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Sample records for raske overvaegtige er

  1. Going to the ER

    MedlinePLUS

    ... ACPA Contact Us Shop FAQs The Art of Pain Management Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to Chronic Pain Treatments Pain ...

  2. 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.

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

    PubMed

    Greig, Sarah L; Keating, Gillian M

    2015-07-01

    Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(®), Mysimba(™)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of ≥ 30 kg/m(2) (i.e. obese) or a BMI of ≥ 27 kg/m(2) (i.e. overweight) in the presence of at least one bodyweight-related comorbidity, such as type 2 diabetes mellitus, hypertension or dyslipidaemia. In 56-week phase III trials in these patient populations, oral naltrexone ER/bupropion ER 32/360 mg/day was significantly more effective than placebo with regard to percentage bodyweight reductions from baseline and the proportion of patients who achieved bodyweight reductions of ≥ 5 and ≥ 10%. Significantly greater improvements in several cardiometabolic risk factors were also observed with naltrexone ER/bupropion ER versus placebo, as well as greater improvements in glycated haemoglobin levels in obese or overweight adults with type 2 diabetes. Naltrexone ER/bupropion ER was generally well tolerated in phase III trials, with nausea being the most common adverse event. Thus, naltrexone ER/bupropion ER 32/360 mg/day as an adjunct to a reduced-calorie diet and increased physical activity, is an effective and well tolerated option for chronic bodyweight management in obese adults or overweight adults with at least one bodyweight-related comorbidity. PMID:26105116

  4. 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.

  5. 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…

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics.

    PubMed

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

    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

  12. 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

  13. 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

  14. 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

  15. ER stress and effects of DHA as an ER stress inhibitor

    PubMed Central

    Begum, Gulnaz; Harvey, Lloyd; Dixon, C. Edward; Sun, Dandan

    2013-01-01

    The endoplasmic reticulum (ER) functions in the synthesis, folding, modification, and transport of newly synthesized transmembrane and secretory proteins. The ER also has important roles in the storage of intracellular Ca2+ and regulation of Ca2+ homeostasis. The integrity of the Ca2+ homeostasis in the ER lumen is vital for proper folding of proteins. A dysregulation of ER Ca2+ could result in an increase in unfolded or misfolded proteins and ER stress. ER stress triggers activation of the unfolded protein response (UPR), which is a fundamentally adaptive cell response and functions as a cytoprotective mechanism by over-expression of relevant chaperones and the global shutdown of protein synthesis. UPR activation occurs when three key ER membrane-sensor proteins detect an accumulation of aberrant proteins. The UPR acts to allievate ER stress, but if the stress is too severe or prolonged, apoptosis will be triggered. In this review, we focused on ER stress and the effects of docosahexaenoic acid (DHA) on ER stress. DHA and its bioactive compounds, such as protectins and resolvins, provide neuroprotection against oxidative stress, apoptosis, and have the ability to resolve inflammation in neurological diseases. New studies reveal that DHA blocks inositol trisphosphate receptor (IP3R)-mediated ER Ca2+ depletion and ER stress. The administration of DHA post-traumatic brain injury (TBI) reduces ER stress, aberrant protein accumulation, and neurological deficits. Therefore, DHA presents therapeutic potentials for TBI via its pleiotropic effects including inhibition of ER stress. PMID:24323417

  16. 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 K–300 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.

  17. The ER under rapid fire

    PubMed Central

    Schwenk, Benjamin M; Edbauer, Dieter

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to selective death of upper and lower motoneurons. Clinically, the ALS syndrome is linked to pathogenic mutations in superoxide dismutase 1 (SOD1), though actual molecular mechanisms remain ill understood. Two papers recently published in Cell Stem Cell and Cell Reports employ syngenic, iPSC-derived cell lines of one of the most severe SOD1 mutations to report mitochondrial and ER stress as causal for perturbed electrical activity in ALS neurons (Kiskinis et al, 2014; Wainger et al, 2014). PMID:24788411

  18. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    PubMed Central

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

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  19. Estrogen receptor (ER)-β isoforms: A key to understanding ER-β signaling

