptor (ER) is modulated by its biochemical cofactors, genetic variation within the ER cofactor genes may alter cellular response to estrogen exposure and consequently modify the risk for endometrial cancer. We genotyped 685 tagging SNPs within 60 ER cofactor genes in 564 endometrial cancer cases and 1,510 controls from Sweden, and tested their associations with the risk of endometrial cancer. We investigated the associations of individual SNPs by using a trend test as well as multiple SNPs within a gene or gene complex by using multi-variant association analysis. No significant association was observed for any individual SNPs or genes, but a marginal association of the cumulative genetic variation of the NCOA2 complex as a whole (NCOA2, CARM1, CREBBP, PRMT1 and EP300) with endometrial cancer risk was observed (P(adjusted) = 0.033). However, the association failed to be replicated in an independent European dataset of 1265 cases and 5190 controls (P = 0.71). The results indicate that common genetic variants within ER cofactor genes are unlikely to play a significant role in endometrial cancer risk in European population. PMID:22876322

  9. Progress in Polar Oceans Research Using ERS-1 Data

    NASA Technical Reports Server (NTRS)

    Carsey, F.

    1994-01-01

    Data from ERS-1, especially from the AMI Image Mode, or SAR, have been particularly useful in providing data on ice type and motion and oceanic mesoscale features. These data have been used in studies of ocean and ice circulation, climate processes, convection, and have also proved useful in support of operations in ice covered seas.

  10. Completion report for Well Cluster ER-20-6

    SciTech Connect

    1998-02-01

    The Well Cluster ER-20-6 drilling and completion project was conducted during February, March, and April of 1996 in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS), Nye County, Nevada. This project is part of the DOE`s Underground Test Area (UGTA) subproject at the NTS. The primary UGTA tasks include collecting geological, geophysical, and hydrological data from new and existing wells to define groundwater quality as well as pathways and rates of groundwater migration at the NTS. A program of drilling wells near the sites of selected underground nuclear tests (near-field drilling) was implemented as part of the UGTA subproject to obtain site-specific data on the nature and extent of migration of radionuclides produced by an underground nuclear explosion. The ER-20-6 near-field drilling project was originally planned to be very similar to that recently conducted at Well Cluster ER-20-5, which was designed to obtain data on the existing hydrologic regime near the site of an underground nuclear explosion (IT, 1995; IT, 1996a). However, after further consideration of the goals of the near-field drilling program and the characteristics of the BULLION site, the TWG recommended that the ER-20-6 project be redesigned to accommodate a forced-gradient experiment. This proposed experiment is expected to yield more realistic estimates of transport parameters than can be deduced from sampling and testing natural groundwater flow systems.

  11. OpenER, a Dutch Initiative in Open Educational Resources

    ERIC Educational Resources Information Center

    Schuwer, Robert; Mulder, Fred

    2009-01-01

    Over the period 2006-2008, the Dutch Open Universiteit Nederland conducted an experiment in which Open Educational Resources (OER) were offered in an effort to bridge the gap between informal and formal learning and to establish a new style of entry portal to higher education with no barriers at all. OpenER received considerable attention both in

  12. Dietary Supplements Land Thousands in The ER Each Year

    MedlinePLUS

    ... said he was "not surprised at all" that supplements marketed for weight loss and energy were commonly tied to ER visits in this study. According to Geller, the findings should help zero in on the types of supplements that deserve more scrutiny. But one of the ...

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

    SciTech Connect

    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 rainbow 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.

  14. 184AA3: a xenograft model of ER(+) breast adenocarcinoma.

    PubMed

    Hines, William C; Kuhn, Irene; Thi, Kate; Chu, Berbie; Stanford-Moore, Gaelen; Sampayo, Rocío; Garbe, James C; Stampfer, Martha; Borowsky, Alexander D; Bissell, Mina J

    2016-01-01

    Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER(+)) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER(+) adenocarcinomas that had a high proliferative rate and other features consistent with "luminal B" intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44(High) subpopulation was discovered, yet their tumor forming ability was far less than CD44(Low) cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER(+) cancers. This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development. PMID:26661596

  15. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    SciTech Connect

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki; Ogawa, Atsushi; Suzuki, Shunji

    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. The 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.

  16. Enhanced emission of Er3+ from alternately Er doped Si-rich Al2O3 multilayer film with Si nanocrystals as broadband sensitizers

    NASA Astrophysics Data System (ADS)

    Wang, Xiao; Jiang, Zuimin; Xu, Fei; Ma, Zhongquan; Xu, Run; Yu, Bin; Li, Mingzhu; Zheng, Lingling; Fan, Yongliang; Huang, Jian; Lu, Fang

    2012-01-01

    Alternately Er doped Si-rich Al2O3 (Er:SRA) multilayer film, consisting of alternate Er-Si-codoped Al2O3 (Er:Si:Al2O3) and Si-doped Al2O3 (Si:Al2O3) sublayers, has been synthesized by co-sputtering from separated Er, Si, and Al2O3 targets. The dependence of Er3+ related photoluminescence (PL) properties on annealing temperatures over 700-1100 °C was studied. The maximum intensity of Er3+ PL, about 10 times higher than that of the monolayer film, was obtained from the multilayer film annealed at 950 °C. The enhancement of Er3+ PL intensity is attributed to the energy transfer from the silicon nanocrystals in the Si:Al2O3 sublayers to the neighboring Er3+ ions in the Er:Si:Al2O3 sublayers. The PL intensity exhibits a nonmonotonic temperature dependence: with increasing temperature, the integrated intensity almost remains constant from 14 to 50 K, then reaches maximum at 225 K, and slightly increases again at higher temperatures. Meanwhile, the PL integrated intensity at room temperature is about 30% higher than that at 14 K.

  17. Emergency room (ER) referrals and health insurance in the United States.

    PubMed

    Amini, Reza; Swan, James; Yang, Philip; Ingman, Stanley Rusk; Turner, Keith; Sahaf, Robab

    2015-01-01

    This article aims to determine how various health insurance policies affect the rate of emergency room (ER) referrals in the United States. The secondary data, gathered in National Health Measurement Study (NHMS) in 2008 and 2010, was used. The authors identify the relationships between health insurance and ER referrals by using zero-inflated binomial and zero-inflated Poisson regression. About 17% (2008) and 20% (2010) of the respondents had one or more ER referrals in the 2 years; those who were under coverage of governmental health insurance are more likely to refer ER than uninsured group. The differences in ER referrals that ended with hospital admission across different insurance policies are not significant. Health insurance is a remarkable factor in ER referrals; the coverage of health insurance plans can affect consuming the services provided in ER. Governmental insurance plans can increase ER referrals. PMID:25751585

  18. Synthetic Marijuana Lands Thousands of Young People in the ER, Especially Young Males

    MedlinePLUS

    ... People in the ER, Especially Young Males Synthetic Marijuana Lands Thousands of Young People in the ER, ... on the scene a few years ago, synthetic marijuana (MJ)often called Spice or K2has become ...

  19. GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca(2+)-dependent mitochondrial apoptosis.

    PubMed

    Sano, Renata; Annunziata, Ida; Patterson, Annette; Moshiach, Simon; Gomero, Elida; Opferman, Joseph; Forte, Michael; d'Azzo, Alessandra

    2009-11-13

    Mitochondria-associated ER membranes, or MAMs, define the sites of endoplasmic reticulum/mitochondria juxtaposition that control Ca(2+) flux between these organelles. We found that in a mouse model of the human lysosomal storage disease GM1-gangliosidosis, GM1-ganglioside accumulates in the glycosphingolipid-enriched microdomain (GEM) fractions of MAMs, where it interacts with the phosphorylated form of IP3 receptor-1, influencing the activity of this channel. Ca(2+) depleted from the ER is then taken up by the mitochondria, leading to Ca(2+) overload in this organelle. The latter induces mitochondrial membrane permeabilization (MMP), opening of the permeability transition pore, and activation of the mitochondrial apoptotic pathway. This study identifies the GEMs as the sites of Ca(2+) diffusion between the ER and the mitochondria. We propose a new mechanism of Ca(2+)-mediated apoptotic signaling whereby GM1 accumulation at the GEMs alters Ca(2+) dynamics and acts as a molecular effector of both ER stress-induced and mitochondria-mediated apoptosis of neuronal cells. PMID:19917257

  20. Polybasic Trafficking Signal Mediates Golgi Export, ER Retention or ER Export and Retrieval Based on Membrane-Proximity

    PubMed Central

    Duncan, Roy

    2014-01-01

    Trafficking of integral membrane proteins between the ER and Golgi complex, and protein sorting and trafficking between the TGN and endosomal/lysosomal compartments or plasma membranes, are dependent on cis-acting, linear amino acid sorting signals. Numerous sorting signals of this type have been identified in the cytoplasmic domains of membrane proteins, several of which rely on basic residues. A novel Golgi export signal that relies on a membrane-proximal polybasic motif (PBM) was recently identified in the reptilian reovirus p14 protein, a representative of an unusual group of bitopic fusion-associated small transmembrane (FAST) proteins encoded by fusogenic orthoreoviruses and responsible for cell-cell fusion and syncytium formation. Using immunofluorescence microscopy, cell surface immunofluorescence, and endoglycosidase H assays, we now show the p14 PBM can mediate several distinct trafficking functions depending on its proximity to the transmembrane domain (TMD). When present within 4-residues of the TMD it serves as a Golgi export signal, but when located at the C-terminus of the 68-residue p14 cytoplasmic endodomain it functions as an ER retention signal. The PBM has no effect on protein trafficking when located at an internal position in the cytoplasmic domain. When present in both membrane-proximal and -distal locations, the PBMs promote export to, and efficient retrieval from, the Golgi complex. Interestingly, the conflicting trafficking signals provided by two PBMs induces extensive ER tubulation and segregation of ER components. These studies highlight how a single trafficking signal in a simple transmembrane protein can have remarkably diverse, position-dependent effects on protein trafficking and ER morphogenesis. PMID:24714640

  1. Photoluminescence of Gd2O3:Er based materials for conversion of solar energy

    NASA Astrophysics Data System (ADS)

    Kuznetsova, Yu A.; Zatsepin, A. F.

    2015-11-01

    The spectral and luminescence properties of Er3+ activated Gd2O3 compacted powders have been investigated. There are several excitation channels of Er3+ luminescence: interband transitions, the energy transfer from Gd3+ ions and intracenter excitation. The quantum efficiency of the Er3+ ions luminescence under different excitation was calculated.

  2. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced... annuity component, the parent tier II annuity component is zero. (3) Child. The amount of each...

  3. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., or parent. 228.50 Section 228.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving...

  4. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... parent. 228.50 Section 228.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving...

  5. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., or parent. 228.50 Section 228.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving...

  6. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... parent. 228.50 Section 228.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving...

  7. Glyceollins and dehydroglyceollins isolated from soybean act as SERMs and ER subtype-selective phytoestrogens.

    PubMed

    van de Schans, Milou G M; Vincken, Jean-Paul; de Waard, Pieter; Hamers, Astrid R M; Bovee, Toine F H; Gruppen, Harry

    2016-02-01

    Seven prenylated 6a-hydroxy-pterocapans and five prenylated 6a,11a-pterocarpenes with different kinds of prenylation were purified from an ethanolic extract of fungus-treated soybean sprouts. The activity of these compounds toward both human estrogen receptors (hER? and hER?) was determined in a yeast bioassay and the activity toward hER? was additionally tested in an U2-OS based hER? CALUX bioassay. In the yeast bioassay, compounds with chain prenylation showed in general an agonistic mode of action toward hER?, whereas furan and pyran prenylation led to an antagonistic mode of action. Five of these antagonistic compounds had an agonistic mode of action in the U2-OS based hER? CALUX bioassay, implying that these compounds can act as SERMs. The yeast bioassay also identified 8 ER subtype-selective compounds, with either an antagonistic mode of action or no response toward hER? and an agonistic mode of action toward hER?. The ER subtype-selective compounds were characterized by 6a-hydroxy-pterocarpan or 6a,11a-pterocarpene backbone structure. It is suggested that either the extra D-ring or the increase in length to 12-13.5 of these compounds is responsible for an agonistic mode of action toward hER? and, thereby, inducing ER subtype-selective behavior. PMID:26655113

  8. PREDICTING ER BINDING AFFINITY FOR EDC RANKING AND PRIORITIZATION: A COMPARISON OF THREE MODELS

    EPA Science Inventory

    A comparative analysis of how three COREPA models for ER binding affinity performed when used to predict potential estrogen receptor (ER) ligands is presented. Models I and II were developed based on training sets of 232 and 279 rat ER binding affinity measurements, respectively....

  9. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Relationship as remarried widow(er). 222.24... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er) 222.24 Relationship as remarried widow(er). (a) New eligibility. A claimant will have the...

  10. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Relationship as remarried widow(er). 222.24... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er) 222.24 Relationship as remarried widow(er). (a) New eligibility. A claimant will have the...

  11. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Relationship as remarried widow(er). 222.24... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er) 222.24 Relationship as remarried widow(er). (a) New eligibility. A claimant will have the...

  12. Overexpression of ER? is sufficient to inhibit hypoxia-inducible factor-1 transactivation.

    PubMed

    Park, Choa; Lee, YoungJoo

    2014-07-18

    Estrogen receptor (ER) ? is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ER? suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, we attempted to examine the effect of ER? specific ligand on HIF-1 inhibition in ER? positive PC3 cells and ER? transfected MCF-7 cells. ER? specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ER? specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ER? transfected MCF-7 cells. HIF-1 transcriptional activity repression by ER? was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ER? significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ER?. This result shows that unliganded ER? is sufficient to inhibit HIF-1 in systems of overexpression. PMID:24938129

  13. Lentivirus-Mediated siRNA Targeting ER-? Inhibits Tumorigenesis and Induces Apoptosis in Hepatocarcinoma Cells

    PubMed Central

    Jiang, Ping; Cao, Jun; Bai, Wen-Hui

    2015-01-01

    Background and Objectives. Estrogen receptor-? (ER-?) plays important roles in hepatocarcinogenesis. Recent studies have shown that ER-? could lead to cell cycle progression or inhibition of apoptosis. To better understand the role of ER-?, RNA interference (RNAi) was used to inhibit ER-? expression in the human hepatocellular carcinoma (HCC) cells. Methods. Lentivirus-mediated ER-? small interfering RNA (siRNA) was transfected into HCC cells Hep3B. ER-? expression was monitored by real-time polymerase chain reaction (PCR) and western blot. Cell proliferation, apoptosis, and invasion were examined by methyl thiazol tetrazolium (MTT), flow cytometry (FCM), and invasion assay, respectively. Results. ER-? siRNA efficiently downregulated the expression of ER-? in Hep3B cells at both mRNA and protein levels in a time-dependent manner. ER-? siRNA also inhibited cell proliferation and reduced cell invasion (compared with other groups, P < 0.05, resp.). Furthermore, knockdown of ER-? slowed down the cell population at S phase and increased the rate of apoptosis (P < 0.05, resp.). Conclusion. ER-? knockdown suppressed the growth of HCC cells. Thus, ER-? may play a very important role in carcinogenesis of HCC and its knockdown may offer a new potential gene therapy approach for human liver cancer in the future. PMID:26413526

  14. Estradiol-17?, and its CYP450- and COMT-Derived Metabolites Stimulate Proliferation in Uterine Artery ECs: Role of ER-? vs. ER-?

    PubMed Central

    Jobe, Sheikh O.; Ramadoss, Jayanth; Koch, Jill M.; Jiang, Yizhou; Zheng, Jing; Magness, Ronald R

    2010-01-01

    Estradiol-17? and its metabolites which are sequentially synthesized by cytochrome P450s (CYP450s) and catechol-O-methyltransferase (COMT) to form 2 and 4-Hydroxyestradiol (2-OHE2 and 4-OHE2) and 2- and 4-Methoxestradiol (2-ME2, and 4-ME2) are elevated during pregnancy. We investigated whether CYP450s and COMT are expressed in uterine artery endothelial cells (UAECs) and if E2? and its metabolites modulate cell proliferation via ER-? and/or ER-? and play roles in physiologic uterine angiogenesis during pregnancy. Cultured ovine UAECs from pregnant (P-UAECs) and nonpregnant (NP-UAECs) ewes were treated with 0.1-100 nmol/L of E2?, 2-OHE2, 4-OHE2, 2-ME2, and 4-ME2. ER-? or ER-? specificity was tested using ICI 182,780, ER-?-specific MPP, ER-? specific PHTPP antagonists and their respective agonists ER-?-specific PPT and ER-? specific DPN. Angiogenesis was evaluated using BrdU Proliferation Assay. Utilizing confocal microscopy and Western analyses to determine enzyme location and levels, we observed CYP1A1, CYP1A2, CYP1B1, CYP3A4 and COMT expression in UAECs; however, expressions were similar between NP-UAECs and P-UAECs. E2?, 2-OHE2, 4-OHE2, and 4-ME2 treatments concentration-dependently stimulated proliferation in P-UAECs, but not NP-UAECs; 2-ME2 did not stimulate proliferation in either cell type. Proliferative responses of P-UAECs to E2? were solely mediated by ER-?, whereas responses to E2? metabolites were neither ER-? nor ER-? mediated. We demonstrate an important vascular role for E2?, its CYP450- and COMT-derived metabolites and ER-? in uterine angiogenesis regulation during pregnancy that may be dysfunctional in preeclampsia and other cardiovascular disorders. PMID:20212268

  15. Membrane-bound fatty acid desaturases are inserted co-translationally into the ER and contain different ER retrieval motifs at their carboxy termini.

    PubMed

    McCartney, Andrew W; Dyer, John M; Dhanoa, Preetinder K; Kim, Peter K; Andrews, David W; McNew, James A; Mullen, Robert T

    2004-01-01

    Fatty acid desaturases (FADs) play a prominent role in plant lipid metabolism and are located in various subcellular compartments, including the endoplasmic reticulum (ER). To investigate the biogenesis of ER-localized membrane-bound FADs, we characterized the mechanisms responsible for insertion of Arabidopsis FAD2 and Brassica FAD3 into ER membranes and determined the molecular signals that maintain their ER residency. Using in vitro transcription/translation reactions with ER-derived microsomes, we show that both FAD2 and FAD3 are efficiently integrated into membranes by a co-translational, translocon-mediated pathway. We also demonstrate that while the C-terminus of FAD3 (-KSKIN) contains a functional prototypic dilysine ER retrieval motif, FAD2 contains a novel C-terminal aromatic amino acid-containing sequence (-YNNKL) that is both necessary and sufficient for maintaining localization in the ER. Co-expression of a membrane-bound reporter protein containing the FAD2 C-terminus with a dominant-negative mutant of ADP-ribosylation factor (Arf)1 abolished transient localization of the reporter protein in the Golgi, indicating that the FAD2 peptide signal acts as an ER retrieval motif. Mutational analysis of the FAD2 ER retrieval signal revealed a sequence-specific motif consisting of Phi-X-X-K/R/D/E-Phi-COOH, where -Phi- are large hydrophobic amino acid residues. Interestingly, this aromatic motif was present in a variety of other known and putative ER membrane proteins, including cytochrome P450 and the peroxisomal biogenesis factor Pex10p. Taken together, these data describe the insertion and retrieval mechanisms of FADs and define a new ER localization signal in plants that is responsible for the retrieval of escaped membrane proteins back to the ER. PMID:14690501

  16. Identification of novel estrogen receptor (ER) agonists that have additional and complementary anti-cancer activities via ER-independent mechanism.

    PubMed

    Kim, Taelim; Kim, Hye-In; An, Ji-Young; Lee, Jun; Lee, Na-Rae; Heo, Jinyuk; Kim, Ji-Eun; Yu, Jihyun; Lee, Yong Sup; Inn, Kyung-Soo; Kim, Nam-Jung

    2016-04-01

    In this study, a series of bis(4-hydroxy)benzophenone oxime ether derivatives such as 12c, 12e and 12h were identified as novel estrogen receptor (ER) agonists that have additional and complementary anti-proliferative activities via ER-independent mechanism in cancer cells. These compounds are expected to overcome the therapeutic limitation of existing ER agonists such as estradiol and tamoxifen, which have been known to induce the proliferation of cancer cells. PMID:26905830

  17. A Majority of Low (1-10%) ER Positive Breast Cancers Behave Like Hormone Receptor Negative Tumors

    PubMed Central

    Prabhu, Jyothi S.; Korlimarla, Aruna; Desai, Krisha; Alexander, Annie; Raghavan, Rohini; Anupama, CE; Dendukuri, Nandini; Manjunath, Suraj; Correa, Marjorrie; Raman, N; Kalamdani, Anjali; Prasad, MSN; Gopinath, K.S; Srinath, B.S.; Sridhar, T.S.

    2014-01-01

    Background: The 2010 guidelines by ASCO-CAP have mandated that breast cancer specimens with ?1% positively staining cells by immunohistochemistry should be considered Estrogen Receptor (ER) positive. This has led to a subclass of low-ER positive (1-10%) breast cancers. We have examined the biology and clinical behavior of these low ER staining tumors. Methods: We have developed a probabilistic score of the ER-positivity by quantitative estimation of ER related gene transcripts from FFPE specimens. Immunohistochemistry for ER was done on 240 surgically excised tumors of primary breast cancer. Relative transcript abundance of 3 house-keeping genes and 6 ER related genes were determined by q-RT PCR. A logistic regression model using 3 ER associated genes provided the best probability function, and a cut-off value was derived by ROC analysis. 144 high ER (>10%), 75 ER negative and 21 low-ER (1-10%) tumors were evaluated using the probability score and the disease specific survival was compared. Results: Half of the low-ER positive tumors were assigned to the ER negative group based on the probability score; in contrast 95% of ER negative and 92% of the high ER positive tumors were assigned to the appropriate ER group (p<0.0001). The survival of the low-ER group was intermediate between that of the high ER positive and ER negative groups (p<0.05). Conclusion: Our results suggest that the newly lowered ASCO-CAP criteria for ER positivity, leads to the false categorization of biologically ER negative tumors as ER positive ones. This may have particular relevance to India, where we have a much higher proportion of ER negative tumors in general. PMID:24563670

  18. Efficient visible upconversion luminescence in Er3+ and Er3+/Yb3+ co-doped Y2O3 phosphors obtained by solution combustion reaction

    NASA Astrophysics Data System (ADS)

    Singh, Vijay; Haritha, P.; Venkatramu, V.; Kim, S. H.

    Combustion derived Er3+ -doped Y2O3 and Er3+/Yb3+co-doped Y2O3 powders have been characterized by X-ray diffraction, energy dispersive X-ray analysis, Fourier transform infrared spectroscopy and laser excited spectroscopy. Formation of Y2O3 phosphor was confirmed by X-ray diffraction and energy dispersive X-ray analysis. The vibrational properties of Y2O3 powder was studied by Fourier transform infrared spectroscopy. The luminescence spectra of Er3+ -doped and Er3+/Yb3+ co-doped Y2O3 powders were studied under 379 nm excitation. The strong up-conversion luminescence for Er3+ -doped and Er3+/Yb3+ co-doped Y2O3 powders have been observed under 978 nm laser excitation. The effect of Yb3+ addition on optical and luminescence properties of Er3+:Y2O3 powders were studied. The ratio of red to green intensity has been enhanced when Er3+ -doped Y2O3 is co-doped with Yb3+ ions. The effect of co-doping of Yb3+ ions on the visible luminescence intensity of Er3+ has been studied and the mechanism responsible for the variation in the green and red intensity is discussed.

  19. Efficient visible upconversion luminescence in Er3+ and Er3+/Yb3+ co-doped Y2O3 phosphors obtained by solution combustion reaction.

    PubMed

    Singh, Vijay; Haritha, P; Venkatramu, V; Kim, S H

    2014-05-21

    Combustion derived Er(3+) -doped Y2O3 and Er(3+)/Yb(3+)co-doped Y2O3 powders have been characterized by X-ray diffraction, energy dispersive X-ray analysis, Fourier transform infrared spectroscopy and laser excited spectroscopy. Formation of Y2O3 phosphor was confirmed by X-ray diffraction and energy dispersive X-ray analysis. The vibrational properties of Y2O3 powder was studied by Fourier transform infrared spectroscopy. The luminescence spectra of Er(3+) -doped and Er(3+)/Yb(3+) co-doped Y2O3 powders were studied under 379nm excitation. The strong up-conversion luminescence for Er(3+) -doped and Er(3+)/Yb(3+) co-doped Y2O3 powders have been observed under 978nm laser excitation. The effect of Yb(3+) addition on optical and luminescence properties of Er(3+):Y2O3 powders were studied. The ratio of red to green intensity has been enhanced when Er(3+) -doped Y2O3 is co-doped with Yb(3+) ions. The effect of co-doping of Yb(3+) ions on the visible luminescence intensity of Er(3+) has been studied and the mechanism responsible for the variation in the green and red intensity is discussed. PMID:24682034

  20. Comparative analysis of ER stress response into HIV protease inhibitors: lopinavir but not darunavir induces potent ER stress response via ROS/JNK pathway.

    PubMed

    Taura, Manabu; Kariya, Ryusho; Kudo, Eriko; Goto, Hiroki; Iwawaki, Takao; Amano, Masayuki; Suico, Mary Ann; Kai, Hirofumi; Mitsuya, Hiroaki; Okada, Seiji

    2013-12-01

    HIV protease inhibitor (PI)-induced ER stress has been associated with adverse effects. Although it is a serious clinical problem for HIV/AIDS patients, comparative analyses of ER stress induction by clinically used PIs have rarely been done. Especially, there is no report on the differential ER stress response between lopinavir (LPV) and darunavir (DRV), although these PIs are the most clinically used PIs. We show here that LPV induces the most potent CHOP expression, ER stress marker, among the 9 Food and Drug Administration (FDA)-approved PIs in human peripheral blood mononuclear cells, several human epithelial cells, and mouse embryonic fibroblasts. LPV induced the most potent ROS production and JNK activation in 9 PIs. A comparison among the most clinically used PIs, ritonavir (RTV), LPV, and DRV, revealed that LPV potently and RTV moderately but not DRV induced ER stress via ROS-dependent JNK activation rather than proteasome inhibition. Finally, we analyzed ER stress induction in tissues of mice intraperitoneally injected with RTV, LPV, and DRV. RTV and LPV but not DRV showed ER stress induction in several mice tissues. In conclusion, we first identify LPV as the most potent ER stress inducing PI among 9 FDA-approved PIs in human cells, and although clinical verification is necessary, we show here that DRV has the advantage of less ROS and ER stress induction potential compared with LPV in vitro and in vivo. PMID:23973637

  1. Low Temperature Magnetic Anomalies in Er5Si3

    NASA Astrophysics Data System (ADS)

    Mohapatra, Niharika; Sampathkumaran, E. V.

    2011-07-01

    We present here the results of magnetic measurements on Er5Si3, a compound crystallizing in Mn5Si3 type hexagonal structure. The magnetic susceptibility and isothermal magnetization data reveal that there is a field induced transition near the critical field of 10 kOe below TN. The low field state (ground state) is antiferromagnetic as inferred from the peak in magnetic susceptibility and linear magnetization behavior with field below 10 kOe. It is interesting to note that the paramagnetic Curie temperature is positive with magnitude nearly same as that of TN, suggesting the existence of a strong ferromagnetic component. The saturation magnetization attains a value of 7?B/Er at 1.8 K.

  2. Sea ice lead dynamics from ERS-1 SAR

    NASA Technical Reports Server (NTRS)

    Stern, Harry L.; Rothrock, D. Andrew; Kwok, Ronald

    1994-01-01

    The use of ERS-1 SAR (Synthetic Aperture Radar) images to measure ice lead changes and ice deformation, and thus to determine their relationships and compare them to theory, is reported. ERS-1 SAR data collected at the Alaska (U.S.) SAR facility are processed into low resolution geocoded images which are used as input to the Geophysical Processor System (GPS). The GPS uses cross correlation and edge detection on sequential pairs of images to track a regular 5 km array of grid points. The result for each sequential image pair is a field of ice displacement that contains, on average, more than 200 vectors. The GPS also classifies all the pixels of the images into one of four ice types based on the normalized backscatter coefficients and a seasonal look-up table. This allows all pixels to be labeled as either multiyear ice or as the first year ice and open water that comprise leads.

  3. Preliminary analysis of ERS-1 SAR for forest ecosystem studies

    NASA Technical Reports Server (NTRS)

    Dobson, M. G.; Pierce, Leland; Sarabandi, Kamal; Ulaby, Fawwaz T.; Sharik, Terry

    1992-01-01

    An image obtained by the C-band VV-polarized ERS-1 SAR is examined with respect to potential land applications. A scene obtained near noon on August 15, 1991, along the U.S.-Canadian border near Sault Ste. Marie is calibrated relative to an array of trihedral corner reflectors and active radar calibrators distributed across the swath. Extensive contemporaneous ground observations of forest stands are used to predict the radar backscattering coefficient sigma at the time of the SAR overpass using a first-order vector radiative transfer model. These predictions generally agree with the calibrated ERS-1 data to within 1 dB. It is demonstrated that the dynamic range of sigma is sufficient to perform limited discrimination of various forest and grassland communities even for a single-date observation. Furthermore, retrieval of near-surface soil moisture is feasible for grass-covered soils when plant biomass is less than 1 tonne/ha.

  4. Polarization maintaining linear cavity Er-doped fiber femtosecond laser

    NASA Astrophysics Data System (ADS)

    Jang, Heesuk; Jang, Yoon-Soo; Kim, Seungman; Lee, Keunwoo; Han, Seongheum; Kim, Young-Jin; Kim, Seung-Woo

    2015-10-01

    We present a polarization-maintaining (PM) type of Er-doped fiber linear oscillator designed to produce femtosecond laser pulses with high operational stability. Mode locking is activated using a semiconductor saturable absorber mirror (SESAM) attached to one end of the linear PM oscillator. To avoid heat damage, the SESAM is mounted on a copper-silicon-layered heat sink and connected to the linear oscillator through a fiber buffer dissipating the residual pump power. A long-term stability test is performed to prove that the proposed oscillator design maintains a soliton-mode single-pulse operation without breakdown of mode locking over a week period. With addition of an Er-doped fiber amplifier, the output power is raised to 180 mW with 60 fs pulse duration, from which an octave-spanning supercontinuum is produced.

  5. Tunable eye-safe Er:YAG laser

    NASA Astrophysics Data System (ADS)

    N?mec, M.; ulc, J.; Indra, L.; Fibrich, M.; Jelnkov, H.

    2015-01-01

    Er:YAG crystal was investigated as the gain medium in a diode (1452 nm) pumped tunable laser. The tunability was reached in an eye-safe region by an intracavity birefringent filter. The four tuning bands were obtained peaking at wavelengths 1616, 1632, 1645, and 1656 nm. The broadest continuous tunability was 6 nm wide peaking at 1616 nm. The laser was operating in a pulsed regime (10 ms pulse length, 10 Hz repetition rate). The maximum mean output power was 26.5 mW at 1645 nm. The constructed system demonstrated the tunability of a resonantly diode-pumped Er:YAG laser which could be useful in the development of compact diode-pumped lasers for spectroscopic applications.

  6. Alaska SAR processor implementation of E-ERS-1

    NASA Technical Reports Server (NTRS)

    Cuddy, David; Chen, Ming-Je; Bicknell, Tom

    1992-01-01

    The synthetic aperture radar (SAR) data processing algorithm used by the Alaska SAR Facility (ASF) for the European Space Agency's first Remote-Sensing Satellite (E-ERS-1) SAR data are examined. Preprocessing highlights two features: signal measurement, which includes signal-to-noise ratio, replica measurement, and noise measurement; and Doppler measurement, which includes clutter lock and autofocus. The custom pipeline architecture performs the main processing with controls at the input interface, range correlator, corner-turn memory, azimuth correlator, and multi-look memory. The control software employs a flexible control scheme. The Committee on Earth Observation Satellites (CEOS) format encapsulates the ASF products. System performance for SAR image processing of E-ERS-1 data is reviewed.

  7. Techniques and applications of SAR interferometry for ERS-1

    NASA Technical Reports Server (NTRS)

    Werner, Charles L.; Small, David L.; Rosen, Paul A.; Hensley, Scott; Zebker, Howard A.

    1993-01-01

    The ERS-1 Synthetic Aperture Radar (SAR) demonstrated that it is possible to measure high resolution topography over large areas using interferometry with repeat orbit data sets. Given that the ERS-1 orbit is known with high precision, an automatic system for generation of interferograms is presented. Least squares estimation using ground control points provides an accurate method for determining the precise interferometric baseline. The system parameters which affect the accuracy of the Digital Elevation Models (DEM's) are errors in the interferometric baseline, decorrelation caused by baseline separation, thermal noise, and surface change. An adaptive filter based on the local interferometric coherence was developed to improve phase unwrapping of the interferogram. Final accuracies of the DEM's generated for single scene pairs in Alaska (U.S.) and Bonn (Germany) are on the order of 5 to 10 m.

  8. Atmospheric Ionizing Radiation (AIR) ER-2 Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, Hsiang; Wilson, John W.; Maiden, D. L.

    1998-01-01

    Atmospheric ionizing radiation (AIR) produces chemically active radicals in biological tissues that alter the cell function or result in cell death. The AIR ER-2 flight measurements will enable scientists to study the radiation risk associated with the high-altitude operation of a commercial supersonic transport. The ER-2 radiation measurement flights will follow predetermined, carefully chosen courses to provide an appropriate database matrix which will enable the evaluation of predictive modeling techniques. Explicit scientific results such as dose rate, dose equivalent rate, magnetic cutoff, neutron flux, and air ionization rate associated with those flights are predicted by using the AIR model. Through these flight experiments, we will further increase our knowledge and understanding of the AIR environment and our ability to assess the risk from the associated hazard.

  9. Ho:Tm:Er:LuAG and Two Wavelength Oscillation

    NASA Technical Reports Server (NTRS)

    Barnes, Norman P.; Murray, Keith E.; Walsh, Brian M.; Hutcheson, Ralph L.

    1997-01-01

    Ho:Tm:Er:LuAG demonstrated simultaneous laser oscillation associated with two different transitions and different atoms. Two wavelength oscillation, or TWO, can be achieved in a single laser and single resonator. Moreover, the wavelength can be electronically controlled by varying the pump pulse length, Either the short wavelength, the Ho (5)1(sub 7) to (5)1(sub 8) transition at 2.1 microns, or the long wavelength, the Er (4)1(sub 11/2) to (4)1(sub 13/2) transition at 2.7 microns, or both wavelengths simultaneously can be produced without resorting to mechanical intervention. Consequently, a single laser system can easily switch between producing either of these useful wavelengths. Laser operation of both transitions has been characterized and is presented.

  10. Diode pumped cascade Er:Y2O3 laser

    NASA Astrophysics Data System (ADS)

    Sanamyan, T.

    2015-12-01

    A cascade, diode-pumped, continuous wave (CW), dual-wavelength operation in a 0.5% Er3+:Y2O3 cryogenic ceramic laser is demonstrated for the first time. The laser operates on cascaded Er (4I11/2?????4I13/2?????4I15/2) transitions and can deliver 24 and 13?W at 1.6 and 2.7 ?m, respectively. The overall efficiency with respect to the absorbed ~980?nm power was 62%. This is, to our best knowledge, the first demonstration of an efficient, high power, cascade, erbium laser achieved in bulk solid-state lasers. The analysis of the output power, the lasers wavelengths and slope efficiency for each individual laser transition are presented for pure CW operation mode. Also presented are the temporal behaviors of each laser line as a function of pump pulse duration in the quasi-CW regime.

  11. Er:YAG and adhesion in conservative dentistry : clinical overview

    PubMed Central

    Fornaini, Carlo

    2013-01-01

    The notion of utilizing laser technology in conservative dentistry was proposed in 1990 by Hibst and Keller, who introduced the possibility of using an Er:YAG laser as alternative to conventional instruments such as the turbine and micro-motor. In subsequent years a continuing effort has been made by clinicians, researchers and commercial companies to improve the technology. The aim of this clinical study is to demonstrate, by the description of different clinical cases, the possibilities and the advantages of using Er:YAG lasers in conservative dentistry and to show that better results may be achieved in terms of stronger adhesion, less invasiveness, reduced pain as well as greater comfort and satisfaction of patients. PMID:24155547

  12. Compartmentalization of endoplasmic reticulum quality control and ER-associated degradation factors.

    PubMed

    Leitman, Julia; Ron, Efrat; Ogen-Shtern, Navit; Lederkremer, Gerardo Z

    2013-01-01

    Recent studies are delineating a detailed picture of the architecture and function of the endoplasmic reticulum (ER) and the early secretory pathway, showing the existence of dynamic compartmentalization of ER quality control and ER-associated degradation (ERAD) factors. The compartmentalization is regulated by ER protein load and in turn regulates protein processing and cell fate. This compartmentalization is intimately linked to the protein quality control processes, protein disposal through ERAD, the unfolded protein response, and the initiation of apoptosis. It includes novel compartments, the ER-derived quality control compartment (ERQC), vesicles implicated in "ERAD-tuning," and the mitochondria-associated membranes (MAMs). PMID:23194074

  13. Final Report DE-FG02-07ER64416

    SciTech Connect

    Seymour, Joseph D.

    2014-02-01

    The document provides the Final Report for DE-FG02-07ER64416 on the use of magnetic resonance (MR) methods to quantify transport in porous media impacted by biological and chemical processes. Products resulting from the research in the form of peer reviewed publications and conference presentations are presented. The research correlated numerical simulations and MR measurements to test simulation methodology. Biofilm and uranium detection by MR was demonstrated.

  14. Completion Report for Well Cluster ER-5-4

    SciTech Connect

    U.S. Department of Energy, National Nuclear Security Administration, Nevada Site Office; Bechtel Nevada

    2005-02-01

    Well Cluster ER-5-4 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. The cluster consists of two wells, positioned about 30 meters apart on the same drill pad, constructed as part of a hydrogeologic investigation program for Frenchman Flat at the Nevada Test Site. Detailed lithologic descriptions with preliminary stratigraphic assignments for the well cluster are included in this report. These are based on composite drill cuttings collected every 3 meters, and 156 sidewall samples taken at various depths below 192 meters in both boreholes, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies of rock samples were conducted on 122 samples. Well ER-5-4 penetrated approximately 1,120 meters of Quaternary and Tertiary alluvium before reaching total depth in Tertiary volcanic rocks at 1,137.5 meters. The deeper Well ER-5-4 No.2 penetrated 1,120.4 meters of alluvial sediments, and was terminated within Tertiary volcanic rocks at a depth of 2,133.6 meters, indicating that Paleozoic rocks are deeper than expected at this site.

  15. Capsaicin induces apoptosis in PC12 cells through ER stress

    PubMed Central

    KRIZANOVA, OLGA; STELIAROVA, IVETA; CSADEROVA, LUCIA; PASTOREK, MICHAL; HUDECOVA, SONA

    2014-01-01

    Capsaicin, the pungent agent in chili peppers, has been shown to act as a tumor-suppressor in cancer. In our previous study, capsaicin was shown to induce apoptosis in the rat pheochromocytoma cell line (PC12 cells). Thus, the aim of the present study was to determine the potential mechanism by which capsaicin induces apoptosis. We treated PC12 cells with 50, 100 and 500 ?M capsaicin and measured the reticular calcium content and expression of the reticular calcium transport systems. These results were correlated with endoplasmic reticulum (ER) stress markers CHOP, ATF4 and X-box binding protein 1 (XBP1), as well as with apoptosis induction. We observed that capsaicin decreased reticular calcium in a concentration-dependent manner. Simultaneously, expression levels of the sarco/endoplasmic reticulum pump and ryanodin receptor of type 2 were modified. These changes were accompanied by increased ER stress, as documented by increased stress markers. Thus, from these results we propose that in PC12 cells capsaicin induces apoptosis through increased ER stress. PMID:24337105

  16. Completion report for Well ER-19-1

    SciTech Connect

    1995-12-01

    Well ER-19-1 was drilled for the U.S. Department of Energy (DOE), Nevada Operations Office (DOE/NV), in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS), Nye County, Nevada. IT Corporation (IT) was the principal environmental contractor for the project. The roles and responsibilities of IT and other contractors involved in the project are described in the Raytheon Services Nevada (RSN) Drilling and Completion Programs. The Well ER-19-1 investigation is part of the DOE`s Underground Test Area (UGTA) project at the NTS. The goals of the UGTA project include collecting geological, geophysical, hydrological, and water chemistry data from new and existing wells to define groundwater migration pathways, migration rates, and quality at the NTS. An additional major objective of drilling Well ER-19-1 was to develop dual-wall, reverse-circulation drilling technology for use on small-diameter wells at the NTS. The well will become part of the UGTA monitoring well network.

  17. Capsaicin induces apoptosis in PC12 cells through ER stress.

    PubMed

    Krizanova, Olga; Steliarova, Iveta; Csaderova, Lucia; Pastorek, Michal; Hudecova, Sona

    2014-02-01

    Capsaicin, the pungent agent in chili peppers, has been shown to act as a tumor-suppressor in cancer. In our previous study, capsaicin was shown to induce apoptosis in the rat pheochromocytoma cell line (PC12 cells). Thus, the aim of the present study was to determine the potential mechanism by which capsaicin induces apoptosis. We treated PC12 cells with 50, 100 and 500 M capsaicin and measured the reticular calcium content and expression of the reticular calcium transport systems. These results were correlated with endoplasmic reticulum (ER) stress markers CHOP, ATF4 and X-box binding protein 1 (XBP1), as well as with apoptosis induction. We observed that capsaicin decreased reticular calcium in a concentration-dependent manner. Simultaneously, expression levels of the sarco/endoplasmic reticulum pump and ryanodin receptor of type 2 were modified. These changes were accompanied by increased ER stress, as documented by increased stress markers. Thus, from these results we propose that in PC12 cells capsaicin induces apoptosis through increased ER stress. PMID:24337105

  18. Emerging features of ER resident J-proteins in plants

    PubMed Central

    Ohta, Masaru; Takaiwa, Fumio

    2014-01-01

    J-proteins are co-chaperone components of the HSP70 system. J-proteins stimulate Hsp70ATPase activity, which is responsible for stabilizing the interaction of Hsp70 with client proteins. J-proteins are localized in various intracellular compartments including the cytoplasm, mitochondria and endoplasmic reticulum (ER). Five types of ER resident J-proteins (ERdjs) have been found in plants (P58, ERdj2, ERdj2A, ERdj3B and ERdj7). Rice OsERdj3A is located in the vacuole and protein storage vacuoles (PSV, PB-II) under conditions of ER stress. J-proteins that are localized to the vacuole or lysosome are not found in mammals and yeast, suggesting that the presence of OsERdj3A in the vacuole is plant-specific and one of the features unique to plant ERdjs. In this review, we summarize the current state of knowledge and recent research advancements regarding plant ERdjs, and compare mammalian and yeast ERdjs with plant ERdjs. PMID:24614601

  19. Er-doped LiNbO3 waveguide lasers

    NASA Astrophysics Data System (ADS)

    Sohler, Wolfgang; Suche, Hubertus

    1997-05-01

    The state-of-the-art of Er-doped integrated optical lasers in LiNbO3 is reviewed. They are fabricated in Er- diffusion doped substrates with Ti-diffused channel guides of high quality. The laser resonators are formed by dielectric mirrors vacuum-deposited on the polished waveguide end faces. Five different types of Ti:Er:LiNbO3 waveguide lasers are presented.Among them are free running Fabry-Perot lasers of six different wavelengths in the range 153nm < (lambda) < 1610nm with a cw-output power up to 63mW. They have a shot noise limited relative intensity noise at frequencies above 50MHz. Tunable lasers have been developed by the intracavity integration of an acoustooptical amplifying wavelength filter yielding a tuning range up to 31nm. With an intracavity electrooptic phase modulator modelocked laser operation has been obtained with pulse repetition frequencies up to 10GHz; pulses of only a few ps width could be generated. With an intracavity amplitude modulator Q-switched laser operation has been achieved with up to 2.4W pulse peak power at 2kHz repetition frequency. Moreover, distributed Bragg reflector lasers of emission linewidth < 8kHz have been developed using a dry- etched surface grating as one of the mirrors of the laser cavity.

  20. Completion Report for Well Cluster ER-6-1

    SciTech Connect

    Bechtel Nevada

    2004-10-01

    Well Cluster ER-6-1 was constructed for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Division at the Nevada Test Site, Nye County, Nevada. This work was initiated as part of the Groundwater Characterization Project, now known as the Underground Test Area Project. The well cluster is located in southeastern Yucca Flat. Detailed lithologic descriptions with stratigraphic assignments for Well Cluster ER-6-1 are included in this report. These are based on composite drill cuttings collected every 3 meters and conventional core samples taken below 639 meters, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies of rock samples were conducted on 11 samples to resolve complex interrelationships between several of the Tertiary tuff units. Additionally, paleontological analyses by the U.S. Geological Survey confirmed the stratigraphic assignments below 539 meters within the Paleozoic sedimentary section. All three wells in the Well ER-6-1 cluster were drilled within the Quaternary and Tertiary alluvium section, the Tertiary volcanic section, and into the Paleozoic sedimentary section.

  1. Post examination of copper ER sensors exposed to bentonite

    NASA Astrophysics Data System (ADS)

    Kosec, Tadeja; Kranjc, Andrej; Rosborg, Bo; Legat, Andra

    2015-04-01

    Copper corrosion in saline solutions under oxic conditions is one of concerns for the early periods of disposal of spent nuclear fuel in deep geological repositories. The main aim of the study was to investigate the corrosion behaviour of copper during this oxic period. The corrosion rate of pure copper was measured by means of thin electrical resistance (ER) sensors that were placed in a test package containing an oxic bentonite/saline groundwater environment at room temperature for a period of four years. Additionally, the corrosion rate was monitored by electrochemical impedance spectroscopy (EIS) measurements that were performed on the same ER sensors. By the end of the exposure period the corrosion rate, as estimated by both methods, had dropped to approximately 1.0 ?m/year. The corrosion rate was also estimated by the examination of metallographic cross sections. The post examination tests which were used to determine the type and extent of corrosion products included different spectroscopic techniques (XRD and Raman analysis). It was confirmed that the corrosion rate obtained by means of physical (ER) and electrochemical techniques (EIS) was consistent with that estimated from the metallographic cross section analysis. The corrosion products consisted of cuprous oxide and paratacamite, which was very abundant. From the types of attack it can be concluded that the investigated samples of copper in bentonite underwent uneven general corrosion.

  2. Root canal preparation with Er:YSGG laser

    NASA Astrophysics Data System (ADS)

    Benthin, Hartmut; Ertl, Thomas P.; Onal, B.; Schruender, Stephan; Mueller, Gerhard J.

    1994-12-01

    The high level of efficiency of hard tissue ablation with Er:YAG and Er:YSGG lasers is well known. Of these lasers it is possible only to transmit Er:YSGG laser radiation with OH reduced quartz fibers. Most of the fibers we use in this study were prepared as hemispherical fiber tips. Fifty single rooted teeth were divided into ten groups (n equals 5). After conventional opening of the pulp chamber, root canal preparation was performed in five groups under water only using the laser. In the other five groups preparation with K-files to size 35 was performed before treatment with laser radiation. All teeth were axially separated with direct access to the root canal and examined in SEM investigations. The groups were compared by measuring the areas with patent dentin tubules. Representative areas were examined by TEM. The temperature at the root surface was measured during laser irradiation with thermocouples positioned at several points. The in-vitro study of the effect of the high delivered energy (50 - 100 mJ per pulse) in the root canal showed a good ablation effect. Most of the dentin tubules were opened. The increase in temperature at the root surface was tolerable.

  3. Spectroscopic properties of Er3+-doped fluorotellurite glasses

    NASA Astrophysics Data System (ADS)

    Miguel, A.; Al-Saleh, M.; Azkargorta, J.; Morea, R.; Gonzalo, J.; Arriandiaga, M. A.; Fernandez, J.; Balda, R.

    2013-09-01

    In this work we report the spectroscopic properties of Er3+-doped fluorotellurite glasses in the 46.6TeO2-18.2ZnO-35.2ZnF2 system for different ErF3 concentrations between 0.5 and 3 wt%. Absorption and emission spectra and lifetimes have been measured in the visible and near infrared regions. Judd-Ofelt analysis has been performed to estimate the radiative transition probabilities. The high content of ZnF2 in this glass decreases the covalency degree in rare-earth site and results in a lower value of ?2 if compared with zinc tellurite glasses. The infrared emissions at 1532 nm are broader by nearly 30 nm in these glasses if compared to silica glass. This broad emission together with the high values of the stimulated emission cross-section and lifetime of level 4I13/2 make these glasses attractive for broadband amplifiers. The decays from level 4I13/2 are single exponentials for all concentrations which indicates a fast energy diffusion between Er3+ ions. Similar values for the critical radius and energy transfer microparameter are obtained for the different concentrations, which supports the dipole-dipole transfer hypothesis.

  4. Tunable, diode side-pumped Er: YAG laser

    DOEpatents

    Hamilton, Charles E. (Bellevue, WA); Furu, Laurence H. (Modesto, CA)

    1997-01-01

    A discrete-element Er:YAG laser, side pumped by a 220 Watt peak-power InGaAs diode array, generates >500 mWatts at 2.94 .mu.m, and is tunable over a 6 nm range near about 2.936 .mu.m. The oscillator is a plano-concave resonator consisting of a concave high reflector, a flat output coupler, a Er:YAG crystal and a YAG intracavity etalon, which serves as the tuning element. The cavity length is variable from 3 cm to 4 cm. The oscillator uses total internal reflection in the Er:YAG crystal to allow efficient coupling of the diode emission into the resonating modes of the oscillator. With the tuning element removed, the oscillator produces up to 1.3 Watts of average power at 2.94 .mu.m. The duty factor of the laser is 6.5% and the repetition rate is variable up to 1 kHz. This laser is useful for tuning to an atmospheric transmission window at 2.935 .mu.m (air wavelength). The laser is also useful as a spectroscopic tool because it can access several infrared water vapor transitions, as well as transitions in organic compounds. Other uses include medical applications (e.g., for tissue ablation and uses with fiber optic laser scalpels) and as part of industrial effluent monitoring systems.

  5. Tunable, diode side-pumped Er:YAG laser

    DOEpatents

    Hamilton, C.E.; Furu, L.H.

    1997-04-22

    A discrete-element Er:YAG laser, side pumped by a 220 Watt peak-power InGaAs diode array, generates >500 mWatts at 2.94 {micro}m, and is tunable over a 6 nm range near about 2.936 {micro}m. The oscillator is a plano-concave resonator consisting of a concave high reflector, a flat output coupler, a Er:YAG crystal and a YAG intracavity etalon, which serves as the tuning element. The cavity length is variable from 3 cm to 4 cm. The oscillator uses total internal reflection in the Er:YAG crystal to allow efficient coupling of the diode emission into the resonating modes of the oscillator. With the tuning element removed, the oscillator produces up to 1.3 Watts of average power at 2.94 {micro}m. The duty factor of the laser is 6.5% and the repetition rate is variable up to 1 kHz. This laser is useful for tuning to an atmospheric transmission window at 2.935 {micro}m (air wavelength). The laser is also useful as a spectroscopic tool because it can access several infrared water vapor transitions, as well as transitions in organic compounds. Other uses include medical applications (e.g., for tissue ablation and uses with fiber optic laser scalpels) and as part of industrial effluent monitoring systems. 4 figs.

  6. Completion report for Well Cluster ER-20-5

    SciTech Connect

    1997-03-01

    The Well Cluster ER-20-5 drilling and completion project was conducted for the US Department of Energy, Nevada Operations Office (DOE/NV), in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS) in Nye County, Nevada. Its primary tasks include collecting geological, geophysical, hydrological, and water chemistry data from new and existing wells to define groundwater quality in addition to pathways and rates of groundwater migration. A program of drilling wells near the sites of selected underground nuclear tests (near-field drilling) was implemented to obtain site-specific data about the nature and extent of migration of radionuclides that might have been produced by an underground nuclear explosion. Well Cluster ER-20-5 is the first near-field drilling project initiated at the NTS. This document presents construction data and summarizes the scientific data gathered during the drilling and well-installation phases for all three holes drilled at Well Cluster ER-20-5. Some of this information is preliminary and unprocessed, but was released so that drilling, geotechnical, well design, and completion data could be rapidly disseminated. Additional information about water levels, aquifer testing, and groundwater sampling will be reported after any of this work is performed. Any additional geologic and/or geophysical investigations conducted for this project is described in one or more analysis and interpretation reports. The lithologic and stratigraphic logs, however, are provided in final form.

  7. Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis.

    PubMed

    Supnet, Charlene; Bezprozvanny, Ilya

    2011-09-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and is at present, incurable. The accumulation of toxic amyloid-beta (Aβ) peptide aggregates in AD brain is thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline, an idea that underlies the 'amyloid hypothesis' of AD etiology in both the familal (FAD) and sporadic forms of the disease. Genetic mutations causing FAD also result in the dysregulation of neuronal calcium (Ca(2+)) handling and may contribute to AD pathogenesis, an idea termed the 'calcium hypothesis' of AD. Mutations in presenilin proteins account for the majority of FAD cases. Presenilins function as catalytic subunits of γ-secretase involved in the generation of Aβ peptide. Recently, we discovered that presenilns function as low-conductance, passive ER Ca(2+) leak channels, independent of γ-secretase activity. We further discovered that many FAD mutations in presenilins results in the loss of ER Ca(2+) leak function activity and Ca(2+) overload in the ER. These results provided potential explanation for abnormal Ca(2+) signaling observed in FAD cells with mutations in presenilns. The implications of these findings for understanding AD pathogenesis are discussed in this article. PMID:21663966

  8. Balanced Ero1 activation and inactivation establishes ER redox homeostasis

    PubMed Central

    Kim, Sunghwan; Sideris, Dionisia P.; Sevier, Carolyn S.

    2012-01-01

    The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction and oxidation of regulatory bonds within Ero1p is essential for maintaining the proper redox balance in the ER. In this paper, we show that Pdi1p is the key regulator of Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds. Pdi1p responded to the availability of free thiols and the relative levels of reduced and oxidized glutathione in the ER to control Ero1p activity and ensure that cells generate the minimum number of disulfide bonds needed for efficient oxidative protein folding. PMID:22412017

  9. Ribosome Deficiency Protects Against ER Stress in Saccharomyces cerevisiae

    PubMed Central

    Steffen, Kristan K.; McCormick, Mark A.; Pham, Kim M.; MacKay, Vivian L.; Delaney, Joe R.; Murakami, Christopher J.; Kaeberlein, Matt; Kennedy, Brian K.

    2012-01-01

    In Saccharomyces cerevisiae, 59 of the 78 ribosomal proteins are encoded by duplicated genes that, in most cases, encode identical or very similar protein products. However, different sets of ribosomal protein genes have been identified in screens for various phenotypes, including life span, budding pattern, and drug sensitivities. Due to potential suppressors of growth rate defects among this set of strains in the ORF deletion collection, we regenerated the entire set of haploid ribosomal protein gene deletion strains in a clean genetic background. The new strains were used to create double deletions lacking both paralogs, allowing us to define a set of 14 nonessential ribosomal proteins. Replicative life-span analysis of new strains corresponding to ORF deletion collection strains that likely carried suppressors of growth defects identified 11 new yeast replicative aging genes. Treatment of the collection of ribosomal protein gene deletion strains with tunicamycin revealed a significant correlation between slow growth and resistance to ER stress that was recapitulated by reducing translation of wild-type yeast with cycloheximide. Interestingly, enhanced tunicamycin resistance in ribosomal protein gene deletion mutants was independent of the unfolded protein response transcription factor Hac1. These data support a model in which reduced translation is protective against ER stress by a mechanism distinct from the canonical ER stress response pathway and further add to the diverse yet specific phenotypes associated with ribosomal protein gene deletions. PMID:22377630

  10. Slug contributes to cancer progression by direct regulation of ER? signaling pathway

    PubMed Central

    LI, YOUQIANG; WU, YANYUAN; ABBATIELLO, THOMAS C.; WU, WARREN L.; KIM, JU RI; SARKISSYAN, MARIANNA; SARKISSYAN, SUREN; CHUNG, SEYUNG S.; ELSHIMALI, YAHYA; VADGAMA, JAYDUTT V.

    2015-01-01

    Hormone therapy targeting estrogen receptor ? (ER?) is the most effective treatment for breast cancer. However, this treatment eventually fails as the tumor develops resistance. Although reduced expression of ER-? is a known contributing factor to endocrine resistance, the mechanism of ER-? downregulation in endocrine resistance is still not fully understood. The present study shows that Slug has an inverse relationship with ER? in breast and prostate cancer patient samples. Also the inhibition of Slug blocks mammary stem cell activity in primary mammary epithelial cells. We hypothesize that Slug may be a key transcription factor in the regulation of ER? expression. To understand the Slug-ER? signaling pathway, we employed resistant cell line MCF-TAMR (ER? relatively negative) derived from its parental MCF-7 (ER? positive) cell line and assessed changes in cell phenotype, activity and response to therapy. Conversely, we performed knockdown of Slug in the high-Slug expressing cell line MDA-MB-231 and assessed reversal of the mesenchymal phenotype. Microarray analysis showed that Slug is overexpressed in high grade breast and prostate cancer tissues. Additionally, Slug overexpression leads to drug resistance. Furthermore, we demonstrated that Slug binds directly to ER? promoter E-boxes and represses ER? expression. This resulted in decrease in epithelial-to-mesenchymal transition in cancer cells. These findings demonstrate that Slug, by regulation of ER? expression, contributes to tumor progression and could serve as an important target for cancer therapy. PMID:25652255

  11. ER stress and its functional link to mitochondria: role in cell survival and death.

    PubMed

    Malhotra, Jyoti D; Kaufman, Randal J

    2011-09-01

    The endoplasmic reticulum (ER) is the primary site for synthesis and folding of secreted and membrane-bound proteins. Proteins are translocated into ER lumen in an unfolded state and require protein chaperones and catalysts of protein folding to assist in proper folding. Properly folded proteins traffic from the ER to the Golgi apparatus; misfolded proteins are targeted to degradation. Unfolded protein response (UPR) is a highly regulated intracellular signaling pathway that prevents accumulation of misfolded proteins in the ER lumen. UPR provides an adaptive mechanism by which cells can augment protein folding and processing capacities of the ER. If protein misfolding is not resolved, the UPR triggers apoptotic cascades. 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. Mitochondria and ER form structural and functional networks (mitochondria-associated ER membranes [MAMs]) essential to maintain cellular homeostasis and determine cell fate under various pathophysiological conditions. Regulated Ca(2+) transfer from the ER to the mitochondria is important in maintaining control of prosurvival/prodeath pathways. We discuss the signaling/communication between the ER and mitochondria and focus on the role of the mitochondrial permeability transition pore in these complex processes. PMID:21813400

  12. ER Stress-Induced Clearance of Misfolded GPI-Anchored Proteins via the Secretory Pathway

    PubMed Central

    Satpute-Krishnan, Prasanna; Ajinkya, Monica; Bhat, Savithri; Itakura, Eisuke; Hegde, RamanujanS.; Lippincott-Schwartz, Jennifer

    2014-01-01

    Summary Proteins destined for the cell surface are first assessed in the endoplasmic reticulum (ER) for proper folding before release into the secretory pathway. This ensures that defective proteins are normally prevented from entering the extracellular environment, where they could be disruptive. Here, we report that, when ER folding capacity is saturated during stress, misfolded glycosylphosphatidylinositol-anchored proteins dissociate from resident ER chaperones, engage export receptors, and quantitatively leave the ER via vesicular transport to the Golgi. Clearance from the ER commences within minutes of acute ER stress, before the transcriptional component of the unfolded protein response is activated. These aberrant proteins then access the cell surface transiently before destruction in lysosomes. Inhibiting this stress-induced pathway by depleting the ER-export receptors leads to aggregation of the ER-retained misfolded protein. Thus, this rapid response alleviates the elevated burden of misfolded proteins in the ER at the onset of ER stress, promoting protein homeostasis in the ER. PMID:25083867

  13. Slug contributes to cancer progression by direct regulation of ER? signaling pathway.

    PubMed

    Li, Youqiang; Wu, Yanyuan; Abbatiello, Thomas C; Wu, Warren L; Kim, Ju Ri; Sarkissyan, Marianna; Sarkissyan, Suren; Chung, Seyung S; Elshimali, Yahya; Vadgama, Jaydutt V

    2015-04-01

    Hormone therapy targeting estrogen receptor ? (ER?) is the most effective treatment for breast cancer. However, this treatment eventually fails as the tumor develops resistance. Although reduced expression of ER-? is a known contributing factor to endocrine resistance, the mechanism of ER-? downregulation in endocrine resistance is still not fully understood. The present study shows that Slug has an inverse relationship with ER? in breast and prostate cancer patient samples. Also the inhibition of Slug blocks mammary stem cell activity in primary mammary epithelial cells. We hypothesize that Slug may be a key transcription factor in the regulation of ER? expression. To understand the Slug-ER? signaling pathway, we employed resistant cell line MCF-TAMR (ER? relatively negative) derived from its parental MCF-7 (ER? positive) cell line and assessed changes in cell phenotype, activity and response to therapy. Conversely, we performed knockdown of Slug in the high-Slug expressing cell line MDA-MB-231 and assessed reversal of the mesenchymal phenotype. Microarray analysis showed that Slug is overexpressed in high grade breast and prostate cancer tissues. Additionally, Slug overexpression leads to drug resistance. Furthermore, we demonstrated that Slug binds directly to ER? promoter E-boxes and represses ER? expression. This resulted in decrease in epithelial-to-mesenchymal transition in cancer cells. These findings demonstrate that Slug, by regulation of ER? expression, contributes to tumor progression and could serve as an important target for cancer therapy. PMID:25652255

  14. Downregulation of ER-?36 expression sensitizes HER2 overexpressing breast cancer cells to tamoxifen.

    PubMed

    Yin, Li; Pan, Xiaohua; Zhang, Xin-Tian; Guo, Yu-Ming; Wang, Zhao-Yi; Gong, Yaoqin; Wang, Molin

    2015-01-01

    Tamoxifen provided a successful treatment for ER-positive breast cancer for many years. However, HER2 overexpressing breast cancer cells respond poorly to tamoxifen therapy presumably by pass. The molecular mechanisms underlying development of tamoxifen resistance have not been well established. Recently, we reported that breast cancer cells with high levels of ER-?36, a variant of ER-?, were resistant to tamoxifen and knockdown of ER-?36 expression in tamoxifen resistant cells with the shRNA method restored tamoxifen sensitivity, indicating that gained ER-?36 expression is one of the underlying mechanisms of tamoxifen resistance. Here, we found that tamoxifen induced expression of ER-?36-EGFR/HER2 positive regulatory loops and tamoxifen resistant MCF7 cells (MCF7/TAM) expressed enhanced levels of the loops. Disruption of the ER-?36-EGFR/HER2 positive regulatory loops with the dual tyrosine kinase inhibitor Lapatinib or ER-?36 down-regulator Broussoflavonol B in tamoxifen resistant MCF7 cells restored tamoxifen sensitivity. In addition, we also found both Lapatinib and Broussoflavonol B increased the growth inhibitory activity of tamoxifen in tumorsphere cells derived from MCF7/TAM cells. Our results thus demonstrated that elevated expression of the ER-?36-EGFR/HER2 loops is one of the mechanisms by which ER-positive breast cancer cells escape tamoxifen therapy. Our results thus provided a rational to develop novel therapeutic approaches for tamoxifen resistant patients by targeting the ER-?36-EGFR/HER2 loops. PMID:25973295

  15. Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER? Inhibition

    PubMed Central

    Huang, Pao-Hsuan; Huang, Chih-Yang; Chen, Mei-Chih; Lee, Yueh-Tsung; Yue, Chia-Herng; Wang, Hsin-Yi

    2013-01-01

    The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines of evidence indicate that emodin and aloe-emodin have estrogenic activity as phytoestrogens. However, their effects on estrogen receptor ? (ER?) activation and breast cancer cell growth remain controversial. The goal of this study is to investigate the effects and molecular mechanisms of emodin and aloe-emodin on breast cancer cell proliferation. Our results indicate that both emodin and aloe-emodin are capable of inhibiting breast cancer cell proliferation by downregulating ER? protein levels, thereby suppressing ER? transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ER? and increased ER? ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ER? dissociation and ER? ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ER? degradation. Although emodin might induce cytosolic ER? degradation, it primarily affected nuclear ER? distribution similar to the action of estrogen when protein degradation was blocked. In conclusion, our data demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell proliferation by targeting ER? protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future. PMID:23864887

  16. X-ray and neutron diffraction of Er-hydride films.

    SciTech Connect

    Rodriguez, Mark Andrew

    2004-10-01

    The outline of this report is: (1) structures of hexagonal Er meal, ErH{sub 2} fluorite, and molybdenum; (2) texture issues and processing effects; (3) idea of pole figure integration; and (4) promising neutron diffraction work. Summary of this report are: (1) ErD{sub 2} and ErT{sub 2} film microstructures are strongly effected by processing conditions; (2) both x-ray and neutron diffraction are being pursued to help diagnose structure/property issues regarding ErT{sub 2} films and these correlations to He retention/release; (3) texture issues are great challenges for determination of site occupancy; and (4) work on pole-figure-integration looks to have promise addressing texture issues in ErD{sub 2} and ErT{sub 2} films.

  17. USP14 inhibits ER-associated degradation via interaction with IRE1{alpha}

    SciTech Connect

    Nagai, Atsushi; Kadowaki, Hisae; Maruyama, Takeshi; Takeda, Kohsuke; Nishitoh, Hideki Ichijo, Hidenori

    2009-02-20

    Accumulation of unfolded proteins within the endoplasmic reticulum (ER) lumen induces ER stress. Eukaryotic cells possess the ER quality control systems, the unfolded protein response (UPR), to adapt to ER stress. IRE1{alpha} is one of the ER stress receptors and mediates the UPR. Here, we identified ubiquitin specific protease (USP) 14 as a binding partner of IRE1{alpha}. USP14 interacted with the cytoplasmic region of IRE1{alpha}, and the endogenous interaction between USP14 and IRE1{alpha} was inhibited by ER stress. Overexpression of USP14 inhibited the ER-associated degradation (ERAD) pathway, and USP14 depletion by small interfering RNA effectively activated ERAD. These findings suggest that USP14 is a novel player in the UPR by serving as a physiological inhibitor of ERAD under the non-stressed condition.

  18. ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly.

    PubMed

    Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios

    2016-03-01

    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. PMID:26877082

  19. ER-PM contacts define actomyosin kinetics for proper contractile ring assembly

    PubMed Central

    Zhang, Dan; Bidone, Tamara; Vavylonis, Dimitrios

    2015-01-01

    Summary 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 (S. 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. PMID:26877082

  20. Donor-State-Enabling Er-Related Luminescence in Silicon: Direct Identification and Resonant Excitation

    SciTech Connect

    Izeddin, I.; Klik, M. A. J.; Gregorkiewicz, T.; Vinh, N. Q.; Bresler, M. S.

    2007-08-17

    We conclusively establish a direct link between formation of an Er-related donor gap state and the 1.5 {mu}m emission of Er in Si. The experiment is performed on Si/Si ratio Er nanolayers where a single type of Er optical center dominates. We show that the Er emission can be resonantly induced by direct pumping into the bound exciton state of the identified donor. Using two-color spectroscopy with a free-electron laser we determine the ionization energy of the donor-state-enabling Er excitation as E{sub D}{approx_equal}218 meV. We demonstrate quenching of the Er-related emission upon ionization of the donor.