    PubMed Central

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

    2006-01-01

    Estrogen receptor beta (ER-β) regulates diverse physiological functions in the human body. Current studies are confined to ER-β1, and the functional roles of isoforms 2, 4, and 5 remain unclear. Full-length ER-β4 and -β5 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-β1 has a full-length helix 11 and a helix 12 that assumes an agonist-directed position. In ER-β2, the shortened C terminus results in a disoriented helix 12 and marked shrinkage in the coactivator binding cleft. ER-β4 and -β5 completely lack helix 12. We further demonstrated that ER-β1 is the only fully functional isoform, whereas ER-β2, -β4, and -β5 do not form homodimers and have no innate activities of their own. However, the isoforms can heterodimerize with ER-β1 and enhance its transactivation in a ligand-dependent manner. ER-β1 tends to form heterodimers with other isoforms under the stimulation of estrogens but not phytoestrogens. Collectively, these data support the premise that (i) ER-β1 is the obligatory partner of an ER-β 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-β behaves like a noncanonical type-I receptor, and its action may depend on differential amounts of ER-β1 homo- and heterodimers formed upon stimulation by a specific ligand. Our findings have provided previously unrecognized directions for studying ER-β signaling and design of ER-β-based therapies. PMID:16938840

  20. Processing effects on microstructure in Er and ErD2 thin-films.

    SciTech Connect

    Kammler, Daniel R.; Parish, Chad; Snow, Clark Sheldon; Brewer, Luke N.

    2010-04-01

    Erbium metal thin-films have been deposited on molybdenum-on-silicon substrates and then converted to erbium dideuteride (ErD{sub 2}). Here, we study the effects of deposition temperature ({approx}300 or 723 K) and deposition rate (1 or 20 nm/s) upon the initial Er metal microstructure and subsequent ErD{sub 2} microstructure. We find that low deposition temperature and low deposition rate lead to small Er metal grain sizes, and high deposition temperature and deposition rate led to larger Er metal grain sizes, consistent with published models of metal thin-film growth. ErD{sub 2} grain sizes are strongly influenced by the prior-metal grain size, with small metal grains leading to large ErD{sub 2} grains. A novel sample preparation technique for electron backscatter diffraction of air-sensitive ErD{sub 2} was developed, and allowed the quantitative measurement of ErD{sub 2} grain size and crystallographic texture. Finer-grained ErD{sub 2} showed a strong (1 1 1) fiber texture, whereas larger grained ErD{sub 2} had only weak texture. We hypothesize that this inverse correlation may arise from improved hydrogen diffusion kinetics in the more defective fine-grained metal structure or due to improved nucleation in the textured large-grain Er.

  1. The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance

    PubMed Central

    Piña, Francisco J; Niwa, Maho

    2015-01-01

    Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases. Protein aggregates are also formed within the endoplasmic reticulum (ER), although the fate of ER protein aggregates, specifically during cell division, is not well understood. By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER. In contrast, under conditions of normal ER inheritance, ER protein aggregates can enter the daughter cell. Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.06970.001 PMID:26327697

  2. Decay of /sup 150/Er

    SciTech Connect

    Moltz, D.M.; Toth, K.S.; Ellis-Akovali, Y.A.; Cole, J.D.

    1982-09-01

    A new activity, T/sub 1/2/ = 20 +- 2 sec, was observed in /sup 12/C bombardments of /sup 144/Sm. Only one ..gamma.. ray, 476.0 +- 0.1 keV, was found to be associated with this nuclide. We identify the new isotope as /sup 150/Er and propose that it decays mainly to one level in /sup 150/Ho at an excitation energy of approx.476 keV by an allowed ..beta.. transition which connects states with the following configurations: O/sup +/(..pi..h/sub 11/2/, ..pi..h/sub 11/2/)..-->..1/sup +/(..pi..h/sub 11/2/,..nu..h/sub 9/2/). As part of the investigation, the decay properties of the high- and low-spin /sup 150/Ho isomers were reexamined.

  3. 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.

  4. Ternary Dy-Er-Al magnetic refrigerants

    DOEpatents

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

    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.

  5. 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.

  6. 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}.

  7. 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

  8. 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.

  9. 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:  ...

  10. 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 ...

  11. 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.

  12. ER Screenings Could Help Prevent Suicide

    MedlinePLUS

    ... fullstory_158246.html ER Screenings Could Help Prevent Suicide: Study Checking patients for risk factors should be ... News) -- Routine screening of emergency room patients for suicide risk might be an effective way to prevent ...

  13. 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.

  14. 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.

  15. Formation energy of optically active Er3+ centers in Er doped GaN

    NASA Astrophysics Data System (ADS)

    Ugolini, C.; Feng, I. W.; Sedhain, A.; Lin, J. Y.; Jiang, H. X.; Zavada, J. M.

    2012-07-01

    Erbium doped GaN (GaN:Er) and low In-content InxGa1-xN (x˜0.05) epilayers were synthesized by metal organic chemical deposition. The 1.54 μm PL emission intensity was monitored for GaN:Er epilayers grown at different growth temperatures and utilized to establish a value of 1.8 ± 0.2 eV for the formation energy (EF) of the optically active Er3+ centers in GaN. The optically active Er+ centers are presumably Er and nitrogen vacancy (Er-VN) complexes. The experimentally measured value of the EF of the optically active Er3+ centers is about 0.98 eV larger than the calculated formation energy of Er ions at Ga sites; however, it is 1.1-2.2 eV lower than the formation energy of VN in GaN. Due to the large EF values, relatively high growth temperatures are required to improve the 1.54 μm emission efficiency in GaN:Er.

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

    PubMed

    Markina-Iñarrairaegui, Ane; Pantazopoulou, Areti; Espeso, Eduardo A; Peñalva, 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

  17. 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

  18. 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

  19. 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 Å 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.

  20. 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

  1. Mechanisms of oestrogen receptor (ER) gene regulation in breast cancer.

    PubMed

    Carroll, J S

    2016-07-01

    Most breast cancers are driven by a transcription factor called oestrogen receptor (ER). Understanding the mechanisms of ER activity in breast cancer has been a major research interest and recent genomic advances have revealed extraordinary insights into how ER mediates gene transcription and what occurs during endocrine resistance. This review discusses our current understanding on ER activity, with an emphasis on several evolving, but important areas of ER biology. PMID:26884552

  2. Intestinal secretory cell ER stress and inflammation.

    PubMed

    McGuckin, Michael A; Eri, Rajaraman D; Das, Indrajit; Lourie, Rohan; Florin, Timothy H

    2011-08-01

    Data from animal models and human inflammatory bowel diseases have implicated the ER (endoplasmic reticulum) stress pathway in intestinal inflammation. We have characterized the development of inflammation in Winnie mice in which ER stress arises due to a single missense mutation in the MUC2 mucin produced by intestinal goblet cells. This model has allowed us to explore the genesis of inflammation ensuing from a single gene polymorphism affecting secretory cells. In these mice, a proportion of MUC2 misfolds during biosynthesis, leading to ER stress and activation of the unfolded protein response. Winnie mice develop spontaneous complex progressive inflammation that is most severe in the distal colon. Inflammation involves TH1, TH2 and TH17 T-cells, with a progressive development of a TH17-dominated response, but also involves innate immunity, in a pattern not dissimilar to human colitis. Experimental inhibition of tolerance in this model severely exacerbates colitis, demonstrating active effective suppression of inflammation. Even though the misfolding of MUC2 is a consequence of an inherited mutation, as inflammation develops, the molecular markers of ER stress increase further and goblet cell pathology becomes worse, suggesting that inflammation itself exacerbates ER stress. PMID:21787352

  3. 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.

  4. 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.

  5. 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…

  6. 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

  7. 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...

  8. 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

  9. 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

  10. The cervical malignant cells display a down regulation of ER-α but retain the ER-β expression

    PubMed Central

    López-Romero, Ricardo; Garrido-Guerrero, Efraín; Rangel-López, Angélica; Manuel-Apolinar, Leticia; Piña-Sánchez, 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-α and ER-β). In this study we investigated the expression of ER-α and ER-β 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-α 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-α is lost in cervical cancer. Nevertheless, by RT-PCR we were able to demonstrate mRNA expression of ER-α in invasive cervical tissues. These results suggest that loss of ER-α 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-β was expressed in normal cervix with an expression pattern similar to ER-α. In addition to its nuclear localization, cytoplasmic immunoreaction of ER-β was present in the epithelium of invasive cervical carcinomas, suggesting an association between cytoplasmic ER-β expression and invasive phenotype in the cervical tumors. In summary, the results show that the cervical malignant cells tend to loss the ER-α but maintain the ER-β actively expressed. Loss of expression of ER-α in neoplastic tissue suggests that the estrogenic effects could be conducted through the ER-β in human neoplastic cervical tissue. More detailed studies are needed to confirm this suggestion and to determine the role of ER-β in cervical cancer. PMID:23923078

  11. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

    PubMed Central

    Chen, Xia; Fu, Xiang-Sheng; Li, Chang-Ping; Zhao, Hong-Xian

    2014-01-01

    AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis. METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry. RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins. CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis. PMID:25009401

  12. 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

  13. 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).