  1. Analysis of the miRNA-mRNA-lncRNA networks in ER+ and ER- breast cancer cell lines.

    PubMed

    Wu, Qian; Guo, Li; Jiang, Fei; Li, Lei; Li, Zhong; Chen, Feng

    2015-12-01

    Recently, rapid advances in bioinformatics analysis have expanded our understanding of the transcriptome to a genome-wide level. miRNA-mRNA-lncRNA interactions have been shown to play critical regulatory role in cancer biology. In this study, we discussed the use of an integrated systematic approach to explore new facets of the oestrogen receptor (ER)-regulated transcriptome. The identification of RNAs that are related to the expression status of the ER may be useful in clinical therapy and prognosis. We used a network modelling strategy. First, microarray expression profiling of mRNA, lncRNA and miRNA was performed in MCF-7 (ER-positive) and MDA-MB-231 cells (ER- negative). A co-expression network was then built using co-expression relationships of the differentially expressed mRNAs and lncRNAs. Finally, the selected miRNA-mRNA network was added to the network. The key miRNA-mRNA-lncRNA interaction can be inferred from the network. The mRNA and non-coding RNA expression profiles of the cells with different ER phenotypes were distinct. Among the aberrantly expressed miRNAs, the expression levels of miR-19a-3p, miR-19b-3p and miR-130a-3p were much lower in the MCF-7 cells, whereas that of miR-148b-3p was much higher. In a cluster of miR-17-92, the expression levels of six of seven miRNAs were lower in the MCF-7 cells, in addition to miR-20b in the miR-106a-363 cluster. However, the levels of all the miRNAs in the miR-106a-25 cluster were higher in the MCF-7 cells. In the co-expression networking, CD74 and FMNL2 gene which is involved in the immune response and metastasis, respectively, had a stronger correlation with ER. Among the aberrantly expressed lncRNAs, lncRNA-DLEU1 was highly expressed in the MCF-7 cells. A statistical analysis revealed that there was a co-expression relationship between ESR1 and lncRNA-DLEU1. In addition, miR-19a and lncRNA-DLEU1 are both located on the human chromosome 13q. We speculate that miR-19a might be co-expressed with lncRNA-DLEU1 to co-regulate the expression of ESR1, which influences the occurrence and development of breast cancer cells with different levels of ER expression. Our findings reveal that the status of ER is mainly due to the differences in the mRNA and ncRNA profile between the breast cancer cell lines, and highlight the importance of studying the miRNA-mRNA-lncRNA interactions to completely illustrate the intricate transcriptome. PMID:26416600

  2. STIM1 Is a Novel Component of ER-Chlamydia trachomatis Inclusion Membrane Contact Sites

    PubMed Central

    Agaisse, Herv; Derr, Isabelle

    2015-01-01

    Productive developmental cycle of the obligate intracellular bacterial pathogen Chlamydia trachomatis depends on the interaction of the replicative vacuole, named the inclusion, with cellular organelles. We have recently reported the formation of ER-Inclusion membrane contact sites (MCSs), where the endoplasmic reticulum (ER) is in apposition to the inclusion membrane. These platforms contain the C. trachomatis inclusion membrane protein IncD, the mammalian ceramide transfer protein CERT and the ER resident proteins VAPA/B and were proposed to play a role in the non-vesicular trafficking of lipids to the inclusion. Here, we identify STIM1 as a novel component of ER-Inclusion MCSs. STIM1, an ER calcium (Ca2+) sensor that relocate to ER-Plasma Membrane (PM) MCSs upon Ca2+ store depletion, associated with C. trachomatis inclusion. STIM1, but not the general ER markers Rtn3C and Sec61, was enriched at the inclusion membrane. Ultra-structural studies demonstrated that STIM1 localized to ER-Inclusion MCSs. Time-course experiments showed that STIM1, CERT and VAPB co-localized throughout the developmental cycle. By contrast, Orai1, the PM Ca2+ channel that interacts with STIM1 at ER-PM MCSs, did not associate with C. trachomatis inclusion. Upon ER Ca2+ store depletion, a pool of STIM1 relocated to ER-PM MCSs, while the existing ER-Inclusion MCSs remained enriched in STIM1. Finally, we have identified the CAD domain, which mediates STIM1-Orai1 interaction, as the minimal domain required for STIM1 enrichment at ER-Inclusion MCSs. Altogether this study identifies STIM1 as a novel component of ER-C. trachomatis inclusion MCSs. We discuss the potential role(s) of STIM1 during the infection process. PMID:25915399

  3. Scandium effect on the luminescence of Er-Sc silicates prepared from multi-nanolayer films

    NASA Astrophysics Data System (ADS)

    Najar, Adel; Omi, Hiroo; Tawara, Takehiko

    2014-07-01

    Polycrystalline Er-Sc silicates (Er x Sc2- x Si2O7 and Er x Sc2- x SiO5) were fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on SiO2/Si substrates by RF sputtering and thermal annealing at high temperature. The films were characterized by synchrotron radiation grazing incidence X-ray diffraction, cross-sectional transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate phase Er x Sc2- x Si2O7 is the dominant film, and Er and Sc are homogeneously distributed after thermal treatment because of the excess of oxygen from SiO2 interlayers. The Er concentration of 6.7 1021 atoms/cm3 was achieved due to the presence of Sc that dilutes the Er concentration and generates concentration quenching. During silicate formation, the erbium diffusion coefficient in the silicate phase is estimated to be 1 10-15 cm2/s at 1,250C. The dominant Er x Sc2 - x Si2O7 layer shows a room-temperature photoluminescence peak at 1,537 nm with the full width at half maximum (FWHM) of 1.6 nm. The peak emission shift compared to that of the Y-Er silicate (where Y and Er have almost the same ionic radii) and the narrow FWHM are due to the small ionic radii of Sc3+ which enhance the crystal field strength affecting the optical properties of Er3+ ions located at the well-defined lattice sites of the Sc silicate. The Er-Sc silicate with narrow FWHM opens a promising way to prepare photonic crystal light-emitting devices.

  4. Scandium effect on the luminescence of Er-Sc silicates prepared from multi-nanolayer films

    PubMed Central

    2014-01-01

    Polycrystalline Er-Sc silicates (Er x Sc2-x Si2O7 and Er x Sc2-x SiO5) were fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on SiO2/Si substrates by RF sputtering and thermal annealing at high temperature. The films were characterized by synchrotron radiation grazing incidence X-ray diffraction, cross-sectional transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate phase Er x Sc2-x Si2O7 is the dominant film, and Er and Sc are homogeneously distributed after thermal treatment because of the excess of oxygen from SiO2 interlayers. The Er concentration of 6.7??1021 atoms/cm3 was achieved due to the presence of Sc that dilutes the Er concentration and generates concentration quenching. During silicate formation, the erbium diffusion coefficient in the silicate phase is estimated to be 1??10-15 cm2/s at 1,250C. The dominant Er x Sc2 - x Si2O7 layer shows a room-temperature photoluminescence peak at 1,537 nm with the full width at half maximum (FWHM) of 1.6 nm. The peak emission shift compared to that of the Y-Er silicate (where Y and Er have almost the same ionic radii) and the narrow FWHM are due to the small ionic radii of Sc3+ which enhance the crystal field strength affecting the optical properties of Er3+ ions located at the well-defined lattice sites of the Sc silicate. The Er-Sc silicate with narrow FWHM opens a promising way to prepare photonic crystal light-emitting devices. PMID:25114648

  5. Demineralization of Er:YAG and Er,Cr:YSGG laser-prepared enamel cavities in vitro.

    PubMed

    Apel, C; Schfer, C; Gutknecht, N

    2003-01-01

    The aim of the present study was to establish whether cavity preparation by means of an erbium laser with efficient water cooling is capable of reducing the susceptibility of the prepared dental enamel to demineralization and thus of achieving a potential caries-protective effect in the region of cavity margins. To this end, cavities limited to the enamel were prepared in the crowns of 10 teeth each using an Er:YAG (lambda = 2,940 nm) and an Er,Cr:YSGG laser (lambda = 2,780 nm). A control cavity prepared conventionally with a diamond drill in the same occlusal zone was assigned to each of these cavities. The specimens were then subjected to a pH-cycling caries model. Analysis was performed by quantitatively measuring the demineralization front under a polarized-light microscope. The results of the study showed that enamel cavities prepared with the erbium lasers used display a statistically significant acceleration of demineralization compared to conventionally prepared cavities (p < 0.01). The Er:YAG laser cavities revealed demineralization to a depth of 133.9 (SD 25.7) microm, while the value observed with the Er,Cr:YSGG laser was 133.8 (SD 25.8) microm. The depth of demineralization in the control groups was only 77.4 (SD 13.8) microm and 79.3 (SD 37.6) microm. No difference could be found between the two lasers (p = 0.98). Based on these in vitro tests, it cannot be assumed that use of the erbium laser for cavity preparation offers any advantages in terms of resistance to secondary caries in clinical practice. PMID:12566637

  6. COMPLETION REPORT FOR WELL CLUSTER ER-5-3

    SciTech Connect

    BECHTEL NEVADA

    2005-12-01

    Well Cluster ER-5-3 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This cluster of 3 wells was drilled in 2000 and 2001 as part of a hydrogeologic investigation program in Frenchman Flat. The first borehole in the cluster, Well ER-5-3, was drilled in February and March 2000. A 47.0-centimeter surface hole was drilled and cased off to the depth of 374.8 meters. The hole diameter was decreased to 31.1 centimeters for drilling to a total depth of 794.3 meters within welded ash-flow tuff. A piezometer string with 1 slotted interval was installed in the annulus of the surface casing, open to the saturated alluvium. A completion string with 2 slotted intervals was installed in the main hole, open to saturated alluvium and to the welded tuff aquifer. A second piezometer string with 1 slotted interval open to the welded-tuff aquifer was installed outside the completion string. Well ER-5-3 No.2 was drilled about 30 meters west of the first borehole in March 2000, and was recompleted in March 2001. A 66.0-centimeter hole was drilled and cased off to the depth of 613.8 meters. The hole diameter was decreased to 44.5 centimeters and the borehole was drilled and cased off to the depth of 849.0 meters. The hole diameter was decreased once more to 31.1 centimeters for drilling to a total depth of 1,732.2 meters in dolomite. A completion string open to the dolomite (lower carbonate aquifer) was installed. Well ER-5-3 No.3 was drilled approximately 30 meters north of the first 2 boreholes in February 2001. A 66.0-centimeter hole was drilled and cased off to the depth of 36.6 meters, then the main 25.1-centimeter-diameter hole was drilled to a total depth of 548.6 meters in alluvium. A slotted stainless-steel tubing string was installed in the saturated alluvium. A preliminary composite, static water level was measured at the depth of 282.6 meters, prior to development and hydrologic testing. Detailed lithologic descriptions and stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters, and 120 sidewall samples taken at various depths below 91 meters in Wells ER-5-3 and ER-5-3 No.2, supplemented by geophysical log data. The wells penetrated Quaternary/Tertiary alluvium to the depth of 622.4 meters, and an 8.5-meter-thick basalt flow was encountered within the alluvium. Tertiary tuff was penetrated to the depth of approximately 1,425.9 meters, where the top of the lower carbonate aquifer was tagged in Well ER-5-3 No.2.

  7. Magnetic properties and transformation of crystal structure in the ErFe2-ErAl2 system

    NASA Astrophysics Data System (ADS)

    ?wik, J.; Koshkid'ko, Y.; Mikhailova, A.; Kolchugina, N.; Nenkov, K.; Hackamer, A.; Miller, M.

    2015-03-01

    The modification of structural properties and magnetic behaviour of the ErFe2-xAlx Laves phase intermetallic compounds have been studied while changing the Al content in the range 0.36 ? x ? 1.5. Powder X-ray diffraction study at room temperature showed the formation of the cubic C15 structure, in the samples with Al content of 0.36 ? x < 0.75 and 1.4 ? x ? 2.0. For the intermediate compositions with 0.75 ? x ? 1.4, the hexagonal C14 structure is observed. Magnetic and magnetocaloric properties of polycrystalline ErFe2-xAlx intermetallic compounds were investigated experimentally using magnetic and heat capacity measurements. The Curie temperature TC decreases from 275 to 28 K as the Al content increases from x = 0.36 to x = 1.5, respectively. Magnetization measurements in strong magnetic fields showed the complex mechanism of magnetic saturation in the studied compounds. Under an external field change from 0 to 2 T, the maximum entropy change is 6 J/kg K at T = 28 K for the composition with x = 1.5. The minimum in the concentration dependence of the magnetic entropy change is observed in the vicinity of x equal to 1.25. Regularities of variations of magnetocaloric properties of ErFe2-xAlx intermetallic compounds with increasing Al content are discussed from the point of view of their both structural and magnetic states.

  8. Effects of Er:YAG and Er,Cr:YSGG laser irradiation on the adhesion to eroded dentin.

    PubMed

    Ramos, Thaysa Monteiro; Ramos-Oliveira, Thayanne Monteiro; de Freitas, Patricia Moreira; Azambuja, Nilton; Esteves-Oliveira, Marcella; Gutknecht, Norbert; de Paula Eduardo, Carlos

    2015-01-01

    Limited information is available regarding the adhesion to eroded dentin. This study aims to evaluate the effect of different surface treatments on eroded dentin morphology and on microtensile bond strength (?TBS) of adhesive systems to this substrate. Ninety-six extracted third molars were randomly divided into eight groups (n?=?12) according to the type of surface treatment and the adhesive system: G1?=?Control?+?Clearfil SE Bond [SE], G2?=?Diamond bur [DB]?+?SE, G3?=?Er:YAG laser (60 mJ, 2 Hz, 0.12 W, 19.3 J/?cm(2))?+?SE, G4?=?Er,Cr:YSGG laser (50 mJ, 30 Hz, 1.5 W, 4.5 J/?cm(2))?+?SE, G5?=?Control?+?Single Bond [SB], G6?=?DB?+?SB, G7?=?Er:YAG?+?SB, G8?=?Er,Cr:YSGG?+?SB. The erosive cycling was performed by immersion in 0.05 M citric acid (pH 2.3, 10 min, 6x/day) and in supersaturated solution (pH 7.0, 1 h, between acid attacks), during 5 days. Blocks of composite were bonded to the samples according to the manufacturers' instructions. After 24 h-storage in distilled/deionized water (37 C), stick-shaped samples were obtained and submitted to ?TBS test. Each surface treatment was analyzed under scanning electron microscopy (n?=?4) and the bond strength values (megapascal) were analyzed by two-way ANOVA and Tukey tests (??=?0.05). All surface treatments lead to changes on eroded dentin. G4 showed the highest bond strength mean (28.3??9.2 MPa), which was statistically significant higher than all the other groups (p?Er,Cr:YSGG laser irradiation (4.5 J/cm(2)/50 mJ/30 Hz/140 ?s) prior to bonding with a self-etching adhesive system significantly increases adhesion to eroded dentin, as compared to conventional treatment. PMID:23649611

  9. BODIPY-Coumarin Conjugate as an Endoplasmic Reticulum Membrane Fluidity Sensor and Its Application to ER Stress Models.

    PubMed

    Lee, Hoyeon; Yang, Zhigang; Wi, Youngjin; Kim, Tae Woo; Verwilst, Peter; Lee, Yun Hak; Han, Ga-In; Kang, Chulhun; Kim, Jong Seung

    2015-12-16

    An endoplasmic reticulum (ER) membrane-selective chemosensor composed of BODIPY and coumarin moieties and a long alkyl chain (n-C18) was synthesized. The emission ratio of BODIPY to coumarin depends on the solution viscosity. The probe is localized to the ER membrane and was applied to reveal the reduced ER membrane fluidity under ER stress conditions. PMID:26588433

  10. 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

  11. When supply does not meet demand-ER stress and plant programmed cell death

    PubMed Central

    Williams, Brett; Verchot, Jeanmarie; Dickman, Martin B.

    2014-01-01

    The endoplasmic reticulum (ER) is the central organelle in the eukaryotic secretory pathway. The ER functions in protein synthesis and maturation and is crucial for proper maintenance of cellular homeostasis and adaptation to adverse environments. Acting as a cellular sentinel, the ER is exquisitely sensitive to changing environments principally via the ER quality control machinery. When perturbed, ER-stress triggers a tightly regulated and highly conserved, signal transduction pathway known as the unfolded protein response (UPR) that prevents the dangerous accumulation of unfolded/misfolded proteins. In situations where excessive UPR activity surpasses threshold levels, cells deteriorate and eventually trigger programmed cell death (PCD) as a way for the organism to cope with dysfunctional or toxic signals. The programmed cell death that results from excessive ER stress in mammalian systems contributes to several important diseases including hypoxia, neurodegeneration, and diabetes. Importantly, hallmark features and markers of cell death that are associated with ER stress in mammals are also found in plants. In particular, there is a common, conserved set of chaperones that modulate ER cell death signaling. Here we review the elements of plant cell death responses to ER stress and note that an increasing number of plant-pathogen interactions are being identified in which the host ER is targeted by plant pathogens to establish compatibility. PMID:24926295

  12. Loss of Clcc1 Results in ER Stress, Misfolded Protein Accumulation, and Neurodegeneration

    PubMed Central

    Jia, Yichang; Jucius, Thomas J.; Cook, Susan A.

    2015-01-01

    Folding of transmembrane and secretory proteins occurs in the lumen of the endoplasmic reticulum (ER) before transportation to the cell surface and is monitored by the unfolded protein response (UPR) signaling pathway. The accumulation of unfolded proteins in the ER activates the UPR that restores ER homeostasis by regulating gene expression that leads to an increase in the protein-folding capacity of the ER and a decrease in the ER protein-folding load. However, prolonged UPR activity has been associated with cell death in multiple pathological conditions, including neurodegeneration. Here, we report a spontaneous recessive mouse mutation that causes progressive cerebellar granule cell death and peripheral motor axon degeneration. By positional cloning, we identify the mutation in this strain as a retrotransposon insertion in the Clcc1 gene, which encodes a putative chloride channel localized to the ER. Furthermore, we demonstrate that the C3H/HeSnJ inbred strain has late onset cerebellar degeneration due to this mutation. Interestingly, acute knockdown of Clcc1 expression in cultured cells increases sensitivity to ER stress. In agreement, GRP78, the major HSP70 family chaperone in the ER, is upregulated in Clcc1-deficient granule cells in vivo, and ubiquitinated proteins accumulate in these neurons before their degeneration. These data suggest that disruption of chloride homeostasis in the ER disrupts the protein-folding capacity of the ER, leading to eventual neuron death. PMID:25698737

  13. When supply does not meet demand-ER stress and plant programmed cell death.

    PubMed

    Williams, Brett; Verchot, Jeanmarie; Dickman, Martin B

    2014-01-01

    The endoplasmic reticulum (ER) is the central organelle in the eukaryotic secretory pathway. The ER functions in protein synthesis and maturation and is crucial for proper maintenance of cellular homeostasis and adaptation to adverse environments. Acting as a cellular sentinel, the ER is exquisitely sensitive to changing environments principally via the ER quality control machinery. When perturbed, ER-stress triggers a tightly regulated and highly conserved, signal transduction pathway known as the unfolded protein response (UPR) that prevents the dangerous accumulation of unfolded/misfolded proteins. In situations where excessive UPR activity surpasses threshold levels, cells deteriorate and eventually trigger programmed cell death (PCD) as a way for the organism to cope with dysfunctional or toxic signals. The programmed cell death that results from excessive ER stress in mammalian systems contributes to several important diseases including hypoxia, neurodegeneration, and diabetes. Importantly, hallmark features and markers of cell death that are associated with ER stress in mammals are also found in plants. In particular, there is a common, conserved set of chaperones that modulate ER cell death signaling. Here we review the elements of plant cell death responses to ER stress and note that an increasing number of plant-pathogen interactions are being identified in which the host ER is targeted by plant pathogens to establish compatibility. PMID:24926295

  14. The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria

    PubMed Central

    Marini, E S; Giampietri, C; Petrungaro, S; Conti, S; Filippini, A; Scorrano, L; Ziparo, E

    2015-01-01

    Components of the death receptor-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIPL), a well-known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca2+-release as well as ER-mitochondria tethering was decreased in c-FLIP?/? mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIPL and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIPL emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4. PMID:25501600

  15. The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria.

    PubMed

    Marini, E S; Giampietri, C; Petrungaro, S; Conti, S; Filippini, A; Scorrano, L; Ziparo, E

    2015-07-01

    Components of the death receptor-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIP(L)), a well-known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca(2+)-release as well as ER-mitochondria tethering was decreased in c-FLIP(-/-) mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIP(L) and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIP(L) emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4. PMID:25501600

  16. A conserved endoplasmic reticulum membrane protein complex (EMC) facilitates phospholipid transfer from the ER to mitochondria.

    PubMed

    Lahiri, Sujoy; Chao, Jesse T; Tavassoli, Shabnam; Wong, Andrew K O; Choudhary, Vineet; Young, Barry P; Loewen, Christopher J R; Prinz, William A

    2014-10-01

    Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (ER) to mitochondria. Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in S. cerevisiae to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER membrane protein complex (EMC) has decreased phosphatidylserine (PS) transfer from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE). Cells lacking EMC proteins and the ER-mitochondria tethering complex called ERMES (the ER-mitochondria encounter structure) are inviable, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ER-mitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM) complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth. PMID:25313861

  17. A Conserved Endoplasmic Reticulum Membrane Protein Complex (EMC) Facilitates Phospholipid Transfer from the ER to Mitochondria

    PubMed Central

    Tavassoli, Shabnam; Wong, Andrew K. O.; Choudhary, Vineet; Young, Barry P.; Loewen, Christopher J. R.; Prinz, William A.

    2014-01-01

    Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (ER) to mitochondria. Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in S. cerevisiae to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER membrane protein complex (EMC) has decreased phosphatidylserine (PS) transfer from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE). Cells lacking EMC proteins and the ERmitochondria tethering complex called ERMES (the ERmitochondria encounter structure) are inviable, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ERmitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM) complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth. PMID:25313861

  18. 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; Gunel, 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; Drk, 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, Brge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menndez, Primitiva; Mller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomki, 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; Dieudonn, 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; Labrche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylks, 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; Gonzlez-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; Mller-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, Franoise; 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

    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. PMID:23535733

  19. SERCaMP: a carboxy-terminal protein modification that enables monitoring of ER calcium homeostasis

    PubMed Central

    Henderson, Mark J.; Wires, Emily S.; Trychta, Kathleen A.; Richie, Christopher T.; Harvey, Brandon K.

    2014-01-01

    Endoplasmic reticulum (ER) calcium homeostasis is disrupted in diverse pathologies, including neurodegeneration, cardiovascular diseases, and diabetes. Temporally defining calcium dysregulation during disease progression, however, has been challenging. Here we describe secreted ER calcium-monitoring proteins (SERCaMPs), which allow for longitudinal monitoring of ER calcium homeostasis. We identified a carboxy-terminal modification that is sufficient to confer release of a protein specifically in response to ER calcium depletion. A Gaussia luciferase (GLuc)–based SERCaMP provides a simple and sensitive method to monitor ER calcium homeostasis in vitro or in vivo by analyzing culture medium or blood. GLuc-SERCaMPs revealed ER calcium depletion in rat primary neurons exposed to various ER stressors. In vivo, ER calcium disruption in rat liver was monitored over several days by repeated sampling of blood. Our results suggest that SERCaMPs will have broad applications for the long-term monitoring of ER calcium homeostasis and the development of therapeutic approaches to counteract ER calcium dysregulation. PMID:25031430

  20. 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

  1. SERCaMP: a carboxy-terminal protein modification that enables monitoring of ER calcium homeostasis.

    PubMed

    Henderson, Mark J; Wires, Emily S; Trychta, Kathleen A; Richie, Christopher T; Harvey, Brandon K

    2014-09-15

    Endoplasmic reticulum (ER) calcium homeostasis is disrupted in diverse pathologies, including neurodegeneration, cardiovascular diseases, and diabetes. Temporally defining calcium dysregulation during disease progression, however, has been challenging. Here we describe secreted ER calcium-monitoring proteins (SERCaMPs), which allow for longitudinal monitoring of ER calcium homeostasis. We identified a carboxy-terminal modification that is sufficient to confer release of a protein specifically in response to ER calcium depletion. A Gaussia luciferase (GLuc)-based SERCaMP provides a simple and sensitive method to monitor ER calcium homeostasis in vitro or in vivo by analyzing culture medium or blood. GLuc-SERCaMPs revealed ER calcium depletion in rat primary neurons exposed to various ER stressors. In vivo, ER calcium disruption in rat liver was monitored over several days by repeated sampling of blood. Our results suggest that SERCaMPs will have broad applications for the long-term monitoring of ER calcium homeostasis and the development of therapeutic approaches to counteract ER calcium dysregulation. PMID:25031430

  2. (Arg)3 within the N-terminal domain of glucosidase I contains ER targeting information but is not required absolutely for ER localization.

    PubMed

    Hardt, Birgit; Kalz-Fuller, Burga; Aparicio, Raquel; Volker, Christof; Bause, Ernst

    2003-03-01

    Glucosidase I is an endoplasmic reticulum (ER) type II membrane enzyme that cleaves the distal alpha1,2-glucose of the asparagine-linked GlcNAc2-Man9-Glc3 precursor. To identify sequence motifs responsible for ER localization, we prepared a protein chimera by transferring the cytosolic and transmembrane domain of glucosidase I to the luminal domain of Golgi-Man9-mannosidase. The GIM9 hybrid was overexpressed in COS 1 cells as an ER-resident protein that displayed alpha1,2-mannosidase activity, excluding the possibility that the glucosidase I-specific domains interfere with folding of the Man9-mannosidase catalytic domain. After substitution of the Args in position 7, 8, or 9 relative to the N-terminus by leucine, the GIM9 mutants were transported to the cell surface indicating that the (Arg)3 sequence functions as an ER-targeting motif. Cell surface expression was also observed after substitution of Arg-7 or Arg-8 but not Arg-9 in GIM9 by either lysine or histidine. Thus the side chain structure, including its positive charge, appears to be essential for signal function. Analysis of the N-linked glycans suggests that the (Arg)3 sequence mediates ER localization through Golgi-to-ER retrograde transport. Glucosidase I remained localized in the ER after truncation or mutation of the N-terminal (Arg)3 signal, in contrast to comparable GIM9 mutants. ER localization was also observed with an M9GI chimera consisting of the cytosolic and transmembrane domain of Man9-mannosidase and the glucosidase I catalytic domain. ER-specific targeting information must therefore be provided by sequence motifs contained within the glucosidase I luminal domain. This structural information appears to direct ER localization by retention rather than by retrieval, as concluded from N-linked Man9-GlcNAc2 being the major glycan released from the wild-type enzyme. PMID:12626409

  3. Divergent Regulation of ER and Kiss Genes by 17?-Estradiol in Hypothalamic ARC Versus AVPV Models.

    PubMed

    Treen, Alice K; Luo, Vicky; Chalmers, Jennifer A; Dalvi, Prasad S; Tran, Dean; Ye, Wenqing; Kim, Ginah L; Friedman, Zoey; Belsham, Denise D

    2016-02-01

    Kisspeptin (Kiss) and G-protein-coupled receptor (Gpr)54 have emerged as key regulators of reproduction. 17?-estradiol (E2)-mediated regulation of these neurons is nuclei specific, where anteroventral periventricular (AVPV) Kiss neurons are positively regulated by E2, whereas arcuate nucleus (ARC) neurons are inhibited. We have generated immortalized Kiss cell lines from male and female adult-derived murine hypothalamic primary culture, as well as cell lines from microdissected AVPV and ARC from female Kiss-green fluorescent protein (GFP) mice. All exhibit endogenous Kiss-1 expression, estrogen receptors (ER)s (ER?, ER?, and Gpr30), as well as known markers of AVPV Kiss neurons in the mHypoA-50 and mHypoA-Kiss/GFP-4, vs markers of ARC Kiss neurons in the mHypoA-55 and the mHypoA-Kiss/GFP-3 lines. There was an increase in Kiss-1 mRNA expression at 24 hours in the AVPV lines and a repression of Kiss-1 mRNA at 4 hours in the ARC lines. An E2-mediated decrease in ER? mRNA expression at 24 hours in the AVPV cell lines was detected, and a significant decrease in Gpr30, ER?, and ER? mRNA levels at 4 hours in the ARC cell lines was evident. ER agonists and antagonists determined the specific ERs responsible for mediating changes in gene expression. In the AVPV, ER? is required but not ER? or GPR30, vs the ARC Kiss-expressing cell lines that require GPR30, and either ER? and/or ER?. We determined cAMP response element-binding protein 1 was necessary for the down-regulation of Kiss-1 mRNA expression using small interfering RNA knockdown in the ARC cell model. These studies elucidate some of the molecular events involved in the differential E2-mediated regulation of unique and specific Kiss neuronal models. PMID:26726951

  4. Study of negative and positive superhumps in ER Ursae Majoris

    NASA Astrophysics Data System (ADS)

    Ohshima, Tomohito; Kato, Taichi; Pavlenko, Elena; Akazawa, Hidehiko; Imamura, Kazuyoshi; Tanabe, Kenji; de Miguel, Enrique; Stein, William; Itoh, Hiroshi; Hambsch, Franz-Josef; Dubovsky, Pavol A.; Kudzej, Igor; Krajci, Thomas; Baklanov, Alex; Samsonov, Denis; Antonyuk, Oksana I.; Malanushenko, Viktor; Andreev, Maksim V.; Noguchi, Ryo; Ogura, Kazuyuki; Nomoto, Takashi; Ono, Rikako; Nakagawa, Shin'ichi; Taniuchi, Keisuke; Aoki, Tomoya; Kawabata, Miho; Kimura, Hitoshi; Masumoto, Kazunari; Kobayashi, Hiroshi; Matsumoto, Katsura; Shiokawa, Kazuhiko; Shugarov, Sergey Yu.; Katysheva, Natalia; Voloshina, Irina; Zemko, Polina; Kasai, Kiyoshi; Ruiz, Javier; Maehara, Hiroyuki; Virnina, Natalia; Virtanen, Jani; Miller, Ian; Boitnott, Boyd; Littlefield, Colin; James, Nick; Tordai, Tamas; Robert, Fidrich; Padovan, Stefano; Miyashita, Atsushi

    2014-07-01

    We carried out photometric observations of the SU UMa-type dwarf nova ER UMa during 2011 and 2012, which showed the existence of persistent negative superhumps even during the superoutburst. We performed a two-dimensional period analysis of its light curves by using a method called "least absolute shrinkage and selection operator" (Lasso) and the "phase dispersion minimization" (PDM) analysis, and found that the period of negative superhumps systematically changed between a superoutburst and the next superoutburst. The trend of the period change can be interpreted as a reflection of the change of the disk radius. This change is in agreement with the one predicted by the thermal tidal instability model. The normal outburst during a supercycle showed a general trend that the rising rate to its maximum becomes slower as the next superoutburst is approaching. The change can be interpreted as the consequence of the increased gas-stream flow into the inner region of the disk as a result of the tilted disk. Some of superoutbursts were found to be triggered by a precursor normal outburst when the positive superhump appeared to develop. The positive and negative superhumps coexisted during the superoutburst. Positive superhumps were prominent only for four or five days after the supermaximum, while the signal of negative superhumps became stronger after the middle phase of the superoutburst plateau. A simple combination of the positive and negative superhumps was found to be insufficient for reproduction of the complex profile variation. We were able to detect the developing phase of positive superhumps (stage A superhumps) for the first time in ER UMa-type dwarf novae. Using the period of stage A superhumps, we obtained a mass ratio of 0.100(15), which indicates that ER UMa is on the ordinary evolutional track of cataclysmic variable stars.

  5. Final Report on Grant DE-FG-02ER63350

    SciTech Connect

    John H. Miller

    2005-06-10

    Research funded by grant DE-FG-02ER63350 focused on DNA bending measured NMR spectroscopy and modeled by classical molecular dynamics (MD) simulation. Bending is a structural aspect of DNA that is plays a key role in its function. The most important finding of our research was that oxidation of guanine, a ubiquitous DNA lesion caused by endogenous and environmental oxidative stress, changes DNA bending dynamics in a way that favors binding of glycosylases, repair enzymes that remove damaged bases from DNA. Hence, the effect of 8-oxoguanine on DNA bending contributes to its recognition and removal by the base excision repair system.

  6. Assessing the function of mitochondria-associated ER membranes.

    PubMed

    Area-Gomez, Estela

    2014-01-01

    Mitochondria-associated membranes or MAMs are specific regions within the endoplasmic reticulum in close apposition to mitochondria. These contacts between both organelles are involved in the regulation of several cellular functions such as the import of phosphatidylserine into mitochondria from the ER for decarboxylation to phosphatidylethanolamine, cholesterol esterification, calcium signaling, mitochondrial shape and motility, autophagy, and apoptosis. Recently, MAM alterations have been described to underlie some neurodegenerative diseases, including Alzheimer's disease. In this chapter, we describe and discuss some of the methods to isolate and assay this interesting cellular region. PMID:25416359

  7. ERS-1 radar altimeter: Performance, calibration and data validation

    NASA Astrophysics Data System (ADS)

    Francis, C. R.

    1986-08-01

    Key characteristics of the ERS-1 radar altimeter and of the overall measurement system are described. Operating modes include ocean and ice. Calibration is based on ground test and simulation data and onboard, independent measures. Performance will be established once the hardware implementation is complete. The altimeter is not sensitive to yaw, but a roll tilt mode used when calibrating the wind scatterometer leads to loss of altimeter data. Science data are tape recorded and telemetered in a high speed dump in real time to ground stations.

  8. Completion report for well ER-3-2

    SciTech Connect

    1995-12-01

    Well ER-3-2 was drilled for the U.S. Department of Energy, Nevada Operations Office (DOE/NV), in support of the Nevada Environmental Restoration Project (NV ERP) at the Nevada Test Site. IT Corporation (IT) was the principal environmental contractor for the project. The roles and responsibilities of IT and other contractors involved in the project are described in the Raytheon Services Nevada (RSN) Drilling Program and the Underground Test Area Operable Unit Project Management Plan. The well will become part of the Underground Test Area (UGTA) monitoring well network.

  9. An Er:YAG blood sampling skin puncher

    NASA Astrophysics Data System (ADS)

    Savastru, D.; Ristici, Esofina; Mustata, Marina; Miclos, S.; Rusu, M.; Radu, C.; Savu, V.

    2007-08-01

    Generally, the beam distribution in the tissue in interaction with a pulsed laser is defined by the optical properties (effective scattering and absorption coefficient). A special Er:YAG device used for blood sampling without any pain is presented. Our device emitting on 2940 nm has a special function. It can give four energy levels for four types of skin. At 3000 nm there is an absorption peak in water, and the absorption in tissue is intense and the vaporization is immediate and superficial without surrounding damages. Additionally, the very short duration of the pulse (a few hundred microseconds) avoids the phenomenon of thermal diffusion.

  10. ER-2 mountain wave encounter over Antarctica - Evidence for blocking

    NASA Technical Reports Server (NTRS)

    Bacmeister, Julio T.; Schoeberl, Mark R.; Lait, Leslie R.; Newman, Paul A.; Gary, Bruce

    1990-01-01

    Orographically forced large-amplitude gravity waves (mountain waves) encountered during the AAOE experiment by ER-2 on September 22, 1987 over Alexander Island (73-70 deg W, 69-72 deg S) were analyzed using a three-dimensional steady-state model of stratified flow over realistic topography, similar to the model used by Smith (1980). Taking into account the effects of low-level flow blocking, reasonable agreement was obtained between the model and observations, indicating that blocking may be an important feature of real flow over topography.