  14. 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).

  15. 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

  16. ER stress, autophagy, and RNA viruses.

    PubMed

    Jheng, Jia-Rong; Ho, Jin-Yuan; Horng, Jim-Tong

    2014-01-01

    Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment. PMID:25140166

  17. Present statue of Japanese ERS-1 Project

    NASA Technical Reports Server (NTRS)

    Ishiwada, Yasufumi; Nemoto, Yoshiaki

    1986-01-01

    Earth Resources Satellite 1 (ERS-1) will be launched in the FY 1990 with the H-1 rocket from Tanegashima Space Center. ERS-1 will seek to firmly establish remote sensing technologies from space by using synthetic aperture radar and optical sensors, as well as primarily exploring for non-renewable resources and also monitoring for land use, agriculture, forestry, fishery, conservation of environment, prevention of disasters, and surveillance of coastal regions. ERS-1 is a joint project in which the main responsibility for the development of the mission equipment is assumed by the Agency of Industrial Science and Technology, MITI, and the Technology Research Association of Resources Remote Sensing System, while that for the satellite itself and launching rocket is assumed by the Science and Technology Agency (STA) and the National Space Development Agency (NASDA). In relation to this project, users have maintained a close working relationship with the manufacturers after submitting their requirements in 1984 on the specifications of the mission equipments. This missions parameters are outlined.

  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. 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

  20. ER stress and the unfolded protein response in intestinal inflammation.

    PubMed

    McGuckin, Michael A; Eri, Rajaraman D; Das, Indrajit; Lourie, Rohan; Florin, Timothy H

    2010-06-01

    Endoplasmic reticulum (ER) stress is a phenomenon that occurs when excessive protein misfolding occurs during biosynthesis. ER stress triggers a series of signaling and transcriptional events known as the unfolded protein response (UPR). The UPR attempts to restore homeostasis in the ER but if unsuccessful can trigger apoptosis in the stressed cells and local inflammation. Intestinal secretory cells are susceptible to ER stress because they produce large amounts of complex proteins for secretion, most of which are involved in mucosal defense. This review focuses on ER stress in intestinal secretory cells and describes how increased protein misfolding could occur in these cells, the process of degradation of misfolded proteins, the major molecular elements of the UPR pathway, and links between the UPR and inflammation. Evidence is reviewed from mouse models and human inflammatory bowel diseases that ties ER stress and activation of the UPR with intestinal inflammation, and possible therapeutic approaches to ameliorate ER stress are discussed. PMID:20338921

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

    PubMed

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

    2015-08-01

    Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death. Among the 4 components to maintain ER homeostasis in β-cells, the role of ER export in insulin biogenesis is the least understood. To address this knowledge gap, the present study investigated the molecular mechanism of proinsulin ER export in MIN6 cells and primary islets. Two inhibitory mutants of the secretion-associated RAS-related protein (Sar)1 small GTPase, known to specifically block coat protein complex II (COPII)-dependent ER export, were overexpressed in β-cells using recombinant adenoviruses. Results from this approach, as well as small interfering RNA-mediated Sar1 knockdown, demonstrated that defective Sar1 function blocked proinsulin ER export and abolished its conversion to mature insulin in MIN6 cells, isolated mouse, and human islets. It is further revealed, using an in vitro vesicle formation assay, that proinsulin was packaged into COPII vesicles in a GTP- and Sar1-dependent manner. Blockage of COPII-dependent ER exit by Sar1 mutants strongly induced ER morphology change, ER stress response, and β-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (p-eIF2α) and inositol-requiring protein 1 (IRE1)/x-box binding protein 1 (Xbp1) pathways but not via activating transcription factor 6 (ATF6). Collectively, results from the study demonstrate that COPII-dependent ER export plays a vital role in insulin biogenesis, ER homeostasis, and β-cell survival. PMID:26083833

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion.

    PubMed

    McCaughey, Janine; Miller, Victoria J; Stevenson, Nicola L; Brown, Anna K; Budnik, Annika; Heesom, Kate J; Alibhai, Dominic; Stephens, David J

    2016-05-24

    Collagen is the most abundant protein in the animal kingdom. It is of fundamental importance during development for cell differentiation and tissue morphogenesis as well as in pathological processes such as fibrosis and cancer cell migration. However, our understanding of the mechanisms of procollagen secretion remains limited. Here, we show that TFG organizes transitional ER (tER) and ER exit sites (ERESs) into larger structures. Depletion of TFG results in dispersion of tER elements that remain associated with individual ER-Golgi intermediate compartments (ERGICs) as largely functional ERESs. We show that TFG is not required for the transport and packaging of small soluble cargoes but is necessary for the export of procollagen from the ER. Our work therefore suggests a key relationship between the structure and function of ERESs and a central role for TFG in optimizing COPII assembly for procollagen export. PMID:27184855

  13. 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

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

    PubMed Central

    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

  15. ESR study of AuEr dilute alloys

    NASA Astrophysics Data System (ADS)

    Dokter, H. D.; Davidov, D.; Hoekstra, F. R.; Nieuwenhuys, G. J.

    1981-06-01

    ESR linewidth and signal intensity measurements of AuEr (0.2%, 1%, 3%) dilute alloys have been carried out as a function of temperature in order to resolve previous discrepancies regarding the crystal field splitting. The data analysis indicates a splitting of (16 ± 4) K between the Γ 7 ground state and the Γ (1)8 first excited state. No evidence for an additional broadening mechanism associated with Er-Er exchange interactions was observed.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Ire1 supports normal ER differentiation in developing Drosophila photoreceptors

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  1. Lanthanum Titanate Nanoparticles ER Fluids with High Performance

    NASA Astrophysics Data System (ADS)

    Wang, De; Shen, Rong; Wei, Shiqiang; Lu, Kunquan

    A new type of electrorheological (ER) fluid consisting of lanthanum titanate (LTO) nanoparticles is developed. The ER fluids were prepared by suspending LTO powder in silicone oil and the particles were fabricated by wet chemical method. This ER fluid shows excellent ER properties: The static yield stress reaches over 150 kPa under 5 kV/mm with linear dependence on the applied DC electric field, and the current density is below 10 μA/cm2. In order to investigate the affect factor on the ER behavior, the LTO powder were heated under different temperatures. The ER performances of two particles treated under different temperatures were compared and the composition changes for those particles were analyzed with TG-FTIR technique. It was found that the static yield stress of the suspensions fell from over 150 kPa to about 40 kPa and the current densities decreased prominently as the rise of the heating temperature. TG-FTIR analysis indicated that polar groups remained in the particles such as alkyl group, hydroxyl group and carbonyl group etc., contribute to the ER effect significantly. The experimental results are helpful to understand the mechanism of the high ER effect and to synthesize better ER materials.

  2. ER stress and development of type 1 diabetes.

    PubMed

    Engin, Feyza

    2016-01-01

    Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease. PMID:26230493

  3. 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

  4. Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts.

    PubMed

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

    2015-05-25

    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 ER-mitochondria and ER-vacuole 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 ER-mitochondria and ER-vacuole 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 ER-mitochondria 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 ER-mitochondria and ER-vacuole contact sites. PMID:25987606

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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 ...

  14. Coronavirus infection, ER stress, apoptosis and innate immunity

    PubMed Central

    Fung, To S.; Liu, Ding X.

    2014-01-01

    The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER). Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR), a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However, under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus–host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP) kinase activation, autophagy, apoptosis, and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize the current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling. PMID:24987391

  15. The manifestation of oxygen contamination in ErD2.

    SciTech Connect

    Snow, Clark Sheldon; Parish, Chad Michael; Brewer, Luke N.