  11. Pyogenic Granuloma: Surgical Treatment with Er:YAG Laser

    PubMed Central

    Fekrazad, Reza; Nokhbatolfoghahaei, Hanieh; Khoei, Farzaneh; Kalhori, Katayoun AM

    2014-01-01

    Introduction: Pyogenic granuloma (PG) is a common tumor-like growth of the oral cavity, considered to be of non-neoplastic nature, often caused by constant low-grade trauma as well as poor oral hygiene and maybe due to hormonal disturbances. Surgical excision, and removal of underlying cause in some cases, is the preferred method of treatment as it is only a benign lesion.In order to remove this lesion, scalpel, cryosurgery and laser are used. Currently different lasers, with adequate parameters, are used for the surgery of PG, which include CO2 (Carbon Dioxide Laser), Nd:YAG (Neodymium-Doped Yttrium Aluminium Garnet), Diode and Er Family amongst others. In this present case, due to the proximity of the lesion with dental hard tissue, Er:YAG (Erbium-Doped Yttrium Aluminum Garnet) laser appears to be the more appropriate laser. The application of Laser is also a newly recommended technique. The aim of this study is to assess the stages of treatment, recovery and recurrence of PG when the Er:YAG laser is used. Furthermore this study aims to also evaluate the friendliness of this method with regards to the surgeon (therapist). Case report: A 24-year-old female was referred to the Laser Research Center of Dentistry of Tehran University of Medical Sciences with a complaint of gingival overgrowth and bleeding. This lesion was in the buccal and palatal side of the 5 and 6 maxillary teeth. Treatment plan included an excisional biopsy of the lesion using Er:YAG laser (3W, 300mJ, 10Hz, Short pulse, with contact headpiece). The bones were then cleaned of soft tissue before being smoothed using a curette. The excised specimen was preserved and sent for histopathological examination. Results: The patient reported no pain after surgery and did not use any systemic antibiotics. The patient was satisfied after the surgery. Chlorhexidine mouthwash was given to the patient. Pathology results confirmed Pyogenic granuloma.After 2 weeks, complete healing was observed. The 9-month follow-up was also carried out in order to check the process of healing as well as the recurrence. Conclusion: Excisional surgery is the preferred treatment method for PG. The application of laser can be considered as an effective and safe technique for excision of this lesion with minimal invasion and many clinical advantages such as less intra-operative bleeding, hemostasis and reduced pain and times of healing. PMID:25653822

  12. A sex attractant for the scarab beetle Anomala solida Er.

    PubMed

    Tth, Mikls; Subchev, Mitko; Sredkov, Ivan; Szarukn, Istvn; Leal, Walter

    2003-07-01

    (R, Z)-5-(-)-(Oct-1-enyl)oxacyclopentan-2-one (R-buibuilactone) attracted male Anomala solida Er. (Coleoptera: Scarabaeidae, Rutelinae), a vineyard and orchard pest in Southeastern Europe. The presence of the corresponding (S) enantiomer or of 2-(E)-nonen-1-ol (a frequently found pheromone component in other Anomala spp.) in the bait did not influence catches. Traps baited with (R, Z)-5-(-)-(oct-1-enyl)oxacyclopentan-2-one were successfully used for monitoring the flight of A. solida, and may have practical applications for detection, monitoring, and mass trapping of the pest. PMID:12921442

  13. ER? and ER? Differentially Regulate NKT and V?4+ T-cell Activation and T-regulatory Cell Response in Coxsackievirus B3 Infected Mice

    PubMed Central

    Huber, Sally

    2016-01-01

    Objectives Coxsackievirus B3 (CVB3) induced myocarditis is sex dependent with males developing more severe disease than females. Previous studies had shown that sex-associated hormones determine the sex bias with testosterone and progesterone promoting myocarditis while estrogen (E2) is protective. There are two major estrogen receptors: estrogen receptor alpha (ER?) and estrogen receptor beta (ER?). The goal of the current study was to determine the relative role of these receptors to myocarditis susceptibility and the mechanism of their action. Methods Female C57Bl/6 wild-type mice and C57Bl/6 mice deficient in ER?, or ER? were infected intraperitoneally with 102 plaque forming units CVB3. After 7 days, hearts were evaluated for virus titers by plaque forming assay and myocardial inflammation. Lymphoid cells either from the spleen or infiltrating the heart were characterized by labeling with antibodies including CD4, CD25, FoxP3, IFN?, IL-4, CD11b, CD1d, V?4, TCR?, or with CD1d-tetramer and evaluated by flow cytometry. To confirm that signaling through distinct estrogen receptors controlled myocarditis susceptibility and T-regulatory cell response, male C57Bl/6 mice were treated with the ER?-specific agonist, propyl pyrazole triol (PPT), ER? agonist, diarylpropionitrile (DPN), or 17-?-estradiol (E2) as a non-specific estrogen receptor agonist. Results Myocarditis, cardiac virus titers, and CD4+ Th1 (IFN?) bias were increased in infected ER?KO and decreased in infected ER?KO mice compared to C57Bl/6 controls. CD4+Th1 bias and myocarditis severity correlated inversely with numbers of CD4+CD25+FoxP3+ T regulatory cells which were decreased in ER?KO and increased in ER?KO mice. Increased T-regulatory cells corresponded to a preferential activation of natural killer T (NKT) cells in ER?KO mice. Male C57Bl/6 mice treated with DPN showed increased myocarditis while those treated with PPT and E2 showed decreased myocarditis corresponding to either decreased (DPN) or increased (PPT/E2) T-regulatory cell responses in male C57Bl/6 mice. DPN and PPT treatment had no effect on T-regulatory cell responses in NKT KO or ??KO mice. Conclusion These results demonstrate that ER? and ER? both modulated CVB3 myocarditis susceptibility but in opposite directions and that their predominant effect is mediated through their ability to alter NKT and V?4+ innate T cell responses in the infected host. It is these innate T cells which positively or negatively modulate T-regulatory cell responses.

  14. Estrogen Receptor ? Is Coexpressed with ER? and PR and Associated with Nodal Status, Grade, and Proliferation Rate in Breast Cancer

    PubMed Central

    Jrvinen, Tero A. H.; Pelto-Huikko, Markku; Holli, Kaija; Isola, Jorma

    2000-01-01

    The role of estrogen (ER) and progesterone receptors (PR) in breast cancer is well established. Identification of the second human estrogen receptor, the estrogen receptor ? (ER?), prompted us to evaluate its role in breast cancer. We studied the expression of ER? by immunohistochemistry and mRNA in situ hybridization in 92 primary breast cancers and studied its association with ER?, PR, and various other clinicopathological factors. Sixty percent of tumors were defined as ER?-positive (nuclear staining in >20% of the cancer cells). Normal ductal epithelium and 5 of 7 intraductal cancers were also found to express ER?. Three-fourths of the ER?- and PR-positive tumors were positive for ER?, whereas ER? and PR were positive in 87% and 67% of ER?-positive tumors, respectively. ER? was associated with negative axillary node status (P < 0.0001), low grade (P = 0.0003), low S-phase fraction (P = 0.0003), and premenopausal status (P = 0.04). In conclusion, the coexpression of ER? with ER? and PR as well as its association with the other indicators of low biological aggressiveness of breast cancer suggest that ER?-positive tumors are likely to respond to hormonal therapy. The independent predictive value of ER? remains to be established. PMID:10623650

  15. Highly sensitive alcohol sensor based on a single Er-doped In2O3 nanoribbon

    NASA Astrophysics Data System (ADS)

    Qin, Zhaojun; Liu, Yingkai; Chen, Weiwu; Ai, Peng; Wu, Yuemei; Li, Shuanghui; Yu, Dapeng

    2016-02-01

    Pure In2O3 NBs and Er-In2O3 NBs have been successfully synthesized by carbon thermal reduction. The doping of Er leads the optimal temperature of the In2O3 to decrease. The response of the Er-In2O3 sensor to 100 ppm of alcohol is 4.8 at 220 C, which is twice larger than that of the pure In2O3 sensor. It is also found that the doping of Er has increased the performance of the sensors. Moreover, Er-In2O3 sensor has a fast response (recovery) time to different concentration of alcohol at 220 C. In addition, the mechanism of pure In2O3 sensor and Er-In2O3 sensor are discussed.

  16. Emerging themes of ER organization in the development and maintenance of axons

    PubMed Central

    Renvois, Benot; 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

  17. Translating endoplasmic reticulum biology into the clinic: a role for ER-targeted natural products?

    PubMed

    Pereira, David M; Valento, Patrcia; Correia-da-Silva, Georgina; Teixeira, Natrcia; Andrade, Paula B

    2015-05-01

    ER stress has been identified as a hallmark, and sometimes trigger, of several pathologies, notably cancer, inflammation and neurodegenerative diseases like Alzheimer's and Parkinson's. Among the molecules described in literature known to affect ER function, the majority are natural products, suggesting that natural molecules may constitute a significant arsenal of chemical entities for modulating this cellular target. In this review, we will start by presenting the current knowledge of ER biology and the hallmarks of ER stress, thus paving the way for presenting the natural products that have been described as being ER modulators, either stress inducers or ER protectors. The chemistry, distribution and mechanism of action of these compounds will be presented and discussed. PMID:25703279

  18. ErAsSb nanoparticle growth on GaAs surface by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Zhang, Yuanchang; Eyink, Kurt G.; Peoples, Joseph; Mahalingam, Krishnamurthy; Hill, Madelyn; Grazulis, Larry

    2016-02-01

    ErAsSb nanoparticle (NP) growth is investigated on GaAs surface by molecular beam epitaxy. ErAsSb NP grown under Sb flux is compared to pure ErAs NP grown under As flux. It is found the incorporation of Sb is rather low in ErAsSb. However, ErAsSb NP exhibits very different structural and optical properties. ErAsSb NPs on GaAs preferentially elongates along the [1-10] direction with increasing deposition and growth temperature. The absorption peak for light polarized parallel to the long axis of the particles is found to occur at longer wavelengths than those for light polarized perpendicular to the long axis of the particles. The results can be attributed to Sb surfactant effect.

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

    NASA Astrophysics Data System (ADS)

    Dputier, S.; Guivarc'h, A.; Caulet, J.; Minier, M.; Gurin, 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 dpose dans des conditions d'ultra-vide et des substrats de GaAs orients (001) et (111) ont t tudies aprs des traitements thermiques d'une heure entre 350 et 800 ^{circ}C. L'utilisation de techniques complmentaires d'analyse (RBS, diffraction X) a permis de mettre en vidence, en fonction de la temprature de recuit, plusieurs tapes successives d'interaction correspondant des mlanges de phases, essentiellement des binaires. Elles dpendent fortement de l'orientation du substrat de GaAs, en particulier l'tape finale des interactions. Sur GaAs (001), seules deux tapes ont t observes : avant 600 ^{circ}C, il n'y a pas d'interaction visible de l'erbium avec le substrat ; celle-ci ne s'amorce qu' 600 ^{circ}C pour n'voluer ensuite que faiblement et conduire, 800 ^{circ}C, une composition nominale " Er{10}GaAs ", mlange des phases Er5Ga3 + Er + ErAs. Sur GaAs (111), plusieurs tapes d'interaction sont observes : l'erbium ragit avec le substrat ds 400 ^{circ}C (mlange des phases Er5Ga3 + Er), puis l'interaction se poursuit 600 ^{circ}C (mlange Er5Ga3 + Er + ErAs) avant d'atteindre 800 ^{circ}C la composition nominale " Er{1,5}GaAs ", constitue d'un mlange de grains des trois binaires ErAs + ErGa2 + Er3Ga5. Il faut noter que le recuit 800 ^{circ}C n'est pas suffisant pour atteindre le mlange de phases Ga + ErAs qui, selon le diagramme ternaire, devrait tre le stade ultime de l'interaction Er/GaAs. L'analyse des interdiffusions Er/GaAs montre que ErAs est le compos " cl " autour duquel pivote l'interaction Er/GaAs. Ce compos apparat comme un candidat idal pour la ralisation d'htrostructures pitaxies ErAs/GaAs.

  20. Magnetic properties and transformation of crystal structure in the ErFe{sub 2}-ErAl{sub 2} system

    SciTech Connect

    Ćwik, J. Miller, M.; Koshkid'ko, Y.; Mikhailova, A.; Kolchugina, N.; Nenkov, K.; Hackamer, A.

    2015-03-28

    The modification of structural properties and magnetic behaviour of the ErFe{sub 2−x}Al{sub x} Laves phase intermetallic compounds have been studied while changing the Al content in the range 0.36 ≤ x ≤ 1.5. Powder X-ray diffraction study at room temperature showed the formation of the cubic C15 structure, in the samples with Al content of 0.36 ≤ x < 0.75 and 1.4 ≤ x ≤ 2.0. For the intermediate compositions with 0.75 ≤ x ≤ 1.4, the hexagonal C14 structure is observed. Magnetic and magnetocaloric properties of polycrystalline ErFe{sub 2−x}Al{sub x} intermetallic compounds were investigated experimentally using magnetic and heat capacity measurements. The Curie temperature T{sub C} decreases from 275 to 28 K as the Al content increases from x = 0.36 to x = 1.5, respectively. Magnetization measurements in strong magnetic fields showed the complex mechanism of magnetic saturation in the studied compounds. Under an external field change from 0 to 2 T, the maximum entropy change is 6 J/kg K at T = 28 K for the composition with x = 1.5. The minimum in the concentration dependence of the magnetic entropy change is observed in the vicinity of x equal to 1.25. Regularities of variations of magnetocaloric properties of ErFe{sub 2−x}Al{sub x} intermetallic compounds with increasing Al content are discussed from the point of view of their both structural and magnetic states.

  1. Structure and radiation effect of Er-stuffed pyrochlore Er2(Ti2-xErx)O7-x/2 (x = 0-0.667)

    NASA Astrophysics Data System (ADS)

    Yang, D. Y.; Xu, C. P.; Fu, E. G.; Wen, J.; Liu, C. G.; Zhang, K. Q.; Wang, Y. Q.; Li, Y. H.

    2015-08-01

    Er-stuffed pyrochlore series Er2(Ti2-xErx)O7-x/2 (x = 0, 0.162, 0.286, 0.424 and 0.667) were synthesized using conventional ceramic processing procedures. The structure of Er2(Ti2-xErx)O7-x/2 is effectively tailored by the Er stuffing level (x). In order to study the radiation effect of Er-stuffed pyrochlores, irradiation experiments were performed with 400 keV Ne2+ ions to fluences ranging from 5 × 1014 to 3.0 × 1015 ions/cm2 at cryogenic condition. Irradiation induced microstructural evolution was examined using a grazing incidence X-ray diffraction technique. It is found that the irradiated layer of Er2(Ti2-xErx)O7-x/2 undergoes significant lattice disordering and swelling at fluences of ⩽1.5 × 1015 ions/cm2 and amorphization at fluences of ⩾1.5 × 1015 ions/cm2. The radiation effect depends strongly on the chemical compositions of the samples. Both the lattice swelling percentage and the amorphous fraction decrease with increasing x. The experimental results are discussed in the context of cation antisite defect. The defect formation energy which varies as a function of x is responsible for the difference in the structural behaviors of Er2(Ti2-xErx)O7-x/2 under 400 keV Ne2+ ion irradiation.

  2. 20 CFR 218.13 - When a widow(er) annuity begins.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false When a widow(er) annuity begins. 218.13 Section 218.13 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ANNUITY BEGINNING AND ENDING DATES When an Annuity Begins § 218.13 When a widow(er) annuity begins. (a) A widow(er) annuity begins on the later...

  3. 20 CFR 216.61 - Who is eligible for an annuity as a widow(er).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Who is eligible for an annuity as a widow(er). 216.61 Section 216.61 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ELIGIBILITY FOR AN ANNUITY Widow(er), Surviving Divorced Spouse, and Remarried Widow(er) Annuities § 216.61 Who is eligible for...

  4. ER? expression and breast cancer risk prediction for women with atypias.

    PubMed

    Hieken, Tina J; Carter, Jodi M; Hawse, John R; Hoskin, Tanya L; Bois, Melanie; Frost, Marlene; Hartmann, Lynn C; Radisky, Derek C; Visscher, Daniel W; Degnim, Amy C

    2015-11-01

    Estrogen receptor (ER) ? is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ER? expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ER? expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967-1991. Nuclear ER? percent and intensity was scored in the atypia and adjacent normal lobules. An ER? sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ER? expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ER? expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ER? expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ER? expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low-moderate ER? expression (P = 0.0008). High ER? expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ER? may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction. PMID:26276747

  5. 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.

  6. Intra-ER sorting of the peroxisomal membrane protein Pex3 relies on its luminal domain

    PubMed Central

    Fakieh, Mohammad H.; Drake, Peter J. M.; Lacey, Joanne; Munck, Joanne M.; Motley, Alison M.; Hettema, Ewald H.

    2013-01-01

    Summary Pex3 is an evolutionarily conserved type III peroxisomal membrane protein required for peroxisome formation. It is inserted into the ER membrane and sorted via an ER subdomain (the peroxisomal ER, or pER) to peroxisomes. By constructing chimeras between Pex3 and the type III ER membrane protein Sec66, we have been able to separate the signals that mediate insertion of Pex3 into the ER from those that mediate sorting within the ER to the pER subdomain. The N-terminal 17-amino acid segment of Pex3 contains two signals that are each sufficient for sorting to the pER: a chimeric protein containing the N-terminal domain of Pex3 fused to the transmembrane and cytoplasmic segments of Sec66 sorts to the pER in wild type cells, and does not colocalise with peroxisomes. Subsequent transport to existing peroxisomes requires the Pex3 transmembrane segment. When expressed in Drosophila S2R+ cells, ScPex3 targeting to peroxisomes is dependent on the intra-ER sorting signals in the N-terminal segment. The N-terminal segments of both human and Drosophila Pex3 contain intra-ER sorting information and can replace that of ScPex3. Our analysis has uncovered the signals within Pex3 required for the various steps of its transport to peroxisomes. Our generation of versions of Pex3 that are blocked at each stage along its transport pathway provides a tool to dissect the mechanism, as well as the molecular machinery required at each step of the pathway. PMID:23951409

  7. 20 CFR 218.40 - When a widow(er) annuity ends.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false When a widow(er) annuity ends. 218.40 Section... ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends 218.40 When a widow(er) annuity ends. (a) Entitlement based on age. When a widow(er)'s annuity is based on age, the annuity ends with the earliest...

  8. 20 CFR 218.40 - When a widow(er) annuity ends.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true When a widow(er) annuity ends. 218.40 Section... ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends 218.40 When a widow(er) annuity ends. (a) Entitlement based on age. When a widow(er)'s annuity is based on age, the annuity ends with the earliest...

  9. 20 CFR 218.40 - When a widow(er) annuity ends.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true When a widow(er) annuity ends. 218.40 Section... ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends 218.40 When a widow(er) annuity ends. (a) Entitlement based on age. When a widow(er)'s annuity is based on age, the annuity ends with the earliest...

  10. 20 CFR 218.40 - When a widow(er) annuity ends.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When a widow(er) annuity ends. 218.40 Section... ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends 218.40 When a widow(er) annuity ends. (a) Entitlement based on age. When a widow(er)'s annuity is based on age, the annuity ends with the earliest...

  11. 20 CFR 218.40 - When a widow(er) annuity ends.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false When a widow(er) annuity ends. 218.40 Section... ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends 218.40 When a widow(er) annuity ends. (a) Entitlement based on age. When a widow(er)'s annuity is based on age, the annuity ends with the earliest...

  12. Intra-ER sorting of the peroxisomal membrane protein Pex3 relies on its luminal domain.

    PubMed

    Fakieh, Mohammad H; Drake, Peter J M; Lacey, Joanne; Munck, Joanne M; Motley, Alison M; Hettema, Ewald H

    2013-08-15

    Pex3 is an evolutionarily conserved type III peroxisomal membrane protein required for peroxisome formation. It is inserted into the ER membrane and sorted via an ER subdomain (the peroxisomal ER, or pER) to peroxisomes. By constructing chimeras between Pex3 and the type III ER membrane protein Sec66, we have been able to separate the signals that mediate insertion of Pex3 into the ER from those that mediate sorting within the ER to the pER subdomain. The N-terminal 17-amino acid segment of Pex3 contains two signals that are each sufficient for sorting to the pER: a chimeric protein containing the N-terminal domain of Pex3 fused to the transmembrane and cytoplasmic segments of Sec66 sorts to the pER in wild type cells, and does not colocalise with peroxisomes. Subsequent transport to existing peroxisomes requires the Pex3 transmembrane segment. When expressed in Drosophila S2R+ cells, ScPex3 targeting to peroxisomes is dependent on the intra-ER sorting signals in the N-terminal segment. The N-terminal segments of both human and Drosophila Pex3 contain intra-ER sorting information and can replace that of ScPex3. Our analysis has uncovered the signals within Pex3 required for the various steps of its transport to peroxisomes. Our generation of versions of Pex3 that are blocked at each stage along its transport pathway provides a tool to dissect the mechanism, as well as the molecular machinery required at each step of the pathway. PMID:23951409

  13. 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 = 1321) and 5 per 100000 women (model range = 36) 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

  14. LOCAL TRANSLATION. Comment on "Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling".

    PubMed

    Reid, David W; Nicchitta, Christopher V

    2015-06-12

    Jan et al. (Research Articles, 7 November 2014, p. 716) propose that ribosomes translating secretome messenger RNAs (mRNAs) traffic from the cytosol to the endoplasmic reticulum (ER) upon emergence of the signal peptide and return to the cytosol after termination. An accounting of controls demonstrates that mRNAs initiate translation on ER-bound ribosomes and that ribosomes are retained on the ER through many cycles of translation. PMID:26068841

  15. MappERS-C and MappERS-V. The crowd source for prevention and crisis support

    NASA Astrophysics Data System (ADS)

    Frigerio, Simone; Schenato, Luca; Bianchizza, Chiara; Del Bianco, Daniele

    2015-04-01

    The responsibilities within natural hazards at local/regional levels involve citizens and volunteers as first actors of civil protection and territorial management. The prevention implicates the capacities of professional operators and technical volunteers, but the priority implies now the involvement and awareness of the citizens over the territory they inhabit. The involvement of population creates context-specific strategies of territorial surveillance and management, skipping the limit to face risks only when they have to bear impacts on their lives. MAppERS (Mobile Application for Emergency Response and Support) is a EU project (funded under programme 2013-2015 Humanitarian Aid and Civil Protection, ECHO A5) which empowers "crowd-sourced mappers" through smart phone applications and sensors, with geo-tagged information, detailed gathered parameters, field-check survey in a contest of geospatial response. The process of development includes feedback from citizens, involving them in training courses on the monitoring as long term objective (raising public awareness and participation). The project deals with the development and testing of the smart phone applications (module MAppERS-V for volunteers, module MAppERS-C for citizens) according to Android SDK environment. A first research described a desk-based investigation on consequences of disasters impacts and costs of prevention strategies in pilot countries. Furthermore a review of state-of-the-art of database management systems (DBMS) in pilot countries and involvement of volunteers/citizens in data collection/monitoring collected basic info on data structure for the development. A desk-based research proposed communication methods/graphic solutions within mobile technologies for disaster management in pilot countries and available smartphone applications linked to centralized web/server database. A technical review is compulsory for a useful design-line for MappERS development, and it is linked with on-site feedback about volounteers and citizens needs within pilot groups activities. The app modules will be later re-designed according to the methodological and technical feedback gained during pilot study. Training curricula for citizens are planned to increase awareness, skills on smart phone utilities and efficient jargon for hazard contest. The expected results are: a) an easy-to-use interface for "human-data" in crisis support, b) a maximised utility of peer-produced data gathering, c) the development of human resources as technical tools d) a self-based awareness improvement.

  16. Completion Report for Well ER-8-1

    SciTech Connect

    Bechtel Nevada

    2004-11-01

    Well ER-8-1 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well was drilled in October and November of 2002 as part of a Hydrogeologic investigation program for the Yucca Flat/Climax Mine Corrective Action Unit in the northeastern portion of the Nevada Test Site. Well ER-8-1 is located at the north end of Yucca Flat approximately 580 meters south-southeast of the surface exposure of the Climax granitic intrusive. Detailed lithologic descriptions with stratigraphic assignments are included in this report. These are based on composite drill cuttings samples collected every 3 meters, and 21 sidewall samples taken at various depths between 351.1 and 573.0 meters, supplemented by incomplete geophysical log data. Detailed petrographic, geochemical, and mineralogical studies of rock samples were conducted on 22 samples of drill cuttings. Drilling began in tuffaceous alluvium, and the borehole penetrated Tertiary age bedded tuffs of the Volcanics of Oak Spring Butte and carbonate sediments of Paleozoic age, which were encountered at a depth of 334 meters. The borehole unexpectedly penetrated granite at the depth of 538.9 meters in which drilling was stopped. Contact metamorphic rocks and intrusive dikes associated with the Cretaceous-age granitic intrusive and at least one significant fault zone were encountered.

  17. Er,Cr:YSGG Pulsed laser applied to medical dentistry

    NASA Astrophysics Data System (ADS)

    Beltrano, J. J.; Torrisi, L.; Campagna, E.; Rapisarda, E.; Finocchiaro, I.; Olivi, G.

    An erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) pulsed laser, operating at 2780 ? m wavelength, 300 mJ maximum pulse energy, 140 ? s pulse duration and 20 Hz repetition rate, was employed to irradiate human teeth. The photon energy is transmitted to the tooth through an optical fiber with a sapphire tip, which is dipped in an adjustable air/water atomizer spray. Extracted teeth were cleaned in an ultrasonic bath, stored in saline solution, and dried and weighed before each laser treatment. The laser irradiation was performed for 10 s using a 600 ? m focused beam. Each sample was irradiated varying the air/water ratio of the integrated nebulizer spray. After the treatment, the samples were again weighed and produced craters were analyzed with a profilometric system. The crater volume permitted to evaluate the laser ablation yield. Teeth treated with an air/water spray ratio of 95-80% resulted in greatest average quantity of tissue ablation. This investigation confirmed the high efficiency of the Er,Cr:YSGG laser in the ablation of dental hard tissues showing the fundamental role of the water spray, which plays a fundamental role in the quantitative and qualitative modifications of the hard tissue treated, as it will be discussed in detail.

  18. ER-to-mitochondria miscommunication and metabolic diseases.

    PubMed

    Lpez-Crisosto, Camila; Bravo-Sagua, Roberto; Rodriguez-Pea, Marcelo; Mera, Claudia; Castro, Pablo F; Quest, Andrew F G; Rothermel, Beverly A; Cifuentes, Mariana; Lavandero, Sergio

    2015-10-01

    Eukaryotic cells contain a variety of subcellular organelles, each of which performs unique tasks. Thus follows that in order to coordinate these different intracellular functions, a highly dynamic system of communication must exist between the various compartments. Direct endoplasmic reticulum (ER)-mitochondria communication is facilitated by the physical interaction of their membranes in dedicated structural domains known as mitochondria-associated membranes (MAMs), which facilitate calcium (Ca(2+)) and lipid transfer between organelles and also act as platforms for signaling. Numerous studies have demonstrated the importance of MAM in ensuring correct function of both organelles, and recently MAMs have been implicated in the genesis of various human diseases. Here, we review the salient structural features of interorganellar communication via MAM and discuss the most common experimental techniques employed to assess functionality of these domains. Finally, we will highlight the contribution of MAM to a variety of cellular functions and consider the potential role of MAM in the genesis of metabolic diseases. In doing so, the importance for cell functions of maintaining appropriate communication between ER and mitochondria will be emphasized. PMID:26171812

  19. ER Consolidated Qtrly Rpt_July-September 2015_January 2016

    SciTech Connect

    Cochran, John R.

    2016-01-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the July, August, and September 2015 quarterly reporting period. The Solid Waste Management Units (SWMUs) and Areas of Concern (AOCs) identified for corrective action at SNL/NM are listed in Table I-1. The work completed during this quarter is reported below in Sections I.2.1 and I.2.2. Section I.2.1 summarizes the quarterly activities at sites undergoing corrective action field activities (SWMUs 8 and 58, 68, 149, 154, and 502, and three groundwater AOCs). Section I.2.2 summarizes quarterly activities at sites where the New Mexico Environment Department (NMED) has issued a certificate of completion and the site is in the corrective action complete (CAC) regulatory process. Currently, the Mixed Waste Landfill (MWL, SWMU 76) is the only site in the CAC regulatory process. Corrective action activities have been deferred at the Long Sled Track (SWMU 83), the Gun Facilities (SWMU 84), and the Short Sled Track (SWMU 240) because these are active mission facilities.

  20. Population dynamics in Er3+-doped fluoride glasses

    NASA Astrophysics Data System (ADS)

    Bogdanov, V. K.; Booth, D. J.; Gibbs, W. E.; Javorniczky, J. S.; Newman, P. J.; Macfarlane, D. R.

    2001-05-01

    A detailed study of the energy-transfer processes in Er3+: flouride glasses with doping concentrations of 0.2-18 mol % is presented. Fluorescence wave forms for 11 erbium transitions were measured under 802-nm, 1.5-?m, 975-nm, 520-nm, and 403-nm excitation from a high-energy short-pulse source. The analysis of these data provided a physical understanding of the processes responsible for the temporal behavior of the populations of a large number of energy levels. A comprehensive nine-level rate-equation model of the Er3+ population dynamics in these fluoride glasses is developed. The model performs well in predicting the observed fluorescence behavior of the main fluorescing lines under all pumping conditions. The modeling process allowed 14 ion-ion energy-transfer processes that are important for the population dynamics in these fluoride glasses to be identified and their rate constants obtained. Noticeably, the inclusion of seven three-ion processes was found necessary in order to obtain good fits to the experimental fluorescence wave forms. It was also found that some three-ion processes have a significant effect on the population dynamics of the levels even in lower doping concentrations.

  1. Fractional Er:YAG laser and its application in dermatology

    NASA Astrophysics Data System (ADS)

    Fan, XiaoHong; Li, Zhengjia; Zhou, Hai; He, YanYan; Xia, HongXing

    2008-12-01

    Fractional laser resurfacing technology is one of those medical advanced technologies. It has bridged the gap between ablative lasers and non-ablative lasers. Fractional laser resurfacing is a new laser skin treatment modality that creates numerous microscopic thermal injury zones with controlled width, depth and density. Those injury zones are surrounded by a reservoir of spared epidermal and dermal tissue that allow for rapid repair of laser-induced thermal injury. In this paper the ideal laser parameters, the damage depth and width, the relationship between the energy and the damage about fractional resurfacing and so on are analyzed. The results show: the Q-switch Er:YAG laser is an ideal lasers for fractional laser resurfacing, the dynamical equilibrium time of fractional resurfacing treating is depended on the energy, the damage area is only the evaporation zone with minimal residual heat, and the damage width and depth of the injury zone in fractional treating can be controlled precisely by the appropriate adjustment of the diameter, energy, pulse width and frequency of Er:YAG laser beam.

  2. Compact pulsed high-energy Er:glass laser

    NASA Astrophysics Data System (ADS)

    Wan, Peng; Liu, Jian

    2012-03-01

    Bulk Erbium-doped lasers are widely used for long-distance telemetry and ranging. In some applications such as coherent Doppler radars, laser outputs with a relatively long pulse width, good beam profile and pulse shape are required. High energy Q-switched Er:glass lasers were demonstrated by use of electro-optic (E/O) Q-switching or frustrated total internal reflection (FTIR) Q-switching. However, the output pulse durations in these lasers were fixed to relatively small values and extremely hard to tune. We report here on developing a novel and compact Q-switched Er:Yb co-doped phosphate glass laser at an eye-safe wavelength of 1.5 μm. A rotating mirror was used as a Q-switch. Co-linear pump scheme was used to maintain a good output beam profile. Near-perfect Gaussian temporal shape was obtained in our experiment. By changing motor rotation speed, pulse duration was tunable and up to 240 ns was achieved. In our preliminary experiment, output pulse energies of 44 mJ and 4.5 mJ were obtained in free-running and Q-switched operation modes respectively.

  3. Completion Report for Well ER-2-1

    SciTech Connect

    Bechtel Nevada

    2004-10-01

    Well ER-2-1 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (formerly Nevada Operations Office), in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well was drilled in February and March of 2003, as part of a hydrogeologic investigation program for the Yucca Flat/Climax Mine Corrective Action Unit in the northeastern portion of the Nevada Test Site. Well ER-2-1 was drilled as part of the Yucca Flat Corrective Action Unit Phase I drilling initiative. The well is located in north central Yucca Flat within Area 2 of the Nevada Test Site, and provided information regarding the radiological and physical environment near underground nuclear tests conducted in a saturated volcanic aquifer setting. Detailed lithologic descriptions with stratigraphic assignments are included in this report. These are based on composite drill cuttings collected every 3 meters and 83 sidewall samples taken at various depths between 113.7 and 754.4 meters, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies of rock samples were conducted on 27 samples of drill cuttings. The well was collared in tuffaceous alluvium, and penetrated Tertiary-age tuffs of the Timber Mountain and Paintbrush Groups, Calico Hills and Wahmonie Formations, Crater Flat Group, Grouse Canyon Formation, before reaching total depth in the Tunnel Bed Formation.

  4. Modeling of Yb3+/Er3+-codoped microring resonators

    NASA Astrophysics Data System (ADS)

    Valls, Juan A.; G?l?tu?, Ramona

    2015-03-01

    The performance of a highly Yb3+/Er3+-codoped phosphate glass add-drop microring resonator is numerically analyzed. The model assumes resonant behaviour of both pump and signal powers and the dependences of pump intensity build-up inside the microring resonator and of the signal transfer functions to the device through and drop ports are evaluated. Detailed equations for the evolution of the rare-earth ions levels population densities and the propagation of the optical powers inside the microring resonator are included in the model. Moreover, due to the high dopant concentrations considered, the microscopic statistical formalism based on the statistical average of the excitation probability of the Er3+ ion in a microscopic level has been used to describe energy-transfer inter-atomic mechanisms. Realistic parameters and working conditions are used for the calculations. Requirements to achieve amplification and laser oscillation within these devices are obtainable as a function of rare earth ions concentration and coupling losses.

  5. The Application of Survey in ER Wang Temple Restituting

    NASA Astrophysics Data System (ADS)

    Shuai, W.; Rong, Z.

    2013-07-01

    Er Wang Temple, in World Heritage Site "Dujiang Weirs and Qingchengshan Mountai", was severely destroyed in Wenchuan earthquake of May 2008. There are several problems at different level in every building, such as structural distortion, foundation displacement, wall fracture, roof damage, etc. The stage was completely collapsed in the earthquake. Tableland the stage situated had a huge crack and slope collapse. This article is for the stage renovation. The survey of damage in earthquake is the basis of Er Wang Temple restituting. Survey including field survey after the earthquake and the measurement and investigation for the remained construction member of the main wood structure. For field survey, the basis of pillars which had not have significantly affects in earthquake could be seem as the reference points for measurement. The investigation of remained main wood construction member, especially the size of the key structures and site and manufacture method of the joints, is the important basis for recovery stage. Our team did our utmost to restore the original appearance of stage in design, materials and craft by various tools, which include measured drawings in different times, old images collection, fine measuring by 3D laser scan, measurement of leftover pieces, logical inference.

  6. Specific features of the nonradiative relaxation of Er{sup 3+} ions in epitaxial Si structures

    SciTech Connect

    Kudryavtsev, K. E. Kryzhkov, D. I.; Antonov, A. V.; Shengurov, D. V.; Shmagin, V. B.; Krasilnik, Z. F.

    2014-12-15

    The specific features of the nonradiative relaxation of Er{sup 3+} ions in Si:Er layers grown by sublimation molecular-beam epitaxy (SMBE) are studied. In Si:Er/Si diode structures containing precipitation-type emitting centers, a resonance photoresponse at the wavelength ? ? 1.5 ?m is observed, which is indicative of the nonradiative relaxation of Er3+ ions via the energy back-transfer mechanism. Saturation of the erbium-related photocurrent is for the first time observed at high temperatures. This allows estimation of the concentration of Er centers that undergo relaxation via the above-mentioned back-transfer mechanism (N{sub 0} ? 5 10{sup 16} cm{sup ?3}). In terms of order of magnitude, the estimated concentration N{sub 0} corresponds to the concentration of optically active Er ions upon excitation of the Si:Er layers by means of the recombination mechanism. The features of the nonradiative relaxation of Er{sup 3+} ions in Si:Er/Si structures with different types of emitting centers are analyzed.