    2008-10-01

    Erbium dihydride Er(H,D,T){sub 2} is a fluorite structure rare-earth dihydride useful for the storage of hydrogen isotopes in the solid state. However, thermodynamic predictions indicate that erbium oxide formation will proceed readily during processing, which may detrimentally contaminate Er(H,D,T){sub 2} films. In this work, transmission electron microscopy (TEM) techniques including energy-dispersive x-ray spectroscopy, energy-filtered TEM, selected area electron diffraction, and high-resolution TEM are used to examine the manifestation of oxygen contamination in ErD{sub 2} thin films. An oxide layer {approx}30-130 nm thick was found on top of the underlying ErD{sub 2} film, and showed a cube-on-cube epitaxial orientation to the underlying ErD{sub 2}. Electron diffraction confirmed the oxide layer to be Er{sub 2}O{sub 3}. While the majority of the film was observed to have the expected fluorite structure for ErD{sub 2}, secondary diffraction spots suggested the possibility of either nanoscale oxide inclusions or hydrogen ordering. In situ heating experiments combined with electron diffraction ruled out the possibility of hydrogen ordering, so epitaxial oxide nanoinclusions within the ErD{sub 2} matrix are hypothesized. TEM techniques were applied to examine this oxide nanoinclusion hypothesis.

  16. 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.

  17. 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

  18. 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

  19. Activation of SK2 channels preserves ER Ca(2+) homeostasis and protects against ER stress-induced cell death.

    PubMed

    Richter, M; Vidovic, N; Honrath, B; Mahavadi, P; Dodel, R; Dolga, A M; Culmsee, C

    2016-05-01

    Alteration of endoplasmic reticulum (ER) Ca(2+) homeostasis leads to excessive cytosolic Ca(2+) accumulation and delayed neuronal cell death in acute and chronic neurodegenerative disorders. While our recent studies established a protective role for SK channels against excessive intracellular Ca(2+) accumulation, their functional role in the ER has not been elucidated yet. We show here that SK2 channels are present in ER membranes of neuronal HT-22 cells, and that positive pharmacological modulation of SK2 channels with CyPPA protects against cell death induced by the ER stressors brefeldin A and tunicamycin. Calcium imaging of HT-22 neurons revealed that elevated cytosolic Ca(2+) levels and decreased ER Ca(2+) load during sustained ER stress could be largely prevented by SK2 channel activation. Interestingly, SK2 channel activation reduced the amount of the unfolded protein response transcription factor ATF4, but further enhanced the induction of CHOP. Using siRNA approaches we confirmed a detrimental role for ATF4 in ER stress, whereas CHOP regulation was dispensable for both, brefeldin A toxicity and CyPPA-mediated protection. Cell death induced by blocking Ca(2+) influx into the ER with the SERCA inhibitor thapsigargin was not prevented by CyPPA. Blocking the K(+) efflux via K(+)/H(+) exchangers with quinine inhibited CyPPA-mediated neuroprotection, suggesting an essential role of proton uptake and K(+) release in the SK channel-mediated neuroprotection. Our data demonstrate that ER SK2 channel activation preserves ER Ca(2+) uptake and retention which determines cell survival in conditions where sustained ER stress contributes to progressive neuronal death. PMID:26586570

  20. 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

  1. SR/ER-mitochondrial local communication: Calcium and ROS

    PubMed Central

    Csordás, György; Hajnóczky, György

    2009-01-01

    Mitochondria form junctions with the sarco/endoplasmic reticulum (SR/ER), which support signal transduction and biosynthetic pathways and affect organellar distribution. Recently, these junctions have received attention because of their pivotal role in mediating calcium signal propagation to the mitochondria, which is important for both ATP production and mitochondrial cell death. Many of the SR/ER-mitochondrial calcium transporters and signaling proteins are sensitive to redox regulation and are directly exposed to the reactive oxygen species (ROS) produced in the mitochondria and SR/ER. Although ROS has been emerging as a novel signaling entity, the redox signaling of the SR/ER-mitochondrial interface is yet to be elucidated. We describe here possible mechanisms of the mutual interaction between local Ca2+ and ROS signaling in the control of SR/ER-mitochondrial function. PMID:19527680

  2. 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.

  3. 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.

  4. Diammonium phosphate modified titanium dioxide suspensions with improved ER efficiency

    NASA Astrophysics Data System (ADS)

    Ma, Ning; Dong, Xufeng

    2015-06-01

    Electrorheological (ER) efficiency is an important parameter that should be considered for applications of electrorheologcial fluids. In this study, diammonium phosphate ((NH4)2HPO4, DAP) is used to modify titanium dioxide particles. The structures and morphologies of the DAP modified particles are not significantly changed compared with pure TiO2. The ER behaviors of the suspensions prepared with TiO2 particles and the DAP modified particles are tested. The results indicate that the DAP modified particle-based ER fluids have a much higher ER efficiency and higher shear stress than the TiO2 particle-based suspension. The highest ER efficiency obtained is 1.2 × 105% at 5 kV mm-1, which is two orders magnitude higher than the TiO2 particle-based suspension.