  7. ER? inhibits epithelial-mesenchymal transition by suppressing Bmi1 in breast cancer

    PubMed Central

    Wei, Xiao-Long; Dou, Xiao-Wei; Bai, Jing-Wen; Luo, Xiang-Rong; Qiu, Si-Qi; Xi, Di-Di; Huang, Wen-He; Du, Cai-Wen; Man, Kwan; Zhang, Guo-Jun

    2015-01-01

    In human breast cancer, estrogen receptor-? (ER?) suppresses epithelial-mesenchymal transition (EMT) and stemness, two crucial parameters for tumor metastasis; however, the underlying mechanism by which ER? regulates these two processes remains largely unknown. Bmi1, the polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog, regulates EMT transition, maintains the self-renewal capacity of stem cells, and is frequently overexpressed in human cancers. In the present study, ER? upregulated the expression of the epithelial marker, E-cadherin, in breast cancer cells through the transcriptional down-regulation of Bmi1. Furthermore, ER? overexpression suppressed the migration, invasion, and EMT of breast cancer cells. Notably, overexpression of ER? significantly decreased the CD44high/CD24low cell population and inhibited the capacity for mammosphere formation in ER?-negative breast cancer cells. In addition, overexpression of Bmi1 attenuated the ER?-mediated suppression of EMT and cell stemness. Immunohistochemistry revealed an inverse association of ER? and Bmi1 expression in human breast cancer tissue. Taken together, our findings suggest that ER? inhibits EMT and stemness through the downregulation of Bmi1. PMID:26023734

  8. Charge collection mapping of the back-transfer process in Er-doped silicon

    NASA Astrophysics Data System (ADS)

    Castaldini, A.; Cavallini, A.; Fraboni, B.; Pizzini, S.

    2000-06-01

    Charge collection analyses have been carried out on Er-doped silicon to investigate the excitation and de-excitation mechanisms of the Er3+ ion related to the ?=1.54 ?m luminescence. Carrier recombination and trapping at the defective states induced in the material by the presence of Er play a significant role in the excitation of the Er3+ ion and in its nonradiative decay by the energy back-transfer process. We have obtained a two-dimensional map of the lattice sites where the back-transfer process occurs, and provided experimental proof of the cooperation of two different defects in the excitation and de-excitation processes.

  9. Chaperone gp96 mediates ER-α36 cell membrane expression

    PubMed Central

    Hou, Junwei; Deng, Mengmeng; Li, Xin; Liu, Weiwei; Chu, Xiaoyu; Wang, Jing; Chen, Feng; Meng, Songdong

    2015-01-01

    ER (estrogen receptor)-α36, a variant of human ERα, activates non-genomic cell signaling pathways. ER-α36 on the cell membrane plays a role in breast cancer growth and development, and contributes to tamoxifen resistance. However, it is not understood how cell membrane expression of ER-α36 is regulated. In this study, we investigated the role of cell membrane glycoprotein 96 (mgp96) in the regulation of ER-α36 expression and signaling. We found that the C-terminal domain of mgp96 directly interacts with ER-α36 on the cell membrane of breast tumor cells. This interaction stabilizes the ER-α36 protein, thereby increasing its signaling, which, in turn, increases tumor cell growth and invasion. Moreover, targeting mgp96 with siRNA or monoclonal antibody (mAb) blocks the mgp96-ER-α36 interaction and inhibits breast cancer growth and invasion both in vitro and in vivo. These results provide insights into the modulation of cell membrane ER-α36 expression and suggest that mgp96 could be a potential therapeutic target for ER-α36-overexpressing breast cancer. PMID:26396174

  10. Estrogen induces two distinct cholesterol crystallization pathways by activating ER? and GPR30 in female mice.

    PubMed

    de Bari, Ornella; Wang, Tony Y; Liu, Min; Portincasa, Piero; Wang, David Q-H

    2015-09-01

    To distinguish the lithogenic effect of the classical estrogen receptor ? (ER?) from that of the G protein-coupled receptor 30 (GPR30), a new estrogen receptor, on estrogen-induced gallstones, we investigated the entire spectrum of cholesterol crystallization pathways and sequences during the early stage of gallstone formation in gallbladder bile of ovariectomized female wild-type, GPR30((-/-)), ER?((-/-)), and GPR30((-/-))/ER?((-/-)) mice treated with 17?-estradiol (E2) at 6 g/day and fed a lithogenic diet for 12 days. E2 disrupted biliary cholesterol and bile salt metabolism through ER? and GPR30, leading to supersaturated bile and predisposing to the precipitation of cholesterol monohydrate crystals. In GPR30((-/-)) mice, arc-like and tubular crystals formed first, followed by classical parallelogram-shaped cholesterol monohydrate crystals. In ER?((-/-)) mice, precipitation of lamellar liquid crystals, typified by birefringent multilamellar vesicles, appeared earlier than cholesterol monohydrate crystals. Both crystallization pathways were accelerated in wild-type mice with the activation of GPR30 and ER? by E2. However, cholesterol crystallization was drastically retarded in GPR30((-/-))/ER?((-/-)) mice. We concluded that E2 activates GPR30 and ER? to produce liquid crystalline versus anhydrous crystalline metastable intermediates evolving to cholesterol monohydrate crystals from supersaturated bile. GPR30 produces a synergistic lithogenic action with ER? to enhance E2-induced gallstone formation. PMID:26152119

  11. Hydrothermal synthesis and magnetic properties of ErCrO{sub 4} nanoparticles

    SciTech Connect

    Sundarayya, Y. Kumar, K. Ashwini Sondge, Rajesh Srinath, S. Kaul, S. N.

    2014-04-24

    Homogeneous single phase ErCrO{sub 4} nanoparticles have been synthesized by a modified sol-gel followed by hydrothermal method. X-ray diffraction reveals that the compound crystallizes into tetragonal structure with space group I41/amd. The average crystallite size was estimated to be 21(1) nm. Morphological analysis of the sample confirms uniform particles of size 20 nm. DC magnetic measurements show that ErCrO{sub 4} undergoes a paramagnetic-antiferromagnetic transition at 16 K, due to the superexchange Er-O-Cr-O-Er antiferromagnetic interactions.

  12. TRAM1 is involved in disposal of ER membrane degradation substrates.

    PubMed

    Ng, Caroline L; Oresic, Kristina; Tortorella, Domenico

    2010-08-01

    ER quality control consists of monitoring protein folding and targeting misfolded proteins for proteasomal degradation. ER stress results in an unfolded protein response (UPR) that selectively upregulates proteins involved in protein degradation, ER expansion, and protein folding. Given the efficiency in which misfolded proteins are degraded, there likely exist cellular factors that enhance the export of proteins across the ER membrane. We have reported that translocating chain-associated membrane protein 1 (TRAM1), an ER-resident membrane protein, participates in HCMV US2- and US11-mediated dislocation of MHC class I heavy chains (Oresic, K., Ng, C.L., and Tortorella, D. 2009). Consistent with the hypothesis that TRAM1 is involved in the disposal of misfolded ER proteins, cells lacking TRAM1 experienced a heightened UPR upon acute ER stress, as evidenced by increased activation of unfolded protein response elements (UPRE) and elevated levels of NF-kappaB activity. We have also extended the involvement of TRAM1 in the selective degradation of misfolded ER membrane proteins Cln6(M241T) and US2, but not the soluble degradation substrate alpha(1)-antitrypsin null(HK). These degradation model systems support the paradigm that TRAM1 is a selective factor that can enhance the dislocation of ER membrane proteins. PMID:20430023

  13. ?9-Tetrahydrocannabinol Disrupts Estrogen-Signaling through Up-Regulation of Estrogen Receptor ? (ER?)

    PubMed Central

    Takeda, Shuso; Yoshida, Kazutaka; Nishimura, Hajime; Harada, Mari; Okajima, Shunsuke; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Watanabe, Kazuhito; Omiecinski, Curtis J.; Aramaki, Hironori

    2014-01-01

    ?9-Tetrahydrocannabinol (?9-THC) has been reported as possessing antiestrogenic activity, although the mechanisms underlying these effects are poorly delineated. In this study, we used the estrogen receptor ? (ER?)-positive human breast cancer cell line, MCF-7, as an experimental model and showed that ?9-THC exposures markedly suppresses 17?-estradiol (E2)- induced MCF-7 cell proliferation. We demonstrate that these effects result from ?9-THCs ability to inhibit E2-liganded ER? activation. Mechanistically, the data obtained from biochemical analyses revealed that (i) ?9-THC up-regulates ER?, a repressor of ER?, inhibiting the expression of E2/ER?-regulated genes that promote cell growth and that (ii) ?9-THC induction of ER? modulates E2/ER? signaling in the absence of direct interaction with the E2 ligand binding site. Therefore, the data presented support the concept that ?9-THCs antiestrogenic activities are mediated by the ER? disruption of E2/ER? signaling. PMID:23718638

  14. Examination of ferroelectric and magnetic properties of hexagonal ErFeO3 thin films

    NASA Astrophysics Data System (ADS)

    Yokota, Hiroko; Nozue, Tomoya; Nakamura, Shin; Fukunaga, Mamoru; Fuwa, Akio

    2015-10-01

    Hexagonal ErFeO3 (h-ErFeO3) thin films were fabricated by a pulsed laser deposition method. X-ray diffraction experiments confirmed that single-phase h-ErFeO3 thin films were successfully obtained and were c axis-oriented. Ferroelectricity was confirmed by D-E hysteresis loop measurement at room temperature and the magnitude of spontaneous polarization was estimated to be 200 nC/cm2. A weak ferromagnetism appeared below 120 K and dielectric constants started to exhibit magnetic field dependence. These observations demonstrate the coexistence of ferroelectricity and weak ferromagnetism in h-ErFeO3 thin films.

  15. ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension.

    PubMed

    Young, Colin N; Cao, Xian; Guruju, Mallikarjuna R; Pierce, Joseph P; Morgan, Donald A; Wang, Gang; Iadecola, Costantino; Mark, Allyn L; Davisson, Robin L

    2012-11-01

    Although endoplasmic reticulum (ER) stress is a pathologic mechanism in a variety of chronic diseases, it is unclear what role it plays in chronic hypertension (HTN). Dysregulation of brain mechanisms controlling arterial pressure is strongly implicated in HTN, particularly in models involving angiotensin II (Ang II). We tested the hypothesis that ER stress in the brain is causally linked to Ang II-dependent HTN. Chronic systemic infusion of low-dose Ang II in C57BL/6 mice induced slowly developing HTN, which was abolished by co-infusion of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) into the lateral cerebroventricle. Investigations of the brain regions involved revealed robust increases in ER stress biomarkers and profound ER morphological abnormalities in the circumventricular subfornical organ (SFO), a region outside the blood-brain barrier and replete with Ang II receptors. Ang II-induced HTN could be prevented in this model by selective genetic supplementation of the ER chaperone 78-kDa glucose-regulated protein (GRP78) in the SFO. These data demonstrate that Ang II-dependent HTN is mediated by ER stress in the brain, particularly the SFO. To our knowledge, this is the first report that ER stress, notably brain ER stress, plays a key role in chronic HTN. Taken together, these findings may have broad implications for the pathophysiology of this disease. PMID:23064361

  16. MTA1 regulation of ER? pathway in salivary gland carcinoma cells.

    PubMed

    Ohshiro, Kazufumi; Kumar, Rakesh

    2015-09-01

    Although Metastatic-tumor antigen 1 (MTA1) is differentially expressed in metastatic cancer and coregulates the status and activity of nuclear receptors, its role upon estrogen receptor ? (ER?) - a potent tumor suppressor, remains poorly understood. Here we investigated whether MTA1 regulates the expression and functions of ER?, an ER isoform predominantly expressed in salivary gland cancer cells. We found that the depletion of the endogenous MTA1 in the HSG and HSY salivary duct carcinoma cell lines enhances the expression of ER? while MTA1 overexpression augmented the expression of ER? in salivary duct carcinoma cells. Furthermore, MTA1 knockdown inhibited the proliferations and invasion of HSG and HSY cells. The noted ER? downregulation by MTA1 overexpression involves the process of proteasomal degradation, as a proteasome inhibitor could block it. In addition, both MTA1 knockdown and ER? overexpression attenuated the cell migration and inhibited the ERK1/2 signaling in the both cell lines. These findings imply that MTA1 dysregulation in a subset of salivary gland cancer might promote aggressive phenotypes by compromising the tumor suppressor activity of ER?, and hence, MTA1-ER? axis might serve a new therapeutic target for the salivary gland cancer. PMID:26168722

  17. 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

  18. Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ER??/? mice

    PubMed Central

    Fan, Xiaotang; Gabbi, Chiara; Kim, Hyun-Jin; Cheng, Guojun; Andersson, Leif C.; Warner, Margaret; Gustafsson, Jan-ke

    2010-01-01

    At 2 years of age, 100% (23/23) of ER??/? female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors developed in ER??/? mice or in ER???/? double knockout mice. The tumors have high proliferation indices, are ER?-positive, ER?-negative, and express high levels of nuclear phospho-SMAD3. Mice with granulosa cell tumors also had hyperproliferative endometria. The cause of the pituitary tumors appeared to be excessive secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus resulting from high expression of NPY. The ovarian phenotype is similar to that seen in mice where inhibin is ablated. The data indicate that ER? plays an important role in regulating GnRH secretion. We suggest that in the absence of ER?, the proliferative action of FSH/SMAD3 is unopposed and the high proliferation leads to the development of ovarian tumors. The absence of tumors in the ER???/? mice suggests that tumor development requires the presence of ER?. PMID:20308571

  19. Synthesis, crystal structure and electrical properties of A-site cation ordered BaErMn2O5 and BaErMn2O6

    NASA Astrophysics Data System (ADS)

    ?wierczek, Konrad; Klimkowicz, Alicja; Zheng, Kun; Dabrowski, Bogdan

    2013-07-01

    In this paper, we report on a synthesis procedure, structural and electrical properties of BaErMn2O5 and BaErMn2O6, A-site double perovskites having layered arrangement of Ba and Er cations. These materials belong to a family of BaLnMn2O5+? oxides, which up to now were successfully synthesized for Ln=Y and La-Ho lanthanides. Up to our knowledge, this is the first report on the successful synthesis of BaErMn2O5 and BaErMn2O6, yielding>95 wt% of the considered compounds. Structural characterization of the materials is given at room temperature, together with in situ XRD studies, performed during oxidation of BaErMn2O5 in air, at elevated temperatures up to 500 C. A complex structural behavior was observed, with oxidation process of BaErMn2O5 occurring at around 300 C. The oxidized BaErMn2O6 shows a structural phase transition at about 225 C. Results of structural studies are supported by thermogravimetric measurements of the oxidation process, performed in air, as well as reduction process, preformed in 5 vol% of H2 in Ar. Additionally, isothermal oxidation/reduction cycles were measured at 500 C, showing interesting properties of BaErMn2O5+?, from a point of view of oxygen storage technology. Electrical conductivity of BaErMn2O5 is of the order of 10-4 S cm-1 at room temperature and shows activated character on temperature with activation energy Ea=0.30(1) eV. Positive sign of Seebeck coefficient for this material indicates holes as dominant charge carriers. Oxidized BaErMn2O6 possesses much higher electrical conductivity, almost 0.2 S cm-1 at room temperature. Additional, about 10-fold increase of electrical conductivity, occurring in the vicinity of 225 C for this material, can be associated with phase transition from charge/orbital-ordered insulator COI(CE) to paramagnetic metal PM phase. The highest conductivity for BaErMn2O6 was measured near 500 C and is almost equal to 40 S cm-1, while negative sign of Seebeck coefficient can be associated with electrons being dominant charge carriers.

  20. 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.

  1. ?-AR Blockers Suppresses ER Stress in Cardiac Hypertrophy and Heart Failure

    PubMed Central

    Ni, Li; Zhou, Changqing; Duan, Quanlu; Lv, Jiagao; Fu, Xiangning; Xia, Yong; Wang, Dao Wen

    2011-01-01

    Background Long-term ?-adrenergic receptor (?-AR) blockade reduces mortality in patients with heart failure. Chronic sympathetic hyperactivity in heart failure causes sustained ?-AR activation, and this can deplete Ca2+ in endoplasmic reticulum (ER) leading to ER stress and subsequent apoptosis. We tested the effect of ?-AR blockers on ER stress pathway in experimental model of heart failure. Methods and discussions ER chaperones were markedly increased in failing hearts of patients with end-stage heart failure. In Sprague-Dawley rats, cardiac hypertrophy and heart failure was induced by abdominal aortic constriction or isoproterenol subcutaneous injection. Oral ?-AR blockers treatment was performed in therapy groups. Cardiac remodeling and left ventricular function were analyzed in rats failing hearts. After 4 or 8 weeks of banding, rats developed cardiac hypertrophy and failure. Cardiac expression of ER chaperones was significantly increased. Similar to the findings above, sustained isoproterenol infusion for 2 weeks induced cardiac hypertrophy and failure with increased ER chaperones and apoptosis in hearts. ?-AR blockers treatment markedly attenuated these pathological changes and reduced ER stress and apoptosis in failing hearts. On the other hand, ?-AR agonist isoproterenol induced ER stress and apoptosis in cultured cardiomyocytes. ?-AR blockers largely prevented ER stress and protected myocytes against apoptosis. And ?-AR blockade significantly suppressed the overactivation of CaMKII in isoproterenol-stimulated cardiomyocytes and failing hearts in rats. Conclusions Our results demonstrated that ER stress occurred in failing hearts and this could be reversed by ?-AR blockade. Alleviation of ER stress may be an important mechanism underlying the therapeutic effect of ?-AR blockers on heart failure. PMID:22073308

  2. Genetic variants of ApoE and ApoER2 differentially modulate endothelial function

    PubMed Central

    Ulrich, Victoria; Konaniah, Eddy S.; Herz, Joachim; Gerard, Robert D.; Jung, Eunjeong; Yuhanna, Ivan S.; Ahmed, Mohamed; Hui, David Y.; Mineo, Chieko; Shaul, Philip W.

    2014-01-01

    It is poorly understood why there is greater cardiovascular disease risk associated with the apolipoprotein E4 (apoE) allele vs. apoE3, and also greater risk with the LRP8/apolipoprotein E receptor 2 (ApoER2) variant ApoER2-R952Q. Little is known about the function of the apoEApoER2 tandem outside of the central nervous system. We now report that in endothelial cells apoE3 binding to ApoER2 stimulates endothelial NO synthase (eNOS) and endothelial cell migration, and it also attenuates monocyteendothelial cell adhesion. However, apoE4 does not stimulate eNOS or endothelial cell migration or dampen cell adhesion, and alternatively it selectively antagonizes apoE3/ApoER2 actions. The contrasting endothelial actions of apoE4 vs. apoE3 require the N-terminal to C-terminal interaction in apoE4 that distinguishes it structurally from apoE3. Reconstitution experiments further reveal that ApoER2-R952Q is a loss-of-function variant of the receptor in endothelium. Carotid artery reendothelialization is decreased in ApoER2?/? mice, and whereas adenoviral-driven apoE3 expression in wild-type mice has no effect, apoE4 impairs reendothelialization. Moreover, in a model of neointima formation invoked by carotid artery endothelial denudation, ApoER2?/? mice display exaggerated neointima development. Thus, the apoE3/ApoER2 tandem promotes endothelial NO production, endothelial repair, and endothelial anti-inflammatory properties, and it prevents neointima formation. In contrast, apoE4 and ApoER2-R952Q display dominant-negative action and loss of function, respectively. Thus, genetic variants of apoE and ApoER2 impact cardiovascular health by differentially modulating endothelial function. PMID:25197062

  3. ER? decreases breast cancer cell survival by regulating the IRE1/XBP-1 pathway.

    PubMed

    Rajapaksa, G; Nikolos, F; Bado, I; Clarke, R; Gustafsson, J-; Thomas, C

    2015-07-30

    Unfolded protein response (UPR) is an adaptive reaction that allows cancer cells to survive endoplasmic reticulum (EnR) stress that is often induced in the tumor microenvironment because of inadequate vascularization. Previous studies report an association between activation of the UPR and reduced sensitivity to antiestrogens and chemotherapeutics in estrogen receptor ? (ER?)-positive and triple-negative breast cancers, respectively. ER? has been shown to regulate the expression of a key mediator of the EnR stress response, the X-box-binding protein-1 (XBP-1). Although network prediction models have associated ER? with the EnR stress response, its role as regulator of the UPR has not been experimentally tested. Here, upregulation of wild-type ER? (ER?1) or treatment with ER? agonists enhanced apoptosis in breast cancer cells in the presence of pharmacological inducers of EnR stress. Targeting the BCL-2 to the EnR of the ER?1-expressing cells prevented the apoptosis induced by EnR stress but not by non-EnR stress apoptotic stimuli indicating that ER?1 promotes EnR stress-regulated apoptosis. Downregulation of inositol-requiring kinase 1? (IRE1?) and decreased splicing of XBP-1 were associated with the decreased survival of the EnR-stressed ER?1-expressing cells. ER?1 was found to repress the IRE1 pathway of the UPR by inducing degradation of IRE1?. These results suggest that the ability of ER?1 to target the UPR may offer alternative treatment strategies for breast cancer. PMID:25347741

  4. Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

    SciTech Connect

    Antonson, P.; Omoto, Y.; Humire, P.; Gustafsson, J.-A.; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204

    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 a 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.

  5. Microstructures and properties of superconducting Y-ErBaCuO thin films obtained from disordered Y-ErBaF2Cu films

    NASA Technical Reports Server (NTRS)

    Cikmach, P.; Diociaiuti, M.; Fontana, A.; Giovannella, C.; Iannuzzi, M.; Lucchini, C.; Merlo, V.; Messi, R.; Paoluzi, L.; Scopa, L.

    1991-01-01

    The preparation procedure used to obtain superconducting thin films by radio frequency magnetron sputtering of a single mosaic target is described in detail. The single mosaic target is composed of (Y-Er), BaF2, and Cu.

  6. Dysfunction of Endoplasmic Reticulum (ER) and Mitochondria (MT) in Alzheimer's Disease: The Role of the ER-MT Cross-Talk.

    PubMed

    Volgyi, Katalin; Juhsz, Gbor; Kovacs, Zsolt; Penke, Botond

    2015-01-01

    A common feature of neurodegenerative diseases is the formation of misfolded, mostly enzyme resistant proteins. These substances may form toxic assemblies according to the current concept of the neurodegenerative diseases. Overlapping of the misfolded proteins is typical in these disorders. The formation of misfolded proteins and toxic aggregates point to a common pathway of these disorders: failure in normal protein folding in the ER as a consequence of ER-stress and mitochondrial energy production. Alzheimer's disease (AD) is a rather heterogeneous, multifactorial disorder with wide clinical heterogeneity and is classified into several subtypes. In AD the processing of the amyloid precursor protein (APP) and formation of toxic ?-amyloid (A?) structures occur intraneuronally. A? affects both ER and mitochondria and disturbs Ca(2+)-homeostasis of the cells. Mitochondrial dysfunction is one of the main pathological events in AD. Mitochondria accumulate A? derived from the ER/Golgi or from the mitochondria-associated ER-membranes (MAM). Free radicals, oxidative stress and increasing Ca(2+)-concentration in mitochondria cause decreased ATP production. Mitochondrial dynamic and trafficking are also altered as a result of A? toxicity. Synaptic mitochondria show a very high vulnerability. Depletion of Ca(2+) level in the ER results in dysfunction of protein folding and evokes unfolded protein response (UPR), and affects also mitochondria. MAM may play special role in the ER-mitochondria cross talk. Mitochondria themselves (using mitochondria-targeting antioxidants such as MitoQ) could be a special target for AD treatment. Another targets are the UPR cascade proteins (PERK, IRE1, ATF6) and receptors involved in Ca(2+) -level stabilization of the ER (Ryr, IP3R). PMID:26159206

  7. Microstructures and properties of superconducting Y-Er-BaCu-O thin films obtained from disordered Y-Er-BaF2-Cu films

    NASA Technical Reports Server (NTRS)

    Cikmach, P.; Diociaiuti, M.; Fontana, A.; Giovannella, C.; Iannuzzi, M.; Lucchini, C.; Messi, R.; Paoluzi, L.; Scopa, L.; Tripodi, P.

    1990-01-01

    Since the first reports on superconducting thin films obtained by evaporating BaF2, Cu and Y(sup 1), or Yb or Er(sup 2), several others have followed. All these reports describe thin films prepared by means of molecular beam cells or electron guns. Researchers show that films with similar properties can be obtained by radio frequency sputtering of a single mosaic target composed by Y-Er, BaF2 and Cu. Process steps are described.

  8. Golgi-to-Endoplasmic Reticulum (ER) Retrograde Traffic in Yeast Requires Dsl1p, a Component of the ER Target Site that Interacts with a COPI Coat Subunit

    PubMed Central

    Reilly, Barbara A.; Kraynack, Bryan A.; VanRheenen, Susan M.; Waters, M. Gerard

    2001-01-01

    DSL1 was identified through its genetic interaction with SLY1, which encodes a t-SNARE-interacting protein that functions in endoplasmic reticulum (ER)-to-Golgi traffic. Conditional dsl1 mutants exhibit a block in ER-to-Golgi traffic at the restrictive temperature. Here, we show that dsl1 mutants are defective for retrograde Golgi-to-ER traffic, even under conditions where no anterograde transport block is evident. These results suggest that the primary function of Dsl1p may be in retrograde traffic, and that retrograde defects can lead to secondary defects in anterograde traffic. Dsl1p is an ER-localized peripheral membrane protein that can be extracted from the membrane in a multiprotein complex. Immunoisolation of the complex yielded Dsl1p and proteins of ?80 and ?55 kDa. The ?80-kDa protein has been identified as Tip20p, a protein that others have shown to exist in a tight complex with Sec20p, which is ?50 kDa. Both Sec20p and Tip20p function in retrograde Golgi-to-ER traffic, are ER-localized, and bind to the ER t-SNARE Ufe1p. These findings suggest that an ER-localized complex of Dsl1p, Sec20p, and Tip20p functions in retrograde traffic, perhaps upstream of a Sly1p/Ufe1p complex. Last, we show that Dsl1p interacts with the ?-subunit of the retrograde COPI coat, Ret2p, and discuss possible roles for this interaction. PMID:11739780

  9. Thermal lensing in Er, Yb : YVO4 crystal

    NASA Astrophysics Data System (ADS)

    Loiko, Pavel; Matrosov, Vladimir; Yumashev, Konstantin

    2015-03-01

    A thermal lens is characterized in 0.7 at.%Er, 3 at.%Yb : YVO4 yttrium vanadate crystal cut along the [1 0 0] crystallographic axis, for π and σ laser polarizations, by a probe beam method. For a pump spot radius of 100 μm and π-polarization, sensitivity factors of the thermal lens equal 5.7 and 7.9 m-1 W-1 (parallel and perpendicular to the [0 0 1]-axis, respectively); the astigmatism degree is 28%. The fractional heat load is determined by ISO-standard laser calorimetry, ηh = 0.63  ±  0.05. The anisotropy of the photo-elastic effect plays a dominant role in the formation of the astigmatic thermal lens.

  10. FINAL REPORT DOE/ER/63705-1

    SciTech Connect

    R.L. Street; F.L. Ludwig; Y. Chen

    2005-10-31

    Our DOE project is one of the efforts that comprised the Vertical Transport and Mixing Program [VTMX] of the Environmental Sciences Division of the Office of Biological and Environmental Research in Department of Energy and was supported originally by DOE grant ER 62847. The Advanced Regional Prediction System [ARPS] computer code was used to simulate flow in the Salt Lake Valley. The simulations provided evidence that atmospheric forcing interacts with the Jordan Narrows, the Traverse Range and other complex mountain terrain at the south end of the Salt Lake Valley to produce lee rotors, hydraulic jumps and other effects. This continuation grant was designed to allow us to complete our work on VTMX. The primary outcome of this grant was the completion of the dissertation of Dr. Ying Chen. In that work, several turbulence models were tested, a new surface vegetation model was developed, and Weather Research and Forecast code simulations were compared with ARPS runs.

  11. Excited state cross sections for Er-doped glasses

    NASA Astrophysics Data System (ADS)

    Zemon, Stanley A.; Lambert, Gary M.; Miniscalco, William J.; Davies, Richard W.; Hall, Bruce T.; Folweiler, Robert C.; Wei, Ta-Sheng; Andrews, Leonard J.; Singh, Mahendra P.

    1991-01-01

    Excited-state-absorption (ESA) cross sections were determined for the region between 760 and 900 nm for Er-doped fluorophosphate phosphate and silicate glasses. Measurements were performed on multimode fibers pumping at 647 nm with powers 1 . 5 Wto invert the population into the saturation regime. Over much of the 800-nm band ground-state-absorption (GSA) cross sections are equal to or greater than ESA cross sections. For comparison ESA was also measured for singlemode Al/P-doped silica fiber. The cross sections were incorporated into an amplifier model and the phosphate and fluorophosphate glasses were found to provide higher gain than silica for pumping in the 800-nm band. Photoexcited fluorozirconates were found to have substantial populations in the first four excited states and ESA transitions originating from these states are identified.

  12. Cirrus parameterization from the FIRE ER-2 observations

    NASA Technical Reports Server (NTRS)

    Spinhirne, James D.

    1990-01-01

    Primary goals for the FIRE field experiments were validation of satellite cloud retrievals and study of cloud radiation parameters. The radiometers and lidar observations which were acquired from the NASA ER-2 high altitude aircraft during the FIRE cirrus field study may be applied to derive quantities which would be applicable for comparison to satellite retrievals and to define the cirrus radiative characteristics. The analysis involves parameterization of the vertical cloud distribution and relative radiance effects. An initial case study from the 28 Oct. 1986 cirrus experiment has been carried out, and results from additional experiment days are to be reported. The observations reported are for 1 day. Analysis of the many other cirrus observation cases from the FIRE study show variability of results.

  13. Detection of Change in Supercycles in ER Ursae Majoris

    NASA Astrophysics Data System (ADS)

    Zemko, Polina; Kato, Taichi; Shugarov, Sergei Yu.

    2013-06-01

    We examined data from observations of ER UMa during a period of 20 years available in the AAVSO, VSNET, AFOEV, NSVS, and VSOLJ databases together with published light curves. The obtained O - C diagram revealed a systematic change of the supercycle (time interval between two successive superoutbursts) ranging from 43.6 to 59.2 d. The time-scale of this cycle variation is from 300 to 1900 d. The number of normal outbursts within the supercycles also varied between 4 and 6, although no strong correlation between this number and the supercycle length was found. We suggest that the appearance of negative superhumps is responsible for the observed variations in the number of normal outbursts. Our results generally confirm the expectations based on the thermal-tidal instability theory.

  14. Amalgam ablation with the Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

    1995-04-01

    Any laser that will be used by dentist to replace the dental drill (handpiece) must remove dental hard tissues safely. These lasers must also have the ability to ablate the restorative dental materials which are present in the teeth being treated. Prior to any laser being used to treat humans a thorough knowledge of the effects of the laser treatment on dental materials must be understood. Cores of dental amalgam were created and sliced into thin wafers for this experiment. Ablation efficiency and thermal changes were evaluated with and without water. It appears as if the Er:YAG laser can effectively ablate amalgam dental material with and without water. The water prevents the temperature from increasing much above baseline and does not reduce efficiency of ablation.

  15. Side diode pumped ultra-compact Er:glass laser

    NASA Astrophysics Data System (ADS)

    Vitkin, Vladimir V.; Polyakov, Vadim M.; Kharitonov, Artem A.; Buchenkov, Vyacheslav A.; Rodionov, Andrey Y.

    2015-07-01

    We demonstrate side pumped ultra-compact Q-switched Er:glass laser for rangefinding with 1.4 mJ energy at 1.54 um. Laser diode with 75 W power and 5 ms pulse duration was used. Active medium was enveloped with diffuse reflector. Output pulse energy in free-running mode was 27 mJ with a slope efficiency of 12%. Transparent glass-ceramics containing Co2+:MgAl2O4 nanocrystals were used as a passive gate to ensure Q-switching in an operation temperature range and transverse mode selection. The Q-switch mode had steady operation at 1 Hz repetition rate with thermal effects playing no visible role.

  16. Wideband multi-element Er-doped fiber amplifier

    NASA Astrophysics Data System (ADS)

    Thipparapu, N. K.; Jain, S.; May-Smith, T. C.; Sahu, J. K.

    2014-09-01

    A multi-element Er-doped fiber amplifier (MEEDFA) is demonstrated in which the gain profile is extended into the S and L bands. Each fiber element of the MEEDFA is found to provide a maximum gain of 37?dB and a noise figure of < 4?dB in the C-band. The gain profile of the amplifier is shifted towards longer wavelength by cascading fiber elements. The novel geometry of the multi-element fiber (MEF) could allow for the development of a broadband amplifier in a split-band configuration. The proposed amplifier can operate in the wavelength band of 1520 to 1595?nm (75?nm), with a minimum gain of 20?dB.

  17. PO*WW*ER mobile treatment unit process hazards analysis

    SciTech Connect

    Richardson, R.B.

    1996-06-01

    The objective of this report is to demonstrate that a thorough assessment of the risks associated with the operation of the Rust Geotech patented PO*WW*ER mobile treatment unit (MTU) has been performed and documented. The MTU was developed to treat aqueous mixed wastes at the US Department of Energy (DOE) Albuquerque Operations Office sites. The MTU uses evaporation to separate organics and water from radionuclides and solids, and catalytic oxidation to convert the hazardous into byproducts. This process hazards analysis evaluated a number of accident scenarios not directly related to the operation of the MTU, such as natural phenomena damage and mishandling of chemical containers. Worst case accident scenarios were further evaluated to determine the risk potential to the MTU and to workers, the public, and the environment. The overall risk to any group from operation of the MTU was determined to be very low; the MTU is classified as a Radiological Facility with low hazards.

  18. Ice discharge from north and northeast Greenland using ERS data

    NASA Technical Reports Server (NTRS)

    Rignot, Eric

    1997-01-01

    Ice discharge from north and northeast Greenland glaciers was calculated at the grounding line using ERS radar interferometry data acquired during the tandem phase. The resulting estimates exceed the production of icebergs at the glacier fronts by a factor of 3.5. This large decrease in ice flux is attributed to extensive melting at the underside of the floating sections. When compared to the predicted grounding line ice discharge of an ice sheet in balance, the results show an excess of 28 cubic km/yr of ice lost to the ocean. The north and northeast sectors of the Greenland ice sheet are therefore thinning and contributing positively to sea-level rise.

  19. Er:YAG laser for endodontics: efficiency and safety

    NASA Astrophysics Data System (ADS)

    Hibst, Raimund; Stock, Karl; Gall, Robert; Keller, Ulrich

    1997-12-01

    Recently it has been shown that bacterias can be sterilized by Er:YAG laser irradiation. By optical fiber transmission the bactericidal effect can also be used in endodontics. In order to explore potential laser parameters, we further investigated sterilization of caries and measured temperatures in models simulating endodontic treatment. It was found out that the bactericidal effect is cumulative, with single pulses being active. This offers to choose all laser parameters except pulse energy (radiant exposure) from technical, practical or safety considerations. For clinical studies the following parameter set is proposed for efficient and safe application (teeth with a root wall thickness > 1 mm, and prepared up to ISO 50): pulse energy: 50 mJ, repetition rate: 15 Hz, fiber withdrawal velocity: 2 mm/s. With these settings 4 passes must be performed to accumulate the total dose for sterilization.

  20. ER Stress Response in Human Cellular Models of Senescence.

    PubMed

    Matos, Liliana; Gouveia, Alexandra Monteiro; Almeida, Henrique

    2015-08-01

    The aging process is characterized by progressive accumulation of damaged biomolecules in the endoplasmic reticulum, as result of increased oxidative stress accompanying cellular senescence. In agreement, we hypothesized that WI-38 human cellular models of replicative senescence and stress-induced premature senescence (SIPS) induced by hydrogen peroxide (H2O2-SIPS) or copper sulfate (CuSO4-SIPS) would present endoplasmic reticulum chaperoning mechanisms impairment and unfolded protein response activation. Results show that in replicative senescence and CuSO4-SIPS, immunoglobulin binding protein, calnexin, protein disulfide isomerase, and ER oxireductin-1 levels adjust to restore proteostasis and inositol-requiring enzyme-1 (IRE1)-, activating transcription factor 6 (ATF6)-, and pancreatic ER kinase (PERK)-mediated unfolded protein response are activated. However, H2O2-SIPS does not exhibit IRE1 and ATF6 pathways activation but a PERK-mediated upregulation of CCAAT/enhancer-binding protein homologous protein, showing that CuSO4-SIPS mimics better the endoplasmic reticulum molecular events of replicative senescence than H2O2-SIPS. Moreover, unfolded protein response activation is required for both SIPS models induction, because PERK and IRE1 inhibitors decreased senescence-associated beta-galactosidase appearance. In CuSO4-SIPS, the decrease in senescence levels is associated with PERK-driven, but IRE1 independent, cell cycle arrest while in H2O2-SIPS cell proliferation is PERK independent. These results add a step further on the molecular mechanisms that regulate senescence induction; moreover, they validate CuSO4-SIPS model as a useful tool to study cellular stress responses during aging, hoping to postpone age-related health decline. PMID:25149687

  1. Completion Report for Well ER-18-2

    SciTech Connect

    Bechtel Nevada

    2003-09-01

    Well ER-18-2 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well, located on Buckboard Mesa in the western part of the Nevada Test Site, was drilled in the spring of 1999 as part of the U.S. Department of Energy's hydrogeologic investigation well program in the Western Pahute Mesa - Oasis Valley region just west of the Test Site. A 44.5-centimeter surface hole was drilled and cased off to the depth 408.1 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 762.0 meters. A preliminary composite, static, water level was measured at the depth of approximately 369.7 meters approximately two months after the completion string was installed. One completion string with three isolated, slotted intervals was installed in the well. Detailed lithologic descriptions with preliminary stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters and 15 sidewall samples taken at various depths below 420 meters, supplemented by geophysical log data and results of detailed chemical and mineralogical studies of rock samples. The upper part of the well penetrated Tertiary-age basalt, underlain by tuffaceous moat-filling sediments interbedded with ash-flow tuff units of the Thirsty Canyon Group and the Beatty Wash Formation. The lower half of the drill hole penetrated ash-flow tuff of the mafic-rich Ammonia Tanks Tuff. The geologic interpretation of data from Well ER-18-2 indicates that this site is located inside the structural margin of the Ammonia Tanks caldera.

  2. Completion Report for Well ER-EC-1

    SciTech Connect

    Townsend, M.J.

    2000-12-01

    Well ER-EC-1 was drilled for the U.S. Department of Energy, Nevada Operations Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well was drilled in the spring of 1999 as part of the U.S. Department of Energy's hydrogeologic investigation well program in the Western Pahute Mesa - Oasis Valley region just west of the Test Site. A 44.5-centimeter surface hole was drilled and cased off to the depth 675.1 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 1,524.0 meters. A preliminary composite, static, water level was measured at the depth of approximately 566.3 meters prior to installation of the completion string. One completion string with three isolated, slotted intervals was installed in the well. Detailed lithologic descriptions with preliminary stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters and 31 sidewall samples taken at various depths below 680 meters, supplemented by geophysical log data. Detailed chemical and mineralogical studies of rock samples are in progress. The well penetrated Tertiary-age lava and tuff of the Timber Mountain Group, the Paintbrush Group, the Calico Hills Formation, the Crater Flat Group, and the Volcanics of Quartz Mountain. The preliminary geologic interpretation of data from Well ER-EC-1 indicates the presence of a structural trough or bench filled with a thick section of post-Rainier Mesa lava. These data also suggest that this site is located on a buried structural ridge that may separate the Silent Canyon and Timber Mountain caldera complexes.

  3. Growth, Thermal and Spectral Properties of Er3+-Doped and Er3+/Yb3+-Codoped Li3Ba2La3(WO4)8 Crystals

    PubMed Central

    Xiao, Bin; Lin, Zhoubin; Zhang, Lizhen; Huang, Yisheng; Wang, Guofu

    2012-01-01

    This paper reports the growth and spectral properties of Er3+-doped and Er3+/Yb3+-codoped Li3Ba2La3(WO4)8 crystals. The Er3+: Li3Ba2La3(WO4)8 crystal with dimensions of 56 mm28 mm9 mm and Er3+/Yb3+: Li3Ba2La3(WO4)8 crystal with dimensions of 52 mm24 mm8 mm were obtained by the top-seeded solution growth (TSSG) method. Thermal expansion coefficients and thermal conductivity of both crystals were measured. The spectroscopic characterizations of both crystals were investigated. The spectroscopic analysis reveals that the Er3+/Yb3+: Li3Ba2La3(WO4)8 crystal has much better optical properties than the Er3+: Li3Ba2La3(WO4)8 crystal, thus it may become a potential candidate for solid-state laser gain medium material. PMID:22808214

  4. The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation

    PubMed Central

    Schwarz, Dianne S.

    2014-01-01

    How cells shape and remodel organelles in response to cellular signals is a poorly understood process. Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU. A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner. Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal. Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation. Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner. Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER. PMID:25287301

  5. 20 CFR 218.17 - When a remarried widow(er) annuity begins.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false When a remarried widow(er) annuity begins. 218.17 Section 218.17 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ANNUITY BEGINNING AND ENDING DATES When an Annuity Begins § 218.17 When a remarried widow(er) annuity begins. (a) A remarried...

  6. 7 CFR 1794.22 - Categorically excluded proposals requiring an ER.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the ER; (10) Construction of new water supply wells and associated pipelines not located within the... turbine with a rating of 200 MW or less on an existing combustion turbine generation site for the purpose... covered in the ER. (b) Water and waste program. For certain proposed actions, applications for...

  7. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Election of the RLS by a widow(er) or parent. 234.47 Section 234.47 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment 234.47 Election of the RLS by a widow(er)...

  8. A thrombospondin-dependent pathway for a protective ER stress response

    PubMed Central

    Lynch, Jeffrey M.; Maillet, Marjorie; Vanhoutte, Davy; Schloemer, Aryn; Sargent, Michelle A.; Blair, N. Scott; Lynch, Kaari A.; Okada, Tetsuya; Aronow, Bruce J.; Osinska, Hanna; Prywes, Ron; Lorenz, John N.; Mori, Kazutoshi; Lawler, Jack; Robbins, Jeffrey; Molkentin, Jeffery D.

    2012-01-01

    SUMMARY Thrombospondin (Thbs) proteins are induced in sites of tissue damage or active remodeling. The endoplasmic reticulum (ER) stress response is also prominently induced with disease where it regulates protein production and resolution of misfolded proteins. Here we describe a novel function for Thbs’ as ER resident effectors of an adaptive ER stress response. Thbs4 cardiac-specific transgenic mice were protected from myocardial injury while Thbs4−/− mice were sensitized to cardiac maladaptation. Thbs induction produced a unique profile of adaptive ER stress response factors and expansion of the ER and downstream vesicles. The type-3 repeat domain in Thbs’ bind the ER luminal domain of activating transcription factor 6α (Atf6α) to promote its nuclear shuttling. Thbs4−/−mice failed to show activation of Atf6α and other ER stress response factors with injury, and Thbs4-mediated protection was lost when Atf6α was deleted. Hence, Thbs’ can function inside the cell during disease/remodeling to augment ER function and protect through a mechanism involving regulation of Atf6α. PMID:22682248

  9. Survival of Er(a+) red cells in a patient with allo-anti-Era

    SciTech Connect

    Thompson, H.W.; Skradski, K.J.; Thoreson, J.R.; Polesky, H.F.

    1985-03-01

    /sup 51/Chromium-labeled Er(a+) red cells survived nearly normally (T1/2 of 21 days) in a patient with allo-anti-Era. Transfusion of Er(a+) blood was without significant reaction and did not affect the anti-Era titer.

  10. The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation.

    PubMed

    Schwarz, Dianne S; Blower, Michael D

    2014-10-13

    How cells shape and remodel organelles in response to cellular signals is a poorly understood process. Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU. A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner. Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal. Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation. Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner. Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER. PMID:25287301

  11. Lifetime imaging of a fluorescent protein sensor reveals surprising stability of ER thiol redox

    PubMed Central

    Cross, Benedict C.S.; Kaminski Schierle, Gabriele S.; Winters, Mikael; Harding, Heather P.; Melo, Eduardo Pinho; Kaminski, Clemens F.

    2013-01-01

    Interfering with disulfide bond formation impedes protein folding and promotes endoplasmic reticulum (ER) stress. Due to limitations in measurement techniques, the relationships of altered thiol redox and ER stress have been difficult to assess. We report that fluorescent lifetime measurements circumvented the crippling dimness of an ER-tuned fluorescent redox-responsive probe (roGFPiE), faithfully tracking the activity of the major ER-localized protein disulfide isomerase, PDI. In vivo lifetime imaging by time-correlated single-photon counting (TCSPC) recorded subtle changes in ER redox poise induced by exposure of mammalian cells to a reducing environment but revealed an unanticipated stability of redox to fluctuations in unfolded protein load. By contrast, TCSPC of roGFPiE uncovered a hitherto unsuspected reductive shift in the mammalian ER upon loss of luminal calcium, whether induced by pharmacological inhibition of calcium reuptake into the ER or by physiological activation of release channels. These findings recommend fluorescent lifetime imaging as a sensitive method to track ER redox homeostasis in mammalian cells. PMID:23589496

  12. 20 CFR 216.65 - Who is an employee's widow(er).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... months before the day the employee died; (b) Is the natural parent of the employee's child; (c) Was... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Who is an employee's widow(er). 216.65... Who is an employee's widow(er). An individual who was married to the employee at the employee's...

  13. 20 CFR 216.65 - Who is an employee's widow(er).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... months before the day the employee died; (b) Is the natural parent of the employee's child; (c) Was... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Who is an employee's widow(er). 216.65 Section... Who is an employee's widow(er). An individual who was married to the employee at the employee's...

  14. Configuration Analysis of the ERS Points in Large-Volume Metrology System

    PubMed Central

    Jin, Zhangjun; Yu, Cijun; Li, Jiangxiong; Ke, Yinglin

    2015-01-01

    In aircraft assembly, multiple laser trackers are used simultaneously to measure large-scale aircraft components. To combine the independent measurements, the transformation matrices between the laser trackers’ coordinate systems and the assembly coordinate system are calculated, by measuring the enhanced referring system (ERS) points. This article aims to understand the influence of the configuration of the ERS points that affect the transformation matrix errors, and then optimize the deployment of the ERS points to reduce the transformation matrix errors. To optimize the deployment of the ERS points, an explicit model is derived to estimate the transformation matrix errors. The estimation model is verified by the experiment implemented in the factory floor. Based on the proposed model, a group of sensitivity coefficients are derived to evaluate the quality of the configuration of the ERS points, and then several typical configurations of the ERS points are analyzed in detail with the sensitivity coefficients. Finally general guidance is established to instruct the deployment of the ERS points in the aspects of the layout, the volume size and the number of the ERS points, as well as the position and orientation of the assembly coordinate system. PMID:26402685

  15. Configuration Analysis of the ERS Points in Large-Volume Metrology System.

    PubMed

    Jin, Zhangjun; Yu, Cijun; Li, Jiangxiong; Ke, Yinglin

    2015-01-01

    In aircraft assembly, multiple laser trackers are used simultaneously to measure large-scale aircraft components. To combine the independent measurements, the transformation matrices between the laser trackers' coordinate systems and the assembly coordinate system are calculated, by measuring the enhanced referring system (ERS) points. This article aims to understand the influence of the configuration of the ERS points that affect the transformation matrix errors, and then optimize the deployment of the ERS points to reduce the transformation matrix errors. To optimize the deployment of the ERS points, an explicit model is derived to estimate the transformation matrix errors. The estimation model is verified by the experiment implemented in the factory floor. Based on the proposed model, a group of sensitivity coefficients are derived to evaluate the quality of the configuration of the ERS points, and then several typical configurations of the ERS points are analyzed in detail with the sensitivity coefficients. Finally general guidance is established to instruct the deployment of the ERS points in the aspects of the layout, the volume size and the number of the ERS points, as well as the position and orientation of the assembly coordinate system. PMID:26402685

  16. Converging pathways in the occurrence of endoplasmic reticulum (ER) stress in Huntington's disease.

    PubMed

    Vidal, R; Caballero, B; Couve, A; Hetz, C

    2011-02-01

    A variety of neurological diseases including Huntington's disease (HD), Alzheimer's disease and Parkinson's disease share common neuropathology, primarily featuring the presence of abnormal protein inclusions containing specific misfolded proteins. Mutations leading to expansion of a poly-glutamine track in Huntingtin cause HD, and trigger its misfolding and aggregation. Recent evidence indicates that alterations in the secretory pathway, in particular the endoplasmic reticulum (ER), are emerging features of HD. Although it is not clear how cytoplasmic/nuclear located mutant Huntingtin alters the function of the ER, several reports indicate that mutant Huntingtin affects many essential processes related to the secretory pathway, including inhibition of ER-associated degradation, altered ER/Golgi vesicular trafficking and axonal transport, disrupted autophagy and abnormal ER calcium homeostasis. All these alterations are predicted to have a common pathological outcome associated to disturbance of protein folding and maturation pathways at the ER, generating chronic ER stress and neuronal dysfunction. Here, we review recent evidence involving ER stress in HD pathogenesis and discuss possible therapeutic strategies to target organelle function in the context of disease. PMID:21189122

  17. A Hands-On Approach to Teaching Protein Translation & Translocation into the ER

    ERIC Educational Resources Information Center

    LaBonte, Michelle L.

    2013-01-01

    The process of protein translation and translocation into the endoplasmic reticulum (ER) can often be challenging for introductory college biology students to visualize. To help them understand how proteins become oriented in the ER membrane, I developed a hands-on activity in which students use Play-Doh to simulate the process of protein…

  18. Dietary soy phytoestrogens and ER? signalling modulate interferon gamma production in response to bacterial infection

    PubMed Central

    CURRAN, E M; JUDY, B M; NEWTON, L G; LUBAHN, D B; ROTTINGHAUS, G E; MACDONALD, R S; FRANKLIN, C; ESTES, D M

    2004-01-01

    Diets rich in soy phytoestrogens have many potential health benefits but isoflavones such as genistein may suppress cell mediated immune function. The effect of dietary phytoestrogens on the host response to infection has not been extensively examined. Mice were fed a diet containing soy phytoestrogens and infected with Mycobacterium avium to establish a chronic infection and inflammatory response. As phytoestrogens may act through classical oestrogen receptors (ER), mice deficient in ER? signalling and wild type mice were evaluated for a panel of Type 1-associated cytokines (IFN?, IL-12 and IL-18) in the spleen. IFN? production in the spleen was increased approximately 4-fold in ER?-deficient mice fed a casein-based diet over wild type mice fed a casein-based diet (P < 005), suggesting a role for ER? in suppressing IFN? production. IL-18 levels in spleens of wild type mice were decreased compared to ER?-deficient mice on a casein diet. Splenic IL-12 and IL-18 levels were not affected in wild type and ER?-deficient mice on the phytoestrogen containing diets, with the exception that whole soy increased IL-12 levels in the tissues of ER? deficient mice. We conclude that ER? and dietary phytoestrogens can influence production of key regulatory cytokines in response to chronic bacterial infection. PMID:14738448

  19. Thermal conductivity of near-stoichiometric (U, Er)O 2 solid solutions

    NASA Astrophysics Data System (ADS)

    Kim, Si-Hyung; Kim, Yeon-Gu; Kim, Han-Soo; Na, Sang-Ho; Lee, Young-Woo; Suhr, Dong-Soo

    2005-06-01

    Thermal diffusivities of UO 2 and UO 2 doped with 1, 3, 5, 7 and 10 mol % ErO 1.5 were measured in the range of 298-1673 K by a laser flash method and their thermal conductivities were calculated from the thermal diffusivity, the measured sample density and published specific heat capacity data. The temperature dependence of the thermal conductivity up to 1673 K in UO 2 and UO 2-doped with ErO 1.5 was found to be modeled well using the phonon conduction equation, K = ( A + BT) -1. The thermal conductivities of the UO 2 and (U, Er)O 2 solid solutions gradually decreased with the temperature. The thermal conductivity of the doped UO 2 decreased relative to UO 2 with an increase of ErO 1.5 content at low temperatures, while it was independent of the ErO 1.5 content at higher temperatures. The variation of parameters A and B as a function of ErO 1.5 content is found experimentally and it is found that the dependence of the thermal conductivity of (U, Er)O 2 on temperature up to 1673 K and on the ErO 1.5 content can be expressed as K={K}/{1+K(kAy+kByT)}.

  20. A Hands-On Approach to Teaching Protein Translation & Translocation into the ER

    ERIC Educational Resources Information Center

    LaBonte, Michelle L.

    2013-01-01

    The process of protein translation and translocation into the endoplasmic reticulum (ER) can often be challenging for introductory college biology students to visualize. To help them understand how proteins become oriented in the ER membrane, I developed a hands-on activity in which students use Play-Doh to simulate the process of protein

  1. Diacylglycerol Kinase δ Suppresses ER-to-Golgi Traffic via Its SAM and PH Domains

    PubMed Central

    Nagaya, Hisao; Wada, Ikuo; Jia, Yan-Jun; Kanoh, Hideo

    2002-01-01

    We report here that the anterograde transport from the endoplasmic reticulum (ER) to the Golgi was markedly suppressed by diacylglycerol kinase δ (DGKδ) that uniquely possesses a pleckstrin homology (PH) and a sterile α motif (SAM) domain. A low-level expression of DGKδ in NIH3T3 cells caused redistribution into the ER of the marker proteins of the Golgi membranes and the vesicular-tubular clusters (VTCs). In this case DGKδ delayed the ER-to-Golgi traffic of vesicular stomatitis virus glycoprotein (VSV G) and also the reassembly of the Golgi apparatus after brefeldin A (BFA) treatment and washout. DGKδ was demonstrated to associate with the ER through its C-terminal SAM domain acting as an ER-targeting motif. Both of the SAM domain and the N-terminal PH domain of DGKδ were needed to exert its effects on ER-to-Golgi traffic. Kinase-dead mutants of DGKδ were also effective as the wild-type enzyme, suggesting that the catalytic activity of DGK was not involved in the present observation. Remarkably, the expression of DGKδ abrogated formation of COPII-coated structures labeled with Sec13p without affecting COPI structures. These findings indicate that DGKδ negatively regulates ER-to-Golgi traffic by selectively inhibiting the formation of ER export sites without significantly affecting retrograde transport. PMID:11809841

  2. Upconversion-pumped IR (2.8-2.9 microns) lasing of Er3+ in garnets

    NASA Astrophysics Data System (ADS)

    Pollack, S. A.; Chang, David B.; Birnbaum, Milton; Kokta, Milan R.

    1991-07-01

    Optical properties and upconversion-pumped lasing on the 4I11/2 4I13/2 transition of the Er3+ ion were studied in two garnet crystals, (33% Er) Y3Al5O12 and (25%) Y3Sc2Ga3O12. The (Er) YSGG crystal was grown at Union Carbide. Absorption and emission spectra of the crystals were studied at 300K, 77K and 4K. Stark-splittings were determined from the 4K absorption spectra for the five lowest excited states. Fluorescence lifetimes for several excited states were measured at 300K and 77K using 355 nm 10 ns Q-switch pulses of tripled Nd:YAG; and 1.53 micrometers pulses of an Er:glass laser. In the latter case, fluorescence was excited via ion-pair upconversion. In (Er)YAG at 300K under UV excitation, the lifetime of the 4I13/2 state is almost two orders of magnitude longer than the lifetime of the 4I13/2 in Er:YSGG. The lifetime of the 4I13/2 state is only a factor of 5 longer than the 4I11/2 state. The upconversion lasing characteristics of Er:YSGG and Er:YAG are described and related to the measured spectral and lifetime measurements.

  3. High temperature cavity polaritons in epitaxial Er2O3 on silicon

    NASA Astrophysics Data System (ADS)

    Michael, C. P.; Sabnis, V. A.; Yuen, H. B.; Jamora, A.; Semans, S.; Atanackovic, P. B.; Painter, O.

    2009-03-01

    Cavity polaritons around two Er3+ optical transitions are observed in microdisk resonators fabricated from epitaxial Er2O3 on Si(111). Using a pump-probe method, spectral anticrossings and linewidth averaging of the polariton modes are measured in the cavity transmission and luminescence at temperatures above 361 K.

  4. PREDICTING ER BINDING AFFINITY FOR EDC RANKING AND PRIORITIZATION: MODEL II

    EPA Science Inventory

    The training set used to derive a common reactivity pattern (COREPA) model for estrogen receptor (ER) binding affinity in Model I (see Abstract I in this series) was extended to include 47 rat estrogen receptor (rER) relative binding affinity (RBA) measurements in addition to the...

  5. Efficient energy transfer from Si clusters to Er3+ in complex silicate glasses

    NASA Astrophysics Data System (ADS)

    Lebour, Y.; Pellegrino, P.; Garca, C.; Moreno, J. A.; Garrido, B.

    2006-10-01

    We present an extensive study of the structural and optical emission properties in aluminum silicates and soda-lime silicates codoped with Si nanoclusters (Si-nc) and Er. Si excess of 5 and 15at.% and Er concentrations ranging from 21019 up to 61020cm-3 were introduced by ion implantation. Thermal treatments at different temperatures were carried out before and after Er implantation. Structural characterization of the resulting structures was performed to obtain the layer composition and the size distribution of Si clusters. A comprehensive study has been carried out of the light emission as a function of the matrix characteristics, Si and Er contents, excitation wavelength, and power. Er emission at 1540nm has been detected in all coimplanted glasses, with similar intensities. We estimated lifetimes ranging from 2.5to12ms (depending on the Er dose and Si excess) and an effective excitation cross section of about 110-17cm2 at low fluxes that decreases at high pump power. By quantifying the amount of Er ions excited through Si-nc we find a fraction of 10% of the total Er concentration. Upconversion coefficients of about 310-18cm-3s-1 have been found for soda-lime glasses and one order of magnitude lower in aluminum

  6. Are entangled particles connected by wormholes? Evidence for the ER =EPR conjecture from entropy inequalities

    NASA Astrophysics Data System (ADS)

    Gharibyan, Hrant; Penna, Robert F.

    2014-03-01

    If spacetime is built out of quantum bits, does the shape of space depend on how the bits are entangled? The ER =EPR conjecture relates the entanglement entropy of a collection of black holes to the cross sectional area of Einstein-Rosen (ER) bridges (or wormholes) connecting them. We show that the geometrical entropy of classical ER bridges satisfies the subadditivity, triangle, strong subadditivity, and Cadney-Linden-Winter inequalities. These are nontrivial properties of entanglement entropy, so this is evidence for ER =EPR. We further show that the entanglement entropy associated with classical ER bridges has nonpositive tripartite information. This is not a property of entanglement entropy, in general. For example, the entangled four qubit pure state |GHZ4?=(|0000?+|1111?)/?2 has positive tripartite information, so this state cannot be described by a classical ER bridge. Large black holes with massive amounts of entanglement between them can fail to have a classical ER bridge if they are built out of |GHZ4? states. States with nonpositive tripartite information are called monogamous. We conclude that classical ER bridges require monogamous EPR correlations.

  7. Influence of Bi on the Er luminescence in yttrium-erbium disilicate thin films

    SciTech Connect

    Scarangella, Adriana; Miritello, Maria; Priolo, Francesco

    2014-09-28

    The influence of bismuth on erbium optical properties at 1.54 ?m has been investigated in yttrium-erbium disilicate thin films synthesized by magnetron co-sputtering and implanted with two Bi different doses. The Bi depth distribution and the evolution of its oxidation states after annealing treatments at 1000 C in two atmospheres, O? and N?, have been investigated. It was found that only in O? the Bi? valence state is prevalent, thanks to the enhanced Bi mobility in the oxidizing ambient, as demonstrated by Rutherford backscattering spectrometry. At lower Bi content, although the formation of Bi? metallic nanoparticles that are deleterious non radiative channels for Er luminescence, efficient energy transfer from Bi to Er has been obtained only in O?. It is due to the excitation of ultraviolet broad Bi?? absorption band and the energy transfer to Er ions. We have evaluated that in this case, Er effective excitation cross section increased by a factor of 5 in respect with the one for direct Er absorption at 488 nm. At higher Bi dose, this mechanism is absent, but an increased Er optical efficiency at 1.54 ?m has been observed under resonant excitation. It is due to the contribution of a fraction of Er ions having an increased lifetime. This phenomenon is associated with the formation of Bi agglomerates, induced at higher Bi doses, which well isolate Er from non-radiative quenching centers. The increased decay time assures higher optical efficiency at 1.54 ?m.

  8. Synthetic Marijuana Lands Thousands of Young People in the ER, Especially Young Males

    MedlinePLUS

    ... People in the ER, Especially Young Males Synthetic Marijuana Lands Thousands of Young People in the ER, ... on the scene a few years ago, synthetic marijuana (MJ)—often called “Spice” or “K2”—has become ...

  9. When to Go to the ER if Your Child Has Asthma

    MedlinePLUS

    ... When to Go to the ER if Your Child Has Asthma KidsHealth > For Parents > When to Go to the ER if Your Child Has Asthma Print A A A Text Size ... you discuss it with your doctor before your child has a severe flare-up. The doctor's instructions ...

  10. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... regulations, as defined in ER 1110-2-241, 33 CFR part 208. (4) Monthly water control charts (RCS DAEN-CWE-6... included in the post flood reports required by ER 500-1-1, 33 CFR part 203. (n) Water Control Management... of projects, but including flood control and navigation regulation of projects subject to 33 CFR...

  11. Stress sensing in plants by an ER stress sensor/transducer, bZIP28

    PubMed Central

    Srivastava, Renu; Deng, Yan; Howell, Stephen H.

    2014-01-01

    Two classes of ER stress sensors are known in plants, membrane-associated basic leucine zipper (bZIP) transcription factors and RNA splicing factors. ER stress occurs under adverse environmental conditions and results from the accumulation of misfolded or unfolded proteins in the ER lumen. One of the membrane-associated transcription factors activated by heat and ER stress agents is bZIP28. In its inactive form, bZIP28 is a type II membrane protein with a single pass transmembrane domain, residing in the ER. bZIP28’s N-terminus, containing a transcriptional activation domain, is oriented towards the cytoplasm and its C-terminal tail is inserted into the ER lumen. In response to stress, bZIP28 exits the ER and moves to the Golgi where it is proteolytically processed, liberating its cytosolic component which relocates to the nucleus to upregulate stress-response genes. bZIP28 is thought to sense stress through its interaction with the major ER chaperone, binding immunoglobulin protein (BIP). Under unstressed conditions, BIP binds to intrinsically disordered regions in bZIP28’s lumen-facing tail and retains it in the ER. A truncated form of bZIP28, without its C-terminal tail is not retained in the ER but migrates constitutively to the nucleus. Upon stress, BIP releases bZIP28 allowing it to exit the ER. One model to account for the release of bZIP28 by BIP is that BIP is competed away from bZIP28 by the accumulation of misfolded proteins in the ER. However, other forces such as changes in energy charge levels, redox conditions or interaction with DNAJ proteins may also promote release of bZIP28 from BIP. Movement of bZIP28 from the ER to the Golgi is assisted by the interaction of elements of the COPII machinery with the cytoplasmic domain of bZIP28. Thus, the mobilization of bZIP28 in response to stress involves the dissociation of factors that retain it in the ER and the association of factors that mediate its further organelle-to-organelle movement. PMID:24616727

  12. Novel intronic promoter in the rat ER alpha gene responsible for the transient transcription of a variant receptor.

    PubMed

    Tiffoche, C; Vaillant, C; Schausi, D; Thieulant, M L

    2001-09-01

    To analyze the molecular origin of an ER variant, the truncated ER product-1, transiently expressed at the proestrus in lactotrope cells, we generated a 2.5-kb sequence of a genomic region upstream and downstream the specific sequence truncated ER product-1. Genomic Southern blot analysis showed that truncated ER product-1 is spliced from a noncoding leader exon localized within the intron 4 of the ER alpha gene. Analysis of the promoter sequence revealed the presence of a major transcriptional start site, a canonical TATA box and putative cis regulatory elements for pituitary specific expression as well as an E-responsive element. In transient transfection, the truncated ER product-1 promoter was transcriptionally the most active in the lactotrope cell lines (MMQ). Analysis of truncated ER product-1 functionality showed that: 1) the protein inhibited ER alpha binding to the E-responsive element in electromobility shift assays, 2) inhibited the E2 binding to ER alpha in binding assays, 3) the truncated ER product-1/ER alpha complex antagonized the transcriptional activity elicited by E2, 4) nuclear localization of green fluorescent protein-ER alpha was altered in Chinese hamster ovary cell lines stably expressing truncated ER product-1. Collectively, these data demonstrated that the protein exerts full dominant negative activity against ER alpha. Moreover, truncated ER product-1/ER alpha complex also repressed the activity of all promoters tested to date, suggesting a general inhibitory effect toward transcription. In conclusion, the data suggest that truncated ER product-1 could regulate estrogen signaling via a specific promoter in lactotrope cells. PMID:11517190

  13. ER contact sites define the position and timing of endosome fission

    PubMed Central

    Rowland, Ashley A.; Chitwood, Patrick J.; Phillips, Melissa J.; Voeltz, Gia K.

    2014-01-01

    Summary Endocytic cargo and Rab GTPases are segregated to distinct domains of an endosome. These domains maintain their identity until they undergo fission to traffic cargo. It is not fully understood how segregation of cargo or Rab proteins is maintained along the continuous endosomal membrane, or what machinery is required for fission. Endosomes form contact sites with the ER that are maintained during trafficking. Here, we show that stable contacts form between the ER and endosome at constricted sorting domains and that free diffusion of cargo is limited at these positions. We demonstrate that the site of constriction and fission for early and late endosomes is spatially and temporally linked to contact sites with the ER. Lastly, we show that altering ER structure and dynamics reduces the efficiency of endosome fission. Together these data reveal a surprising role for ER contact in defining the timing and position of endosome fission. PMID:25416943

  14. Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance.

    PubMed

    Contreras, Cristina; Gonzlez-Garca, Ismael; Martnez-Snchez, Noelia; Seoane-Collazo, Patricia; Jacas, Jordi; Morgan, Donald A; Serra, Dolors; Gallego, Rosala; Gonzalez, Francisco; Casals, Nria; Nogueiras, Rubn; Rahmouni, Kamal; Diguez, Carlos; Lpez, Miguel

    2014-10-01

    Hypothalamic endoplasmic reticulum (ER) stress is a key mechanism leading to obesity. Here, we demonstrate that ceramides induce lipotoxicity and hypothalamic ER stress, leading to sympathetic inhibition, reduced brown adipose tissue (BAT) thermogenesis, and weight gain. Genetic overexpression of the chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) in the ventromedial nucleus of the hypothalamus (VMH) abolishes ceramide action by reducing hypothalamic ER stress and increasing BAT thermogenesis, which leads to weight loss and improved glucose homeostasis. The pathophysiological relevance of this mechanism is demonstrated in obese Zucker rats, which show increased hypothalamic ceramide levels and ER stress. Overexpression of GRP78 in the VMH of these animals reduced body weight by increasing BAT thermogenesis as well as decreasing leptin and insulin resistance and hepatic steatosis. Overall, these data identify a triangulated signaling network involving central ceramides, hypothalamic lipotoxicity/ER stress, and BAT thermogenesis as a pathophysiological mechanism of obesity. PMID:25284795

  15. Reversal of ER-? silencing by chromatin modifying agents overrides acquired tamoxifen resistance.

    PubMed

    Pitta, Chara A; Papageorgis, Panagiotis; Charalambous, Christiana; Constantinou, Andreas I

    2013-09-01

    The purpose of this work is to determine the molecular mechanisms underlying tamoxifen resistance. We show here that ER-? is epigenetically silenced in a cell line with acquired tamoxifen resistance (MCF-7/TAM-R) and this could be reversed by 5-AZA-deoxycytidine (5-AZA) and trichostatin-A (TSA) pre-treatment. Subsequent treatment with 4-hydroxy-tamoxifen (4-OHT) induced ER-? nuclear translocation, upregulated pS2 and p21 levels and reduced cell viability. Transfection with an ER-? expression vector sensitized MCF-7/TAM-R cells to the growth inhibitory and pro-apoptotic effects of 4-OHT, indicating that ER-? re-expression alone is sufficient to restore sensitivity to tamoxifen. This novel finding reveals that ER-? is fundamental in overcoming acquired tamoxifen resistance and provides insights for new therapeutic protocols against breast cancer. PMID:23752064

  16. Magnetocrystalline anisotropy of Er2(Fe1 - x V x )17 compounds

    NASA Astrophysics Data System (ADS)

    Terentev, P. B.; Mushnikov, N. V.; Gerasimov, E. G.; Gaviko, V. S.; Stashkova, L. A.

    2015-08-01

    The magnetic properties and magnetic anisotropy of the Er2(Fe1- x V x )17 compounds (with x = 0-0.05) have been studied. The Curie temperature ( T C) of the compounds has been found to increase as the vanadium concentration increases. It has been shown that the Er2(Fe1 - x V x )17 compounds have the easy-plane anisotropy in the temperature range from, 77 K to T C. Magnetization curves have been measured and the temperature dependences of the K 1 and K 2 anisotropy constants have been calculated. Contributions from the Er and Fe magnetic sublattices to the magnetic anisotropy constants were distinguished. An analysis of the obtained data allowed us to conclude that the cause for the existence of first-order magnetization processes in Er2Fe17 at low temperatures is a positive contribution from the Er sublattice to K 1 and a negative contribution from it to K 2.