  5. THE COMPLETE NUCLEAR ESTROGEN RECEPTOR FAMILY IN THE RAINBOW TROUT: DISCOVERY OF THE NOVEL ER.2 AND BOTH ER. ISOFORMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen hormones interact with cellular ERs to exert their biological effects in vertebrate animals. Similar to other animals, fishes have two distinct ER subtypes, ERa (NR3A1) and ERb (NR3A2). The ERb subtype is found as two different isoforms in several fish species because of a gene duplication ...

  6. 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.

  7. 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

  8. 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.

  9. Paliperidone ER: a review of the clinical trial data

    PubMed Central

    Janicak, Philip G; Winans, Elizabeth A

    2007-01-01

    Paliperidone extended-release tablet (paliperidone ER; INVEGA™) is an oral antipsychotic for the treatment of schizophrenia. The recommended dose range is 3–12 mg per day. Paliperidone ER utilizes the OROS® delivery system, which allows for once-daily dosing. Its pharmacokinetic profile results in a more stable serum concentration. Paliperidone is 9-hydroxyrisperidone, the chief active metabolite of risperidone. It undergoes limited hepatic metabolism, thereby minimizing the risks of hepatic drug–drug and drug–disease interactions. Three 6-week trials in patients with acute schizophrenia reported that paliperidone ER was effective, well tolerated, and produced clinically meaningful improvements in personal and social functioning compared with placebo. Post-hoc analysis of these trials in various populations, including recently diagnosed, elderly and more severely ill patients, those with sleep disturbances and those with predominant negative symptoms demonstrated improvement as well. Paliperidone ER was also significantly better than placebo in the prevention of symptom recurrence in a 6-month maintenance study. The most common clinically relevant adverse events associated with paliperidone ER were extrapyramidal symptoms, tachycardia and somnolence. The incidence of Parkinsonism, akathisia and use of anticholinergic medications increased in a dose-related manner. Further, modest QTc interval prolongation was observed but did not produce clinical symptoms. Similar to risperidone, paliperidone ER is associated with increases in serum prolactin levels. Overall, paliperidone ER was effective, well tolerated and provides a new treatment option for patients with schizophrenia. PMID:19300622

  10. New COP1-binding motifs involved in ER retrieval.

    PubMed

    Cosson, P; Lefkir, Y; Démollière, C; Letourneur, F

    1998-12-01

    Coatomer-mediated sorting of proteins is based on the physical interaction between coatomer (COP1) and targeting motifs found in the cytoplasmic domains of membrane proteins. For example, binding of COP1 to dilysine (KKXX) motifs induces specific retrieval of tagged proteins from the Golgi back to the endoplasmic reticulum (ER). Making use of the two-hybrid system, we characterized a new sequence (deltaL) which interacts specifically with the delta-COP subunit of the COP1 complex. Transfer of deltaL to the cytoplasmic domain of a reporter membrane protein resulted in its localization in the ER, in yeast and mammalian cells. This was due to continuous retrieval of tagged proteins from the Golgi back to the ER, in a manner similar to the ER retrieval of KKXX-tagged proteins. Extensive mutagenesis of deltaL identified an aromatic residue as a critical determinant of the interaction with COP1. Similar COP1-binding motifs containing an essential aromatic residue were identified in the cytoplasmic domain of an ER-resident protein, Sec71p, and in an ER retention motif previously characterized in the CD3epsilon chain of the T-cell receptor. These results emphasize the role of the COP1 complex in retrograde Golgi-to-ER transport and highlight its functional similarity with clathrin-adaptor complexes. PMID:9843492

  11. Ammonia synthesis and ER-MCFC-technology - a profitable combination?

    SciTech Connect

    Dijkema, G.P.J.; Vervoort, J.; Daniels, R.J.E.; Luteijn, C.P.