  17. Synthesis and characterization of Er:Yb3Al5O12 nanopowder

    NASA Astrophysics Data System (ADS)

    Li, Chun; Xu, Jialin; Liu, Wang; Lin, Hai; Liu, Yu; Wang, Dan; Zhai, Jian; Fu, Tiehan; Zhou, Hu; Li, Yusheng; Liu, Jinghe; Zeng, Fanming

    2015-12-01

    Er:Yb1Al5O12 (Er:YbAG) nanopowder was prepared by carbonate coprecipitation method. Highpurity Er:YbAG powder was obtained after calcination at as low as 1000°C with an average particle size of 70 nm. The Al-O-Yb phonon vibrations were investigated and the absorption band arisen from interaction between lattice vibration and photon in YbAG is located around 610 cm-1. A strong emission peak of powder was observed at 1.53 µm with 980 nm laser excitation. An energy transfer mechanism between Yb3+ and Er3+ states responsible for the peak emission was proposed. An optimum Er3+ dopant concentration was determined.

  18. Carrier transfer from InAs quantum dots to ErAs metal nanoparticles

    SciTech Connect

    Haughn, C. R.; Chen, E. Y.; Zide, J. M. O.; Doty, M. F.; Steenbergen, E. H.; Bissell, L. J.; Eyink, K. G.

    2014-09-08

    Erbium arsenide (ErAs) is a semi-metallic material that self-assembles into nanoparticles when grown in GaAs via molecular beam epitaxy. We use steady-state and time-resolved photoluminescence to examine the mechanism of carrier transfer between indium arsenide (InAs) quantum dots and ErAs nanoparticles in a GaAs host. We probe the electronic structure of the ErAs metal nanoparticles (MNPs) and the optoelectronic properties of the nanocomposite and show that the carrier transfer rates are independent of pump intensity. This result suggests that the ErAs MNPs have a continuous density of states and effectively act as traps. The absence of a temperature dependence tells us that carrier transfer from the InAs quantum dots to ErAs MNPs is not phonon assisted. We show that the measured photoluminescence decay rates are consistent with a carrier tunneling model.

  19. Photoluminescence of Er-doped silicon nanoparticles from sputtered SiO x thin films

    NASA Astrophysics Data System (ADS)

    Biggemann, Daniel; Mustafa, Danilo; Tessler, Leandro R.

    2006-05-01

    We present a study of the Er 3+ photoluminescence from Er-doped thin SiO x films prepared by reactive RF sputtering from a silicon target partially covered by metallic erbium platelets in an Ar + O 2 atmosphere. Annealing at 1250 C induces the formation of silicon nanocrystals and modifies the Er 3+ luminescence spectrum due to changes in the Er 3+ environment. The photoluminescence efficiency decreases by two orders of magnitude with nanoparticle formation. This decrease may be due to less efficient energy transfer processes from the nanocrystals than from the amorphous matrix, to the formation of more centro-symmetric Er 3+ sites at the nanocrystal surfaces or to very different optimal erbium concentrations between amorphous and crystallized samples.

  20. The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection

    PubMed Central

    Fung, To Sing; Torres, Jaume; Liu, Ding Xiang

    2015-01-01

    Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved self-eating mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed. PMID:26053926

  1. Structural, electronic and magnetic properties of Er implanted ZnO thin films

    NASA Astrophysics Data System (ADS)

    Murmu, P. P.; Kennedy, J.; Ruck, B. J.; Leveneur, J.

    2015-09-01

    We report the structural, electronic and magnetic properties of Er implanted and annealed ZnO thin films. The effect of annealing in oxygen-deficient and oxygen-rich conditions was investigated. Rutherford backscattering spectrometry results revealed that the Er atoms are located at the implantation depth of around 13 nm, and annealing conditions had no adverse effect on the Er concentration in the layer. Raman spectroscopy results showed peak related to E2(high) mode of ZnO indicating enhanced crystalline quality of the Er implanted and annealed ZnO films. X-ray absorption near edge spectroscopy results demonstrated pre-edge features in O K-edge which are attributed to the structural defects in the films. Room temperature magnetic ordering was observed in Er implanted and annealed films, and is mainly assigned to the intrinsic defects in ZnO.

  2. Enhancement of Er optical efficiency through bismuth sensitization in yttrium oxide

    NASA Astrophysics Data System (ADS)

    Scarangella, Adriana; Reitano, Riccardo; Franzò, Giorgia; Priolo, Francesco; Miritello, Maria

    2015-07-01

    The process of energy transfer (ET) between optically active ions has been widely studied to improve the optical efficiency of a system for different applications, from lighting and photovoltaics to silicon microphotonics. In this work, we report the influence of Bi on the Er optical emission in erbium-yttrium oxide thin films synthesized by magnetron co-sputtering. We demonstrate that this host permits to well dissolve Er and Bi ions, avoiding their clustering, and thus to stabilize the optically active Er3+ and Bi3+ valence states. In addition, we establish the ET occurrence from Bi3+ to Er3+ by the observed Bi3+ PL emission decrease and the simultaneous Er3+ photoluminescence (PL) emission increase. This was further confirmed by the coincidence of the Er3+ and Bi3+ excitation bands, analyzed by PL excitation spectroscopy. By increasing the Bi content of two orders of magnitude inside the host, though the occurrence of Bi-Bi interactions becomes deleterious for Bi3+ optical efficiency, the ET process between Bi3+ and Er3+ is still prevalent. We estimate ET efficiency of 70% for the optimized Bi:Er ratio equal to 1:3. Moreover, we have demonstrated to enhance the Er3+ effective excitation cross section by more than three orders of magnitude with respect to the direct one, estimating a value of 5.3 × 10-18 cm2, similar to the expected Bi3+ excitation cross section. This value is one of the highest obtained for Er in Si compatible hosts. These results make this material very promising as an efficient emitter for Si-compatible photonics devices.

  3. The aggregation-prone intracellular serpin SRP-2 fails to transit the ER in Caenorhabditis elegans.

    PubMed

    Silverman, Richard M; Cummings, Erin E; O'Reilly, Linda P; Miedel, Mark T; Silverman, Gary A; Luke, Cliff J; Perlmutter, David H; Pak, Stephen C

    2015-05-01

    Familial encephalopathy with neuroserpin inclusions bodies (FENIB) is a serpinopathy that induces a rare form of presenile dementia. Neuroserpin contains a classical signal peptide and like all extracellular serine proteinase inhibitors (serpins) is secreted via the endoplasmic reticulum (ER)-Golgi pathway. The disease phenotype is due to gain-of-function missense mutations that cause neuroserpin to misfold and aggregate within the ER. In a previous study, nematodes expressing a homologous mutation in the endogenous Caenorhabditis elegans serpin, srp-2, were reported to model the ER proteotoxicity induced by an allele of mutant neuroserpin. Our results suggest that SRP-2 lacks a classical N-terminal signal peptide and is a member of the intracellular serpin family. Using confocal imaging and an ER colocalization marker, we confirmed that GFP-tagged wild-type SRP-2 localized to the cytosol and not the ER. Similarly, the aggregation-prone SRP-2 mutant formed intracellular inclusions that localized to the cytosol. Interestingly, wild-type SRP-2, targeted to the ER by fusion to a cleavable N-terminal signal peptide, failed to be secreted and accumulated within the ER lumen. This ER retention phenotype is typical of other obligate intracellular serpins forced to translocate across the ER membrane. Neuroserpin is a secreted protein that inhibits trypsin-like proteinase. SRP-2 is a cytosolic serpin that inhibits lysosomal cysteine peptidases. We concluded that SRP-2 is neither an ortholog nor a functional homolog of neuroserpin. Furthermore, animals expressing an aggregation-prone mutation in SRP-2 do not model the ER proteotoxicity associated with FENIB. PMID:25786854

  4. Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress

    PubMed Central

    Xu, S; Nam, S M; Kim, J-H; Das, R; Choi, S-K; Nguyen, T T; Quan, X; Choi, S J; Chung, C H; Lee, E Y; Lee, I-K; Wiederkehr, A; Wollheim, C B; Cha, S-K; Park, K-S

    2015-01-01

    Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca2+ increase due to depletion of luminal ER Ca2+. Palmitate-induced ER Ca2+ depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca2+ pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca2+ depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca2+ loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca2+ depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA leads to mitochondrial dysfunction and ER Ca2+ depletion through FAT/CD36 and PLC signaling, possibly contributing to podocyte injury. PMID:26583319

  5. AR collaborates with ER? in aromatase inhibitor-resistant breast cancer.

    PubMed

    Rechoum, Yassine; Rovito, Daniela; Iacopetta, Domenico; Barone, Ines; And, Sebastiano; Weigel, Nancy L; O'Malley, Bert W; Brown, Powel H; Fuqua, Suzanne A W

    2014-10-01

    Androgen receptor (AR) is an attractive target in breast cancer because of its frequent expression in all the molecular subtypes, especially in estrogen receptor (ER)-positive luminal breast cancers. We have previously shown a role for AR overexpression in tamoxifen resistance. We engineered ER-positive MCF-7 cells to overexpress aromatase and AR (MCF-7 AR Arom cells) to explore the role of AR in aromatase inhibitor (AI) resistance. Androstendione (AD) was used as a substrate for aromatization to estrogen. The nonsteroidal AI anastrazole (Ana) inhibited AD-stimulated growth and ER transcriptional activity in MCF-7 Arom cells, but not in MCF-7 AR Arom cells. Enhanced activation of pIGF-1R and pAKT was found in AR-overexpressing cells, and their inhibitors restored sensitivity to Ana, suggesting that these pathways represent escape survival mechanisms. Sensitivity to Ana was restored with AR antagonists, or the antiestrogen fulvestrant. These results suggest that both AR and ER? must be blocked to restore sensitivity to hormonal therapies in AR-overexpressing ER?-positive breast cancers. AR contributed to ER? transcriptional activity in MCF-7 AR Arom cells, and AR and ER? co-localized in AD+Ana-treated cells, suggesting cooperation between the two receptors. AR-mediated resistance was associated with a failure to block ER transcriptional activity and enhanced up-regulation of AR and ER-responsive gene expression. Clinically, it may be necessary to block both AR and ER? in patients whose tumors express elevated levels of AR. In addition, inhibitors to the AKT/IGF-1R signaling pathways may provide alternative approaches to block escape pathways and restore hormone sensitivity in resistant breast tumors. PMID:25178514

  6. Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress.

    PubMed

    Xu, S; Nam, S M; Kim, J-H; Das, R; Choi, S-K; Nguyen, T T; Quan, X; Choi, S J; Chung, C H; Lee, E Y; Lee, I-K; Wiederkehr, A; Wollheim, C B; Cha, S-K; Park, K-S

    2015-01-01

    Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca(2+) increase due to depletion of luminal ER Ca(2+). Palmitate-induced ER Ca(2+) depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca(2+) pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca(2+) depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca(2+) loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca(2+) depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA leads to mitochondrial dysfunction and ER Ca(2+) depletion through FAT/CD36 and PLC signaling, possibly contributing to podocyte injury. PMID:26583319

  7. Spectroscopic properties and energy transfer in Er-Tm co-doped bismuth silicate glass

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Li, Zhilan; Li, Kefeng; Zhang, Lei; Cheng, Jimeng; Hu, Lili

    2013-10-01

    In this paper, we investigate the spectroscopic properties of and energy transfer processes in Er-Tm co-doped bismuth silicate glass. The Judd-Ofelt parameters of Er3+ and Tm3+ are calculated, and the similar values indicate that the local environments of these two kinds of rare earth ions are almost the same. When the samples are pumped at 980 nm, the emission intensity ratio of Tm:3F4 ? 3H6 to Er:4I13/2 ? 4I15/2 increases with increased Er3+ and Tm3+ contents, indicating energy transfer from Er:4I13/2 to Tm:3F4. When the samples are pumped at 800 nm, the emission intensity ratio of Er:4I13/2 ? 4I15/2 to Tm:3H4 ? 3F4 increases with increased Tm2O3 concentration, indicating energy transfer from Tm:3H4 to Er:4I13/2. The rate equations are given to explain the variations. The microscopic and macroscopic energy transfer parameters are calculated, and the values of energy transfer from Er:4I13/2 to Tm:3F4 are found to be higher than those of the other processes. For the Tm singly-doped glass pumped at 800 nm and Er-Tm co-doped glass pumped at 980 nm, the pumping rate needed to realize population reversion is calculated. The result shows that when the Er2O3 doping level is high, pumping the co-doped glass by a 980 nm laser is an effective way of obtaining a low-threshold 2 ?m gain.

  8. ER-α36, a Variant of ER-α, Promotes Tamoxifen Agonist Action in Endometrial Cancer Cells via the MAPK/ERK and PI3K/Akt Pathways

    PubMed Central

    Lin, Sheng-Li; Yan, Li-Ying; Zhang, Xin-Tian; Yuan, Ju; Li, Mo; Qiao, Jie; Wang, Zhao-Yi; Sun, Qing-Yuan

    2010-01-01

    Background Recently, a novel variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathways mediated by ER-α36 in tamoxifen resistance and agonist action. Methodology The cellular localization of ER-α36 was examined by immunofluorescence in MCF-7 cells and Hec1A cells. MCF-7 breast cancer cells, MCF-7 cells expressing recombinant ER-α36 (MCF-7/ER36), Hec1A endometrial cancer cells and Hec1A cells with siRNA knockdown of ER-α36 (Hec1A/RNAiER36) were treated with 17β-estradial (E2) and tamoxifen (TAM) in the absence and presence of kinase inhibitor U0126 and LY294002. We examined phosphorylation of signaling molecules and the expression of c-Myc by immunoblotting, and tumor cell growth by MTT assay. Conclusions ER variant ER-α36 enhances TAM agonist activity through activation of the membrane-initiated signaling pathways in endometrial cancer, and that ER-α36 is involved in de novo and acquired TAM resistance in breast cancer. PMID:20126312

  9. Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

    PubMed Central

    Irsigler, Andr ST; Costa, Maximiller DL; Zhang, Ping; Reis, Pedro AB; Dewey, Ralph E; Boston, Rebecca S; Fontes, Elizabeth PB

    2007-01-01

    Background Despite the potential of the endoplasmic reticulum (ER) stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP) from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress) or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5%) of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD) domain-containing proteins, an ubiquitin-associated (UBA) protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as downstream targets were inversely regulated by osmotic stress. Conclusion The present ER-stress- and osmotic-stress-induced transcriptional studies demonstrate a clear predominance of stimulus-specific positive changes over shared responses on soybean leaves. This scenario indicates that polyethylene glycol (PEG)-induced cellular dehydration and ER stress elicited very different up-regulated responses within a 10-h stress treatment regime. In addition to identifying ER-stress and osmotic-stress-specific responses in soybean (Glycine max), our global expression-profiling analyses provided a list of candidate regulatory components, which may integrate the osmotic-stress and ER-stress signaling pathways in plants. PMID:18036212

  10. Measurement of thermal neutron cross section and resonance integral for the 170Er(n, ?)171Er reaction by using a gold monitor

    NASA Astrophysics Data System (ADS)

    Nguyen, Van Do; Pham Duc, Khue; Kim Tien, Thanh; Nguyen Thi, Hien; Kim, Guinyun; Yang, Sungchul; Kim, Kyung Sook; Shin, Sung Gyun; Cho, Moo-Hyun; Lee, Man Woo

    2013-09-01

    The thermal neutron cross section (?0) and the resonance integral (I0) of the reaction 170Er(n, ?)171Er were measured by an activation method using a reaction 197Au(n, ?)198Au as a single comparator. The high-purity natural erbium (natEr) and gold (197Au) foils with and without Cd cover with the thickness of 0.5 mm were irradiated in a neutron field of the Pohang neutron facility. The induced activities in the activated foils were measured with a well calibrated coaxial HPGe detector. The thermal neutron cross section for the 170Er(n, ?)171Er reaction has been determined to be ?0 = 7.80 0.35 barn, relative to the reference value of 98.65 0.09 barn for the 197Au(n, ?)198Au reaction. By assuming the cadmium cut-off energy of 0.55 eV, the resonance integral for the 170Er(n, ?)171Er reaction is I0 = 40.4 2.8 barn, which is determined relative to the reference value of 1550 28 barn for the 197Au(n, ?)198Au reaction. In order to improve the accuracy of the experimental results the epithermal neutron spectrum shape factor (?) was determined, and the necessary corrections for the counting loss caused by ?-ray attenuation (Fg), the thermal neutron shelf-shielding (Gth), the resonance neutron self-shielding (Gepi) effects, the ?-ray coincidence summing effect, as well as neutron flux fluctuation. The present results are compared with the reference data and discussed.

  11. Structure, optical properties and thermal stability of HfErO films deposited by simultaneous RF and VHF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Zhang, H. Y.; He, H. J.; Zhang, Z.; Jin, C. G.; Yang, Y.; Wang, Y. Y.; Zhuge, L. J.; Ye, C.; Wu, X. M.

    2015-05-01

    HfErO films are deposited on Si substrates by simultaneous radio frequency (RF) and very high frequency (VHF) magnetron sputtering technique. The content of the doped ingredient of Er and the body composition of HfO x are, respectively, controlled through the VHF and RF powers. Low content of Er doping in the HfErO films can be achieved, because the VHF source of 27.12 MHz has higher ion energy and lower ion flux than the RF source resulting in low sputtering rate in the magnetron sputtering system. The structure, optical properties and thermal stability of the HfErO films are investigated in this work. Results show that the doped content of Er is independently controlled by the VHF power. The oxygen vacancies are created by the Er incorporation. The hafnium in the HfErO films forms mixed valence of Hf2+ and Hf4+. The HfErO films are composed with the structures of HfO2, HfO and ErO x , which can be optimized through the VHF power. At high VHF power, the Hf-Er-O bonds are formed, which demonstrates that the Er atoms are doped into the lattice of HfO2 in the HfErO films. The HfErO films have bad thermal stability as the crystallization temperature decreases from 900 to 800 °C. After thermal annealing, cubic phase of HfO2 are stabilized, which is ascribed to the oxygen vacancies creation by the Er incorporation. The optical properties such as the refractive index and the optical band gap of the HfErO films are optimized by the VHF power.

  12. Inhibitory role of ER? on anterior pituitary cell proliferation by controlling the expression of proteins related to cell cycle progression.

    PubMed

    Prez, Pablo A; Petiti, Juan P; Wagner, Ignacio A; Sabatino, Maria E; Sasso, Corina V; De Paul, Ana L; Torres, Alicia I; Gutirrez, Silvina

    2015-11-01

    Considering that the role of ER? in the growth of pituitary cells is not well known, the aim of this work was to determine the expression of ER? in normal and tumoral cells and to investigate its implications in the proliferative control of this endocrine gland, by analyzing the participation of cyclin D1, Cdk4 and p21. Our results showed that the expression of ER? decreased during pituitary tumoral development induced by chronic E2 stimulation. The 20 1.6% of normal adenohypophyseal cells expressed ER?, with this protein being reduced in the hyperplastic/adenomatous pituitary: at 20 days the ER?+ population was 10.7 2.2%, while after 40 and 60 days of treatment an almost complete loss in the ER? expression was observed (40 d: 1 0.6%; 60 d: 2 0.6%). The ER?/? ratio increased starting from tumors at 40 days, mainly due to the loss of ER? expression. The cell proliferation was analyzed in normal and hyperplastic pituitary and also in GH3?- and GH3?+ which contained different levels of ER? expression, and therefore different ER?/? ratios. The over-expression of ER? inhibited the GH3 cell proliferation and expression of cyclin D1 and ER?. Also, the ER? activation by its agonist DPN changed the subcellular localization of p21, inducing an increase in the p21 nuclear expression, where it acts as a tumoral suppressor. These results show that ER? exerts an inhibitory role on pituitary cell proliferation, and that this effect may be partially due to the modulation of some key regulators of the cell cycle, such as cyclin D1 and p21. These data contribute significantly to the understanding of the ER effects in the proliferative control of pituitary gland, specifically related to the ER? function in the E2 actions on this endocrine gland. PMID:26282612

  13. Antecedent wetness conditions based on ERS scatterometer data

    NASA Astrophysics Data System (ADS)

    Brocca, L.; Melone, F.; Moramarco, T.; Morbidelli, R.

    2009-01-01

    SummarySoil moisture is widely recognized as a key parameter in environmental processes mainly for the role of rainfall partitioning into runoff and infiltration. Therefore, for storm rainfall-runoff modeling the estimation of the antecedent wetness conditions ( AWC) is one of the most important aspect. In this context, this study investigates the potential of scatterometer on board of the ERS satellites for the assessment of wetness conditions in three Tiber sub-catchments (Central Italy), of which one includes an experimental area for soil moisture monitoring. The satellite soil moisture data are taken from the ERS/METOP soil moisture archive. First, the scatterometer-derived soil wetness index ( SWI) data are compared with two on-site soil moisture data sets acquired by different methodologies on areas of different extension ranging from 0.01 km 2 to ˜60 km 2. Moreover, the reliability of SWI to estimate the AWC at a catchment scale is investigated considering the relationship between SWI and the soil potential maximum retention parameter, S, of the Soil Conservation Service-Curve Number (SCS-CN) method for abstraction. Several flood events occurred from 1992 to 2005 are selected for this purpose. Specifically, the performance of the SWI for S estimation is compared with two antecedent precipitation indices ( API) and one base flow index ( BFI). The S values obtained through the observed direct runoff volume and rainfall depth are used as benchmark. Results show the great reliability of the SWI for the estimation of wetness conditions both at the plot and catchment scale despite the complex orography of the investigated areas. As far as the comparison with on site soil moisture data set is concerned, the SWI is found quite reliable in representing the soil moisture at layer depth of 15 cm, with a mean correlation coefficient equal to 0.81. The characteristic time length parameter variations, as expected, is depended on soil type, with values in accordance with previous studies. In terms of AWC assessment at catchment scale, based on selected flood events, the SWI is found highly correlated with the observed maximum potential retention of the SCS-CN method with a correlation coefficient R equal to -0.90. Besides, SWI in representing the AWC of the three investigated catchments, outperformed both API indices, poorly representative of AWC, and BFI. Finally, the classical SCS-CN method applied for direct runoff depth estimation, where S is assessed by SWI, provided good performance with a percentage error not exceeding ˜25% for 80% of investigated rainfall-runoff events.

  14. Oxytocin selectively increases ER? mRNA in the neonatal hypothalamus and hippocampus of female prairie voles

    PubMed Central

    Pournajafi-Nazarloo, Hossein; Carr, Michael S.; Papademeteriou, Eros; Schmidt, Jennifer V.; Cushing, Bruce S.

    2009-01-01

    During neonatal development exogenous oxytocin increases ER? immunoreactivity in the hypothalamus of female prairie voles. The purpose of this study was to determine if the increase in ER? is associated with an increase in ER? mRNA expression and to determine if the effect is specific to ER subtype or if oxytocin also influences ER? mRNA expression. On the day of birth female prairie vole pups were treated with oxytocin, an oxytocin antagonist, or saline. Brains were collected and RT-PCR was used to determine the effect of treatment on ER mRNA production in the hypothalamus, hippocampus, and cortex. Within 2 hours of treatment oxytocin significantly increased ER? mRNA expression in the hypothalamus and hippocampus, but not the cortex, while inhibiting the effects of endogenous oxytocin reduced the expression of ER? mRNA in the hippocampus. Neonatal treatment did not affect the expression of ER? mRNA. The results demonstrate that the effects of oxytocin treatment are region and ER subtype specific and that during the neonatal period oxytocin can affect the expression of ER? by altering message production. The regional specific changes in ER? mRNA expression in females are consistent with studies examining the behavioral and physiological effects of neonatal manipulation of oxytocin in females. PMID:17107710

  15. Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics

    PubMed Central

    Jaipargas, Erica-Ashley; Barton, Kiah A.; Mathur, Neeta; Mathur, Jaideep

    2015-01-01

    Mitochondria are pleomorphic, double membrane-bound organelles involved in cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are typically tubular-reticulate structures and several micro-meters long but in green plants they are predominantly observed as 0.2–1.5 μm punctae. While fission and fusion, through the coordinated activity of several conserved proteins, shapes mitochondria, the endoplasmic reticulum (ER) has recently been identified as an additional player in this process in yeast and mammalian cells. The mitochondria-ER relationship in plant cells remains largely uncharacterized. Here, through live-imaging of the entire range of mitochondria pleomorphy we uncover the underlying basis for the predominantly punctate mitochondrial form in plants. We demonstrate that mitochondrial morphology changes in response to light and cytosolic sugar levels in an ER mediated manner. Whereas, large ER polygons and low dynamics under dark conditions favor mitochondrial fusion and elongation, small ER polygons result in increased fission and predominantly small mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion to produce giant mitochondria. By observing elongated mitochondria in normal plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also establish that thin extensions called matrixules and a beads-on-a-string mitochondrial phenotype are direct consequences of mitochondria-ER interactions. PMID:26442089

  16. Ion beam synthesis of undoped and Er-doped Si nanocrystals

    NASA Astrophysics Data System (ADS)

    Franzò, G.; Moreira, E. C.; Pacifici, D.; Priolo, F.; Iacona, F.; Spinella, C.

    2001-04-01

    Our recent work on the ion beam synthesis of Si nanocrystals (nc) and Er-doped Si nc is presented. We will show that ion beam processing is a quite powerful way to obtain Si nc embedded within SiO 2. These nc have average sizes, photoluminescence (PL) peak position and PL time-decay curves dependent on the annealing temperature. In particular, with increasing annealing temperatures they become larger, with a red-shifted PL and with longer lifetimes (denoting a reduction in non-radiative processes and the presence of more isolated nc). When doped with Er ions the energy is preferentially transferred from the nc to the Er, with Er luminescence intensities orders of magnitude above those of Er-doped SiO 2. This is demonstrated to be due to an enhanced excitation cross-section for the Er ions caused by the sensitizer action of the nc. Finally, the insertion of Er-doped Si nc within an optical microcavity will be shown to produce a further luminescence enhancement.

  17. Optical activity and defect/dopant evolution in ZnO implanted with Er

    NASA Astrophysics Data System (ADS)

    Azarov, Alexander; Galeckas, Augustinas; Halln, Anders; Kuznetsov, Andrej; Monakhov, Edouard; Svensson, Bengt G.

    2015-09-01

    The effects of annealing on the optical properties and defect/dopant evolution in wurtzite (0001) ZnO single crystals implanted with Er ions are studied using a combination of Rutherford backscattering/channeling spectrometry and photoluminescence measurements. The results suggest a lattice recovery behavior dependent on ion dose and involving formation/evolution of an anomalous multipeak defect distribution, thermal stability of optically active Er complexes, and Er outdiffusion. An intermediate defect band occurring between the surface and ion-induced defects in the bulk is stable up to 900 C and has a photoluminescence signature around 420 nm well corresponding to Zn interstitials. The optical activity of the Er atoms reaches a maximum after annealing at 700 C but is not directly associated to the ideal Zn site configuration, since the Er substitutional fraction is maximal already in the as-implanted state. In its turn, annealing at temperatures above 700 C leads to dissociation of the optically active Er complexes with subsequent outdiffusion of Er accompanied by the efficient lattice recovery.

  18. Influence of doping concentration on microstructure evolution and sintering kinetics of Er:YAG transparent ceramics

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Liu, Qiang; Li, Jiang; Ivanov, Maxim; Ba, Xuewei; Yuan, Yong; Lin, Li; Chen, Min; Liu, Wenbin; Kou, Huamin; Shi, Yun; Chen, Haohong; Pan, Yubai; Cheng, Xiaonong; Guo, Jingkun

    2014-11-01

    Erbium doped yttrium aluminum garnet (Er:YAG) transparent ceramics with different Er doping concentrations were fabricated from powder mixtures of ?-Al2O3, Y2O3, and Er2O3 with tetraethoxysilane (TEOS) and MgO as sintering aids by solid-state reactive sintering. The sintering temperatures were from 1500 C up to 1750 C. Densification, microstructure evolution and optical transparency of Er:YAG ceramics with different doping concentrations were examined. For all the doping concentration, fully dense Er:YAG transparent ceramics with homogeneous grain size distributions around 20-23 ?m were obtained by sintering at 1750 C for 50 h, whose transmittances were all above 83% at the wavelength of 1200 nm. The grain growth kinetic of Er:YAG ceramics was also investigated as a function of erbium content. The calculated activation energies for grain growth of the 0.5, 1.0, 5.0, and 10 at%Er:YAG ceramics were 779, 855, 805, and 861 kJ/mol, respectively. The luminescence spectra were also measured and discussed.

  19. Multiple Domains in PEX16 Mediate Its Trafficking and Recruitment of Peroxisomal Proteins to the ER.

    PubMed

    Hua, Rong; Gidda, Satinder K; Aranovich, Alexander; Mullen, Robert T; Kim, Peter K

    2015-08-01

    Peroxisomes rely on a diverse array of mechanisms to ensure the specific targeting of their protein constituents. Peroxisomal membrane proteins (PMPs), for instance, are targeted by at least two distinct pathways: directly to peroxisomes from their sites of synthesis in the cytosol or indirectly via the endoplasmic reticulum (ER). However, the extent to which each PMP targeting pathway is involved in the maintenance of pre-existing peroxisomes is unclear. Recently, we showed that human PEX16 plays a critical role in the ER-dependent targeting of PMPs by mediating the recruitment of two other PMPs, PEX3 and PMP34, to the ER. Here, we extend these results by carrying out a comprehensive mutational analysis of PEX16 aimed at gaining insights into the molecular targeting signals responsible for its ER-to-peroxisome trafficking and the domain(s) involved in PMP recruitment function at the ER. We also show that the recruitment of PMPs to the ER by PEX16 is conserved in plants. The implications of these results in terms of the function of PEX16 and the role of the ER in peroxisome maintenance in general are discussed. PMID:25903784

  20. Intracellular lactate-mediated induction of estrogen receptor beta (ER?) in biphasic malignant pleural mesothelioma cells.

    PubMed

    Manente, Arcangela G; Pinton, Giulia; Zonca, Sara; Cilli, Michele; Rinaldi, Maurizio; Daga, Antonio; Nilsson, Stefan; Moro, Laura

    2015-09-22

    Biphasic malignant pleural mesothelioma (MPM) is the second most common histotype of MPM. It is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter associated with worse prognosis. In this report we describe that silencing of AKT1 in spindle-shaped biphasic MPM cells promotes the shift toward an epithelioid phenotype. Furthermore, AKT1 silencing resulted in decreased expression of the lactate/H+ symporter MCT4 and its chaperone CD147/Basigin, and in the induction of estrogen receptor ? (ER?) expression. We provide evidence that ER? expression is induced by increased intracellular lactate concentration. Spheroid culturing and tumor growth of ER? negative biphasic MPM in nude mice resulted in the induction of ER? expression and response to the selective agonist KB9520. In both models, the treatment with the ER? agonist results in reduced cell proliferation, decreased expression of MCT4 and CD147/Basigin and increased acetylation and inactivation of AKT1. Collectively, in response to metabolic changes, ER? expression is induced and exerts an anti-tumor effect through selective agonist activation. The possibility to reverse the more aggressive biphasic mesothelioma histotype by targeting ER? with a selective agonist could represent a new effective treatment strategy. PMID:26208479

  1. Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis

    PubMed Central

    Genereux, Joseph C; Qu, Song; Zhou, Minghai; Ryno, Lisa M; Wang, Shiyu; Shoulders, Matthew D; Kaufman, Randal J; Lasmzas, Corinne I; Kelly, Jeffery W; Wiseman, R Luke

    2015-01-01

    The Unfolded Protein Response (UPR) indirectly regulates extracellular proteostasis through transcriptional remodeling of endoplasmic reticulum (ER) proteostasis pathways. This remodeling attenuates secretion of misfolded, aggregation-prone proteins during ER stress. Through these activities, the UPR has a critical role in preventing the extracellular protein aggregation associated with numerous human diseases. Here, we demonstrate that UPR activation also directly influences extracellular proteostasis through the upregulation and secretion of the ER HSP40 ERdj3/DNAJB11. Secreted ERdj3 binds misfolded proteins in the extracellular space, substoichiometrically inhibits protein aggregation, and attenuates proteotoxicity of disease-associated toxic prion protein. Moreover, ERdj3 can co-secrete with destabilized, aggregation-prone proteins in a stable complex under conditions where ER chaperoning capacity is overwhelmed, preemptively providing extracellular chaperoning of proteotoxic misfolded proteins that evade ER quality control. This regulated co-secretion of ERdj3 with misfolded clients directly links ER and extracellular proteostasis during conditions of ER stress. ERdj3 is, to our knowledge, the first metazoan chaperone whose secretion into the extracellular space is regulated by the UPR, revealing a new mechanism by which UPR activation regulates extracellular proteostasis. PMID:25361606

  2. Highly Efficient Near-IR Photoluminescence of Er3+ Immobilized in Mesoporous SBA-15

    PubMed Central

    2010-01-01

    SiO2 mesoporous molecular sieve SBA-15 with the incorporation of erbium ions is studied as a novel type of nanoscopic composite photoluminescent material in this paper. To enhance the photoluminescence efficiency, two schemes have been used for the incorporation of Er3+ where (1) Er3+ is ligated with bis-(perfluoromethylsulfonyl)-aminate (PMS) forming Er(PMS)x-SBA-15 and (2) Yb3+ is codoped with Er3+ forming Yb-Er-SBA-15. As high as 11.17 × 10−21cm2 of fluorescent cross section at 1534 nm and 88 nm of “effective bandwidth” have been gained. It is a 29.3% boost in fluorescent cross section compared to what has been obtained in conventional silica. The upconversion coefficient in Yb-Er-SBA-15 is relatively small compared to that in other ordinary glass hosts. The increased fluorescent cross section and lowered upconversion coefficient could benefit for the high-gain optical amplifier. Finally, the Judd–Ofelt theory has also been used for the analyses of the optical spectra of Er(PMS)x-SBA-15. PMID:21170408

  3. Sec16 influences transitional ER sites by regulating rather than organizing COPII

    PubMed Central

    Bharucha, Nike; Liu, Yang; Papanikou, Effrosyni; McMahon, Conor; Esaki, Masatoshi; Jeffrey, Philip D.; Hughson, Frederick M.; Glick, Benjamin S.

    2013-01-01

    During the budding of coat protein complex II (COPII) vesicles from transitional endoplasmic reticulum (tER) sites, Sec16 has been proposed to play two distinct roles: negatively regulating COPII turnover and organizing COPII assembly at tER sites. We tested these ideas using the yeast Pichia pastoris. Redistribution of Sec16 to the cytosol accelerates tER dynamics, supporting a negative regulatory role for Sec16. To evaluate a possible COPII organization role, we dissected the functional regions of Sec16. The central conserved domain, which had been implicated in coordinating COPII assembly, is actually dispensable for normal tER structure. An upstream conserved region (UCR) localizes Sec16 to tER sites. The UCR binds COPII components, and removal of COPII from tER sites also removes Sec16, indicating that COPII recruits Sec16 rather than the other way around. We propose that Sec16 does not in fact organize COPII. Instead, regulation of COPII turnover can account for the influence of Sec16 on tER sites. PMID:24006484

  4. Effect of Er:YAG laser energy on the morphology of enamel/adhesive system interface

    NASA Astrophysics Data System (ADS)

    Delfino, Carina Sinclér; Souza-Zaroni, Wanessa Christine; Corona, Silmara Aparecida Milori; Pécora, Jesus Djalma; Palma-Dibb, Regina Guenka

    2006-10-01

    The aim of this study was to evaluate in vitro the influence of Er:YAG laser energy variation to cavity preparation on the morphology of enamel/adhesive system interface, using SEM. Eighteen molars were used and the buccal surfaces were flattened without dentine exposure. The specimens were randomly assigned to two groups, according to the adhesive system (conventional total-etching or self-etching), and each group was divided into three subgroups (bur carbide in turbine of high rotation, Er:YAG laser 250 mJ/4 Hz and Er:YAG laser 300 mJ/4 Hz) containing six teeth each. The enamel/adhesive system interface was serially sectioned and prepared for SEM. The Er:YAG laser, in general, produced a more irregular adhesive interface than the control group. For Er:YAG laser 250 mJ there was formation of a more regular hybrid layer with good tag formation, mainly in the total-etching system. However, Er:YAG laser 300 mJ showed a more irregular interface with amorphous enamel and fused areas, for both adhesive systems. It was concluded that cavity preparation with Er:YAG laser influenced on the morphology of enamel/adhesive system interface and the tissual alterations were more evident when the energy was increased.

  5. PEX16 contributes to peroxisome maintenance by constantly trafficking PEX3 via the ER.

    PubMed

    Aranovich, Alexander; Hua, Rong; Rutenberg, Andrew D; Kim, Peter K

    2014-09-01

    The endoplasmic reticulum (ER) is required for the de novo biogenesis of peroxisomes in mammalian cells. However, its role in peroxisome maintenance is unclear. To explore ER involvement in the maintenance of peroxisomes, we redirect a peroxisomal membrane protein (PMP), PEX3, to directly target to the ER using the N-terminal ER signal sequence from preprolactin. Using biochemical techniques and fluorescent imaging, we find that ER-targeting PEX3 (ssPEX3) is continuously imported into pre-existing peroxisomes. This suggests that the ER constitutively provides membrane proteins and associated lipids to pre-existing peroxisomes. Using quantitative time-lapse live-cell fluorescence microscopy applied to cells that were either depleted of or exogenously expressing PEX16, we find that PEX16 mediates the peroxisomal trafficking of two distinct peroxisomal membrane proteins, PEX3 and PMP34, via the ER. These results not only provide insight into peroxisome maintenance and PMP trafficking in mammalian cells but also highlight important similarities and differences in the mechanisms of PMP import between the mammalian and yeast systems. PMID:25002403

  6. WNT16-expressing Acute Lymphoblastic Leukemia Cells are Sensitive to Autophagy Inhibitors after ER Stress Induction

    PubMed Central

    Verras, Meletios; Papandreou, Ioanna; Denko, Nicholas C.

    2016-01-01

    Background Previous work from our group showed hypoxia can induce endoplasmic reticulum (ER) stress and block the processing of the WNT3 protein in cells engineered to express WNT3a. Acute lymphoblastic leukemia (ALL) cells with the t(1:19) translocation express the WNT16 gene, which is thought to contribute to transformation. Results ER-stress blocks processing of endogenous WNT16 protein in RCH-ACV and 697 ALL cells. Biochemical analysis showed an aggregation of WNT16 proteins in the ER of stressed cells. These large protein masses cannot be completely cleared by ER-associated protein degradation, and require for additional autophagic responses. Pharmacological block of autophagy significantly increased cell death in ER-stressed ALL. Furthermore, murine cells engineered to express WNT16 are similarly sensitized. Conclusion ALL cells expressing WNT16 are sensitive to ER stress, and show enhanced killing after addition of chloroquine. These findings suggest a potential clinical application of inducers of ER stress with inhibitors of autophagy in patients with high-risk ALL. PMID:26254351

  7. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+) and Negative (ER-) Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

    PubMed Central

    Semaan, Suzan M.; Wang, Xu; Marshall, Alan G.; Sang, Qing-Xiang Amy

    2012-01-01

    Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+) tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER-) tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining) and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples. PMID:22773931

  8. Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

    PubMed Central

    Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

    2013-01-01

    Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca2+ indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca2+ indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca2+ indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca2+ indicator and a hydrophilic fluorescent dye/Ca2+ complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0. PMID:23685703

  9. PBX1 genomic pioneer function drives ER? signaling underlying progression in breast cancer.

    PubMed

    Magnani, Luca; Ballantyne, Elizabeth B; Zhang, Xiaoyang; Lupien, Mathieu

    2011-11-01

    Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ER?) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ER?-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ER? in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells through ChIP-seq and FAIRE-seq reveals that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. Accordingly, PBX1 guides ER? recruitment to a specific subset of sites. Expression profiling studies demonstrate that PBX1 controls over 70% of the estrogen response. More importantly, the PBX1-dependent transcriptional program is associated with poor-outcome in breast cancer patients. Correspondingly, PBX1 expression alone can discriminate a priori the outcome in ER?-positive breast cancer patients. These features are markedly different from the previously characterized ER?-associated pioneer factor FoxA1. Indeed, PBX1 is the only pioneer factor identified to date that discriminates outcome such as metastasis in ER?-positive breast cancer patients. Together our results reveal that PBX1 is a novel pioneer factor defining aggressive ER?-positive breast tumors, as it guides ER? genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression. PMID:22125492

  10. Emergence of Chaotic Scattering in Ultracold Er and Dy

    NASA Astrophysics Data System (ADS)

    Maier, T.; Kadau, H.; Schmitt, M.; Wenzel, M.; Ferrier-Barbut, I.; Pfau, T.; Frisch, A.; Baier, S.; Aikawa, K.; Chomaz, L.; Mark, M. J.; Ferlaino, F.; Makrides, C.; Tiesinga, E.; Petrov, A.; Kotochigova, S.

    2015-10-01

    We show that for ultracold magnetic lanthanide atoms chaotic scattering emerges due to a combination of anisotropic interaction potentials and Zeeman coupling under an external magnetic field. This scattering is studied in a collaborative experimental and theoretical effort for both dysprosium and erbium. We present extensive atom-loss measurements of their dense magnetic Feshbach-resonance spectra, analyze their statistical properties, and compare to predictions from a random-matrix-theory-inspired model. Furthermore, theoretical coupled-channels simulations of the anisotropic molecular Hamiltonian at zero magnetic field show that weakly bound, near threshold diatomic levels form overlapping, uncoupled chaotic series that when combined are randomly distributed. The Zeeman interaction shifts and couples these levels, leading to a Feshbach spectrum of zero-energy bound states with nearest-neighbor spacings that changes from randomly to chaotically distributed for increasing magnetic field. Finally, we show that the extreme temperature sensitivity of a small, but sizable fraction of the resonances in the Dy and Er atom-loss spectra is due to resonant nonzero partial-wave collisions. Our threshold analysis for these resonances indicates a large collision-energy dependence of the three-body recombination rate.

  11. Crystal field and magnetic properties of ErH3

    NASA Technical Reports Server (NTRS)

    Flood, D. J.

    1977-01-01

    Magnetization and magnetic susceptibility measurements have been made in the temperature range 1.3 to 4.2 K on powdered samples of ErH3. The susceptibility exhibits Curie-Weiss behavior from 4.2 to 2 K, and intercepts the negative temperature axis at 1.05 + or - 0.05 K, indicating that the material is antiferromagnetic. The low field effective moment is 6.77 + or - 0.27 Bohr magnetons per ion. The magnetization exhibits a temperature independent contribution, the slope of which is (5 + or - 1.2) times 10 to the minus 6 Weber m/kg Tesla. The saturation moment is 3.84 + or - 0.15 Bohr magnetons per ion. The results can be qualitatively explained by the effects of crystal fields on the magnetic ions. No definitive assignment of a crystal field ground state can be given, nor can a clear choice between cubically or hexagonally symmetric crystal fields be made. For hexagonal symmetry, the first excited state is estimated to be 86 to 100 K above the ground state. For cubic symmetry, the splitting is of the order of 160 to 180 K.

  12. Evolution of mechanical properties in ErT2 films.

    SciTech Connect

    Browning, James Frederick; Bond, Gillian Mary; Knapp, James Arthur

    2010-04-01

    The mechanical properties of rare earth tritide films evolve as tritium decays into {sup 3}He, which forms bubbles that influence long-term film stability in applications such as neutron generators. Ultralow load nanoindentation, combined with finite-element modeling to separate the mechanical properties of the thin films from their substrates, has been used to follow the mechanical properties of model ErT{sub 2} films as they aged. The size of the growing {sup 3}He bubbles was followed with transmission electron microscopy, while ion beam analysis was used to monitor total T and {sup 3}He content. The observed behavior is divided into two regimes: a substantial increase in layer hardness but elasticity changed little over {approx}18 months, followed by a decrease in elastic stiffness and a modest decease in hardness over the final 24 months. We show that the evolution of properties is explained by a combination of dislocation pinning by the bubbles, elastic softening as the bubbles occupy an increasing fraction of the material, and details of bubble growth modes.

  13. Completion Report for Well ER-7-1

    SciTech Connect

    Bechtel Nevada

    2004-11-01

    Well ER-7-1 was drilled for the U.S. Department of Energy's National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well was drilled in January and February 2003, as part of a hydrogeologic investigation program in Yucca Flat. A 47.0-centimeter surface hole was drilled and cased off to a depth of 541.0 meters below the surface. The hole diameter was then decreased to 31.8 centimeters for drilling to a total depth of 762.0 meters. Detailed lithologic descriptions with stratigraphic assignments are included in this report. These are based on composite drill cuttings collected every 3 meters, and 62 sidewall samples taken at various depths below 85.3 meters, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies were conducted on 22 samples of cuttings. The well was collared in Quaternary surficial deposits and penetrated a thick section of Tertiary-age volcanic deposits before terminating in carbonate rocks of Paleozoic-age.

  14. Stratospheric constituent trends from ER-2 profile data

    NASA Technical Reports Server (NTRS)

    Schoeberl, Mark R.; Proffitt, Michael H.; Kelly, Ken K.; Lait, Leslie R.; Newman, Paul A.; Rosenfield, Joan E.; Loewenstein, Max; Podolske, Jim R.; Strahan, Susan E.; Chan, K. Roland

    1990-01-01

    Trend analysis of the Airborne Arctic Stratospheric Expedition's ER-2 profile data reveals an average decrease in N2O on potential temperature isentropes which can be attributed to diabatic cooling of inner vortex air. This conclusion is independently supported by radiative transfer computations. Trends in ozone and water vapor over the same period are not consistent with the magnitude of the diabatic descent. After accounting for the diabatic motion (estimated from N2O), an additional 0.44 + or - 0.3 percent/day average anomalous O3 decrease above 440 K (about 20 km) is needed to balance the continuity equation. This ozone decrease suggests additional photochemical destruction of ozone in the presence of the high amounts of ClO observed during the mission. A 0.4 + or - 0.3 percent/day average anomalous increase in H2O is also observed near 420 K (about 18 km) which may be due to the evaporation of ice crystals falling from higher, colder stratospheric layers.

  15. Pullulanibacillus pueri sp. nov., isolated from Pu'er tea.

    PubMed

    Niu, Lili; Tang, Tianyi; Song, Lei; Xiong, Mengjie; Tian, Jianqing; Zhang, Kegui; Hu, Xing; Zhu, Daochen

    2015-07-01

    A novel Gram-stain-positive, aerobic, endospore-forming, rod-shaped bacterial strain YN3(T) was isolated from ripened Pu'er tea. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belonged to the family Sporolactobacillaceae and was closely related to Pullulanibacillus naganoensis DSM 10191(T) (95.8% 16S rRNA gene sequence similarity) and Pullulanibacillus uraniitolerans DSM 19429(T) (95.4%). Growth of the strain was observed at 20-50 C (optimum 30-37 C), at pH 4.0-8.0 (optimum pH 5.0-6.0). The strain had a cell-wall type A1? peptidoglycan with meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinone was menaquinone-7 (MK-7). The major fatty acids were anteiso-C15:0, anteiso-C17:0 and C18:1?7c. The DNA G+C content of strain YN3(T) was 38.7 mol%. Strain YN3(T) could be differentiated from recognized species of the genus Pullulanibacillus based on phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA hybridization data. On the basis of polyphasic evidence from this study, Pullulanibacilluspueri sp. nov., is proposed, with strain YN3(T) (?= CGMCC 1.12777(T ) = JCM 30075(T)) as the type strain. PMID:25858244

  16. [Physicians in the TV soap--a study of ER].

    PubMed

    Nielsen, Rune; Baerheim, Anders

    2005-12-15

    Health providers are constantly exposed to patients' cultural expressions. Television is a central agent forming our cultural surroundings. The aim of this study has been to elucidate how a specific genre - the medical soap opera - represents the health system, and shape our expectations of it. The first part of the study is a genre analysis based on media science, literary theory and narrative-based medicine. The second part of the study applies these theoretical elements on the series Emergency Room (ER). Using text analysis, one episode was reviewed in detail. The medical soap opera is a genre characterised by qualities such as a narration, its focus on the physician in her professional role and as a private individual, and by a glamour medical reality. These theoretical considerations support how soap operas focus on the physician as a type and a causally stringent construction of the narrative. The narrative qualities of the soap opera are found to satisfy people's desire for more causality in daily life. Wish fulfillment is a central function of the soap opera. In sum, medical soap operas fulfill a desire for a more comprehensive health system, showing health actors as human beings rather than just white coats. PMID:16357895

  17. Structure and function of ER membrane contact sites with other organelles.

    PubMed

    Phillips, Melissa J; Voeltz, Gia K

    2016-02-01

    The endoplasmic reticulum (ER) is the largest organelle in the cell, and its functions have been studied for decades. The past several years have provided novel insights into the existence of distinct domains between the ER and other organelles, known as membrane contact sites (MCSs). At these contact sites, organelle membranes are closely apposed and tethered, but do not fuse. Here, various protein complexes can work in concert to perform specialized functions such as binding, sensing and transferring molecules, as well as engaging in organelle biogenesis and dynamics. This Review describes the structure and functions of MCSs, primarily focusing on contacts of the ER with mitochondria and endosomes. PMID:26627931

  18. Erbium nanoparticle doped fibers for efficient, resonantly-pumped Er-doped fiber lasers

    NASA Astrophysics Data System (ADS)

    Friebele, E. Joseph; Baker, Colin C.; Askins, Charles G.; Fontana, Jake P.; Hunt, Michael P.; Peele, John R.; Marcheschi, Barbara A.; Oh, Euneku; Kim, Woohong; Sanghera, Jasbinder; Zhang, Jun; Pattnaik, Radha K.; Merkle, Larry D.; Dubinskii, Mark

    2015-03-01

    Nanoparticle (NP) doping is a new technique for making erbium-doped fibers (EDFs); the Er ions are surrounded by a cage of aluminum and oxygen ions, substantially reducing Er3+ ion-ion energy exchange and its deleterious effects on laser performance. Er-Al-doped NPs have been synthesized and doped in-situ into the silica soot of the preform core. We report the first known measurements of NP-doped EDFs in a resonantly-core pumped master oscillator-power amplifier (MOPA) configuration; the optical-to-optical slope efficiency was 80.4%, which we believe is a record for this type of fiber.

  19. Magnetic properties and magnetocaloric effect in quaternary boroncarbides compound ErNiBC

    NASA Astrophysics Data System (ADS)

    Zhang, Yikun; Wilde, Gerhard

    2015-09-01

    The magnetocaloric effect (MCE) of quaternary intermetallic compound ErNiBC has been investigated by magnetization and heat capacity measurements. The compound undergoes a paramagnetic (PM) to ferromagnetic (FM) transition at TC~5 K and the ground state of Er ion forms a Kramer's doublet state. The magnetic transition is found to be second order in nature. The maximum magnetic entropy change (-?SMmax) and adiabatic temperature change (?Tadmax) of ErNiBC are 24.8 J/kg K and 8.6 K, respectively, for a magnetic field change of 0-50 kOe, and the corresponding refrigerant capacity (RC) is 312 J/kg.

  20. Vortex pinning by magnetic order in ErNi2B2C

    NASA Astrophysics Data System (ADS)

    Dewhurst, C. D.; James, S. S.; Doyle, R. A.; Paltiel, Y.; Shtrikman, H.; Zeldov, E.; Paul, D. McK.

    2001-02-01

    We have used a miniature linear Hall probe array to make local magnetization measurements of the magnetic superconductor ErNi2B2C (Tc~=10.8 K). We show the sharp onset of significant pinning effects in ErNi2B2C is coincident with the onset of an a-axis incommensurate ordering of the Er moments at Tma~=6 K, below Tc. The data presented provide further evidence that certain components of the magnetic order in (R)Ni2B2C materials interact with the vortex lattice and have a profound influence on the nonequilibrium (vortex pinning) properties of the superconducting state.

  1. Transport Anisotropy in ErNi2B2C Along c-AXIS

    NASA Astrophysics Data System (ADS)

    Lee, W. C.

    The resistivities along c-axis ?c(H, T) of ErNi2 B2C have been measured with H? and H? c-axis for 2 < T < 300 K and the superconducting upper critical field Hc2(T) curves of ErNi2B2C were constructed for each magnetic fields. Our Hc2(T) curves have been compared and discussed with those from ?ab(H, T) measurements which explain the anisotropy and its temperature dependence of Hc2(T) are thought to arise from magnetic pair breaking and the anisotropic field dependence of Nel temperature TN originated from Er+3 sublattice.

  2. A Systematic In Silico Mining of the Mechanistic Implications and Therapeutic Potentials of Estrogen Receptor (ER)-α in Breast Cancer

    PubMed Central

    Lu, Bangmin; Li, Xiaoyu; Wang, Zijie; Bao, Jinku

    2014-01-01

    Estrogen receptor (ER)-α has long been a potential target in ER-α-positive breast cancer therapeutics. In this study, we integrated ER-α-related bioinformatic data at different levels to systematically explore the mechanistic and therapeutic implications of ER-α. Firstly, we identified ER-α-interacting proteins and target genes of ER-α-regulating microRNAs (miRNAs), and analyzed their functional gene ontology (GO) annotations of those ER-α-associated proteins. In addition, we predicted ten consensus miRNAs that could target ER-α, and screened candidate traditional Chinese medicine (TCM) compounds that might hit diverse conformations of ER-α ligand binding domain (LBD). These findings may help to uncover the mechanistic implications of ER-α in breast cancer at a systematic level, and provide clues of miRNAs- and small molecule modulators- based strategies for future ER-α-positive breast cancer therapeutics. PMID:24614816

  3. Contribution of estrogen receptor subtypes, ER?, ER?, and GPER1 in rapid estradiol-mediated enhancement of hippocampal synaptic transmission in mice.

    PubMed

    Kumar, Ashok; Bean, Linda A; Rani, Asha; Jackson, Travis; Foster, Thomas C

    2015-12-01

    Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3-5-month-old wild type (WT), estrogen receptor alpha (ER?KO), and beta (ER?KO) knockout female ovariectomized mice. Hippocampal slices were prepared 10-16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts before and following application of 17?-estradiol-3-benzoate (EB, 100 pM), the G-protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ER? selective agonist propyl pyrazole triol (PPT, 100 nM), or the ER? selective agonist diarylpropionitrile (DPN, 1 M). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB-mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ER? and ER? selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal-regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes. 2015 Wiley Periodicals, Inc. PMID:25980457

  4. Flavonoids from Herba epimedii selectively activate estrogen receptor alpha (ER?) and stimulate ER-dependent osteoblastic functions in UMR-106 cells.

    PubMed

    Xiao, Hui-Hui; Fung, Chung-Yan; Mok, Sao-King; Wong, Ka-Chun; Ho, Ming-Xian; Wang, Xin-Luan; Yao, Xin-Sheng; Wong, Man-Sau

    2014-09-01

    Total flavonoids in Herba epimedii (HEP) have been demonstrated to protect against bone loss and bone deterioration associated with estrogen deficiency without exerting any uterotrophic effects. However, it is unclear how flavonoids in HEP exert their protective effects on bone and if different flavonoids exert estrogenic actions in bone cells via similar mechanism of actions. The present study aims to investigate the bone anabolic effects of four major flavonoids isolated from HEP, namely icariin, baohuoside-I, epimedin B and sagittatoside A as well as the mechanism involved in mediating their estrogenic actions in rat osteoblastic-like UMR-106 cells. All tested compounds significantly stimulated the cell proliferation rate, alkaline phosphate (ALP) activity and osteoprotegerin (OPG)/receptor activator of nuclear factor ?-B ligand (RANKL) mRNA expression in UMR-106 cells and their effects could be abolished by co-incubation with 10(-6)M ICI 182,780. None of the flavonoids exhibited binding affinities toward ER? and ER?. However, sagittatoside A selectively activated estrogen response element (ERE)-luciferase activity via ER?. In addition, icariin and sagittatoside A induced ER? phosphorylation at serine 118 residue. Taken together, our results indicated that all four flavonoids from HEP stimulated ER-dependent osteoblastic functions in UMR-106 cells, but only two of them appeared to exert their actions by ligand-independent activation of ER?. Our study provides evidence to support the hypothesis that the estrogen-like protective effects on bone by flavonoids are mediated via mechanisms that are distinct from the classical actions of estrogen. PMID:24607839

  5. Reduction of the 1.55 m Er3+ emission band half-width in Er doped and Er/Yb co-doped oxy-fluoride glass-ceramics fibers

    NASA Astrophysics Data System (ADS)

    Augustyn, E.; ?elechower, M.; Czerska, E.; ?widerska, M.; Soza?ska, M.

    2014-05-01

    In earlier papers the authors have shown by XRD measurements and HRTEM imaging/SAED (selected area electron diffraction)/STEM imaging/EDS X-ray spectra that erbium or erbium/ytterbium-enriched nano-crystals are formed in erbium doped and erbium/ytterbium co-doped oxy-fluoride glass-ceramics fibers by their controlled heat-treatment. By the analysis of XRD, HRTEM and SAED patterns three crystalline compounds have been identified (Pb5Al3F19, Er4F2O11Si3, Er3FO10Si3). Additionally, STEM imaging combined with EDS X-ray analysis revealed higher erbium/ytterbium content in nano-crystals than in glassy host. According to several reports on homogeneous/inhomogeneous broadening of emission lines we can expect in glass-ceramics material the distinct reduction of the 1.55 ?m Er3+ linewidth (FWHM) as a consequence of structurally ordered (crystalline) vicinity of erbium ions in glass-ceramics fibers. Additionally the Stark splitting of Er3+ ions sub-levels should be observed due to the crystalline electric field surrounding the erbium ion, which lifts the atomic state degeneracy, however identified crystals possess rather low symmetry (monoclinic or triclinic unit cell).

  6. ER? up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells.

    PubMed

    Zheng, Nan; Liu, Lu; Liu, Weiwei; Zhang, Ping; Huang, Huai; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-Ichi; Onodera, Satoshi; Xia, Mingyu; Ikejima, Takashi

    2016-02-01

    We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ER? down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ER?, has yet to be elucidated. Therefore, we sought to explore the effects of ER? modulation on cell viability by using an ER?-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ER? served as a growth suppressor in MCF-7cells, and the incubation of silibinin, elevated ER? expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ER? by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and -6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ER?, ER? did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ER? activity. Taken together, silibinin induced apoptosis through mitochondrial pathway by up-regulating ER? pathways in MCF-7cells without the involvement of autophagy. PMID:26767948

  7. Completion Report for Wells ER-20-8 and ER-20-8#2 Corrective Action Units 101 and 102: Central and Western Pahute Mesa

    SciTech Connect

    NSTec Environmental Management

    2011-02-28

    Wells ER-20-8 and ER-20-8#2 were drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada National Security Site (formerly Nevada Test Site), Nye County, Nevada. The holes were drilled in July and August 2009, as part of the Pahute Mesa Phase II drilling program. The primary purpose of these wells was to provide detailed hydrogeologic information in the Tertiary volcanic section that will help address uncertainties within the Pahute Mesa–Oasis Valley hydrostratigraphic framework model. They may also be used as long-term monitoring wells.

  8. Design and control of 4 DOF ER haptic master for medical application

    NASA Astrophysics Data System (ADS)

    Oh, Jong-Seok; Cho, Han-Jun; Han, Young-Min; Choi, Seung-Bok

    2012-04-01

    In this research, a new type of haptic master device using electrorheological (ER) fluid for minimally invasive surgery (MIS) is proposed. The proposed haptic master consists of an ER spherical joint for 3-DOF rotational motion (X, Y, Z) and an ER brake for 1-DOF translational motion (Z). Principal design parameters of the haptic master are determined based on Bingham characteristic of ER fluid and geometrical constraints. In order to demonstrate the effectiveness of the proposed haptic master, control performance is evaluated. In order to achieve desired force trajectories, a sliding mode controller (SMC) is designed and implemented. Both torque and force tracking control performances show that the proposed haptic master can be effectively applied to surgical robot system.

  9. Many Kidney Transplant Patients Land in ER Within 2 Years: Study

    MedlinePLUS

    ... news/fullstory_157959.html Many Kidney Transplant Patients Land in ER Within 2 Years: Study Findings show need to coordinate care after organ transplant, researcher says To use the sharing features on this page, please enable ...

  10. Arctic geodynamics: Continental shelf and deep ocean geophysics. ERS-1 satellite altimetry: A first look

    NASA Technical Reports Server (NTRS)

    Anderson, Allen Joel; Sandwell, David T.; Marquart, Gabriele; Scherneck, Hans-Georg

    1993-01-01

    An overall review of the Arctic Geodynamics project is presented. A composite gravity field model of the region based upon altimetry data from ERS-1, Geosat, and Seasat is made. ERS-1 altimetry covers unique Arctic and Antarctic latitudes above 72 deg. Both areas contain large continental shelf areas, passive margins, as well as recently formed deep ocean areas. Until ERS-1 it was not possible to study these areas with satellite altimetry. Gravity field solutions for the Barents sea, portions of the Arctic ocean, and the Norwegian sea north of Iceland are shown. The gravity anomalies around Svalbard (Spitsbergen) and Bear island are particularly large, indicating large isostatic anomalies which remain from the recent breakup of Greenland from Scandinavian. Recently released gravity data from the Armed Forces Topographic Service of Russia cover a portion of the Barents and Kara seas. A comparison of this data with the ERS-1 produced gravity field is shown.

  11. Jagn1 Is Induced in Response to ER Stress and Regulates Proinsulin Biosynthesis

    PubMed Central

    Nosak, Courtney; Silva, Pamuditha N.; Sollazzo, Pietro; Moon, Kyung-Mee; Odisho, Tanya; Foster, Leonard J.; Rocheleau, Jonathan V.; Volchuk, Allen

    2016-01-01

    The Jagn1 protein was indentified in a SILAC proteomic screen of proteins that are increased in insulinoma cells expressing a folding-deficient proinsulin. Jagn1 mRNA was detected in primary rodent islets and in insulinoma cell lines and the levels were increased in response to ER stress. The function of Jagn1 was assessed in insulinoma cells by both knock-down and overexpression approaches. Knock-down of Jagn1 caused an increase in glucose-stimulated insulin secretion resulting from an increase in proinsulin biosynthesis. In contrast, overexpression of Jagn1 in insulinoma cells resulted in reduced cellular proinsulin and insulin levels. Our results identify a novel role for Jagn1 in regulating proinsulin biosynthesis in pancreatic β-cells. Under ER stress conditions Jagn1 is induced which might contribute to reducing proinsulin biosynthesis, in part by helping to relieve the protein folding load in the ER in an effort to restore ER homeostasis. PMID:26882284

  12. Structural and photoluminescence properties of Ce, Dy, Er-doped ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Jayachandraiah, C.; Kumar, K. Siva; Krishnaiah, G.

    2015-06-01

    Undoped ZnO and rare earth elements (Ce, Dy and Er with 2 at. %) doped nanoparticles were synthesized by wet chemical co-precipitation method at 90°C with Polyvinylpyrrolidone (PVP) as capping agent. The structural, morphological, compositional and photoluminescence studies were performed with X-ray diffraction (XRD), Transmission electron microscopy (TEM), Energy dispersive spectroscopy (EDS), FTIR spectroscopy and Photoluminescence (PL) respectively. XRD results revealed hexagonal wurtzite structure with average particle size around 18 nm - 14 nm and are compatible with TEM results. EDS confirm the incorporation of Ce, Dy and Er elements into the host ZnO matrix and is validated by FTIR analysis. PL studies showed a broad intensive emission peak at 558 nm in all the samples. The intensity for Er- doped ZnO found maximum with additional Er shoulder peaks at 516nm and 538 nm. No Ce, Dy emission centers were found in spectra.

  13. Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain.

    PubMed

    Grigaravicius, P; Kaminska, E; Hbner, C A; McKinnon, P J; von Deimling, A; Frappart, P-O

    2016-03-01

    Endoplasmic reticulum (ER) stress, defective autophagy and genomic instability in the central nervous system are often associated with severe developmental defects and neurodegeneration. Here, we reveal the role played by Rint1 in these different biological pathways to ensure normal development of the central nervous system and to prevent neurodegeneration. We found that inactivation of Rint1 in neuroprogenitors led to death at birth. Depletion of Rint1 caused genomic instability due to chromosome fusion in dividing cells. Furthermore, Rint1 deletion in developing brain promotes the disruption of ER and Cis/Trans Golgi homeostasis in neurons, followed by ER-stress increase. Interestingly, Rint1 deficiency was also associated with the inhibition of the autophagosome clearance. Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy. PMID:26383973

  14. Sampling and Analysis Plan for Catch Tank 241ER311 Vapor

    SciTech Connect

    NGUYEN, D.M.

    1999-11-05

    This tank sampling and analysis plan (TSAP) identifies the sample collection, laboratory analysis, quality assurance/quality control (QA/QC) objectives for the characterization of catch tank 241-ER-311 vapor space.

  15. Sampling and Analysis Plan for Catch Tank 241ER311 Vapor

    SciTech Connect

    NGUYEN, D.M.

    1999-11-09

    This tank sampling and analysis plan (TSAP) identifies the sample collection, laboratory analysis, quality assurance/quality control (QA/QC) objectives for the characterization of catch tank 241-ER-311 vapor space.

  16. Spontaneous emission rate and optical amplification of Er3+ in double slot waveguide

    NASA Astrophysics Data System (ADS)

    Wang, XingJun; Jiang, LingJun; Guo, RuiMin; Ye, Rui; Zhou, ZhiPing

    2015-12-01

    The spontaneous emission (SE) of Er3+ embedded in a double slot dielectric structure was studied by a quantum-electrodynamical formalism. The study shows that the slot width and the position of Er3+ in slot structure have a significant effect on the SE. The double slot waveguides were fabricated by embedding two low-index Er/Yb silicate material layers into high-index silicon. The radiative efficiency of Er3+ in the double slot waveguides is found to be higher than that of the single slot waveguide, which is consistent with the theory simulation. The 0.67 dB signal enhancement at 1.53 m in a 4.6-mm-long slot waveguide was observed pumped by 1476 nm laser. These results show the relevance of our model to study the SE processes in multilayer structures and are important for future realization of silicon-compatible active optical devices.

  17. Robot Arm Control Using AN Electro-Rheological (er) Clutch-Brake Mechanism:. Model Validation

    NASA Astrophysics Data System (ADS)

    Tan, K. P.; Stanway, R.; Bullough, W. A.

    Robot arm positioning is an important factor in the robotic process. However, the robot manipulator experiences positioning inaccuracies. This positioning error is due to the dynamic inefficiencies of its actuator: DC servomotor. In a bid to resolve this actuator problem, an electro-rheological (ER) clutch-brake mechanism is employed. This clutch-brake mechanism can actuate and halt the motion of the robot arm. This rotary mechanism consists of two similar clutches that are driven to rotate in the opposite directions and an individual ER brake that provides braking torques to halt the manipulator at the required positions. The main aim of this paper is to establish a control strategy for the ER actuated robot arm by means of model validation with the experimental results. This study is conducted to understand the ER robotic positioning control for future applications.

  18. Er:YAG laser: clinical experience based upon scientific evidence: clinical cases

    NASA Astrophysics Data System (ADS)

    Zanin, Fatima A. A.; Brugnera, Aldo, Jr.; Pecora, Jesus D.; Pinheiro, Antonio L. B.; Souza-Campos, Dilma H.; Vieira de Medeiros, Urubatan

    2001-04-01

    The aim of this work was to demonstrate, based upon scientific evidence, the efficacy of dental treatment using the Er:YAG laser. The Er:YAG laser is able of quick cavitation of dental structure with minimal thermal effect. It is also well known that most treatment is carried out without the need of local anesthesia. It is also recognized that its work with no vibration and in a non-contact mode. This paper reports the clinical results of 590 dental procedures carried out with the Er:YAG laser on selected patients. The laser was used for composite removal, cavity enamel preparation, carious dentine removal and conditioning of both dentin and enamel. Dental treatment with the Er:YAG laser as a secure and efficient method of treatment with more comfort for the patients, high acceptance form patients and less need of using local anesthesia.

  19. Temperature dependence of sensitized Er3+ luminescence in silicon-rich oxynitride films

    PubMed Central

    2014-01-01

    The temperature dependence of sensitized Er3+ emission via localized states and silicon nanoclusters has been studied to get an insight into the excitation and de-excitation processes in silicon-rich oxynitride films. The thermal quenching of Er3+ luminescence is elucidated by terms of decay time and effective excitation cross section. The temperature quenching of Er3+ decay time demonstrates the presence of non-radiative trap states, whose density and energy gap between Er3+4I13/2 excited levels are reduced by high-temperature annealing. The effective excitation cross section initially increases and eventually decreases with temperature, indicating that the energy transfer process is phonon assisted in both samples. PMID:25258608

  20. Tank 241ER311 Interconnected Piping and Equipment Vapor Sampling and Analysis Plan

    SciTech Connect

    SASAKI, L.M.

    1999-11-05

    This sampling and analysis plan (SAP) identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for vapor samples obtained from piping, equipment, or facilities connected to tank 241-ER-311. The purpose of this sampling event is to obtain information about the effects of the argon purge gas added to tank 241-ER-311. Vapor samples will be taken in the encasement of transfer lines, at the ER-151 diversion box, and, as necessary, any other locations connected to tank 241-ER-311. Combustible gas, ammonia, and organic vapor levels will be field-measured using hand-held instruments. Vapor samples will be taken and shipped to the Pacific Northwest National Laboratory (PNNL) for analysis. This test plan identifies the sample collection, laboratory analysis, quality assurance, and reporting objectives for this data collection effort. The plan also provides the requirements for vapor measurements performed in the field.