    1996-12-31

    Similar to stand-alone ER-MCFC power systems industrial ammonia production facilities include hydrogen-rich synthesis-gas production. Therefore, integration of ER-MCFC stacks in a conventional industrial ammonia plant was investigated. By preliminary process design calculations three promising process structures were evaluated: (1) ER-MCFC is fed by the ammonia plant`s steam-reformer; anode off-gas to firing (2) similar to structure 1; in this case the anode off-gas is redirected to the ammonia process (3) ER-MCFC is fed by ammonia-synthesis purge gas The results indicate that for options 1 and 3 a return-on-investment for the ER-MCFC of around 8% is achievable at a stack cost of $250/kW and a revenue of 7c/kWh. Option 2 is not profitable, because of the associated reduction in ammonia production. The degree of hydrogen-utilization in the ER-MCFC to be selected for maximum profit varies with the process structure and indicates that there is scope for ER-MCFC stacks which operate at low hydrogen-utilization.

  12. Brain activity during complex imagined gait rasks in Parkinson disease

    PubMed Central

    Peterson, Daniel S.; Pickett, Kristen A.; Duncan, Ryan; Perlmutter, Joel; Earhart, Gammon M.

    2013-01-01

    Objective Motor imagery during functional magnetic resonance imaging (fMRI) allows assessment of brain activity during tasks, like walking, that cannot be completed in a scanner. We used gait imagery to assess the neural pathophysiology of locomotion in Parkinson disease (PD). Methods Brain activity was measured in five locomotor regions (supplementary motor area (SMA), globus pallidus (GP), putamen, mesencephalic locomotor region, cerebellar locomotor region) during simple (forward) and complex (backward, turning) gait imagery. Brain activity was correlated to overground walking velocity. Results Across tasks, PD exhibited reduced activity in the globus pallidus compared to controls. People with PD, but not controls, exhibited more activity in the SMA during imagined turning compared to forward or backward walking. In PD, walking speed was correlated to brain activity in several regions. Conclusions Altered SMA activity in PD during imagined turning may represent compensatory neural adaptations during complex gait. The lowered activity and positive correlation to locomotor function in GP suggests reduced activity in this region may relate to locomotor dysfunction. Significance This study elucidates changes in neural activity during gait in PD, underscoring the importance of testing simple and complex tasks. Results support a positive relationship between activity in locomotor regions and walking ability. PMID:24210997

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Laser cooling of Er3+-doped solids

    NASA Astrophysics Data System (ADS)

    Nemova, Galina; Kashyap, Raman

    2010-10-01

    We consider theoretically a mechanism for laser cooling in rare-earth-doped low-phonon materials based simultaneously on two cooling cycles: a traditional cooling cycle with an anti-Stokes fluorescence transition as well as an infrared-to-visible upconversion cycle, to overcome the self-termination effects in either anti-Stokes or upconversion cooling on its own. Our simulations, performed for erbium-doped potassium-lead chloride crystal ( Er3+:KPl 2Cl 5) known to be an extremely low phonon energy host, uses two pump wavelengths corresponding to the long wavelength tails of the absorption spectra of the 4I15/2 → 4I13/2 and 4I15/2 → 4I9/2 transitions. The contribution of each pump source to the cooling process is comprehensively investigated. We show that, although the energy gap between 4I15/2 and 4I9/2 levels exceeds the energy gap between 4I15/2 and 4I13/2 levels and cooling process is more efficient with the cycle based on the 4I15/2 → 4I13/2 transition, the second cooling cycle based on the 4I15/2 → 4I9/2 transition can be used as a supplementary one.

  19. 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

  20. 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

  1. Er3+ infrared fluorescence affected by spatial distribution synchronicity of Ba2+ and Er3+ in Er3+-doped BaO-SiO2 glasses

    NASA Astrophysics Data System (ADS)

    Masuno, Atsunobu; Inoue, Hiroyuki; Saito, Yoshihiro

    2016-02-01

    Glasses with the composition xBaO-(99.9 - x)SiO2-0.1ErO3/2 (0 ≤x ≤ 34.9) were fabricated by a levitation technique. The glasses in the immiscibility region were opaque due to chemical inhomogeneity, while the other glasses were colorless and transparent. The scanning electron microscope observations and electron probe microanalysis scan profiles revealed that more Er3+ ions were preferentially distributed in the regions where more Ba2+ ions existed in the chemically inhomogeneous glasses. The synchronicity of the spatial distributions of the two ions initially increased with increasing x and then decreased when the Ba2+ concentration exceeded a certain value. The peak shape and lifetime of the fluorescence at 1.55 μm depended on x as well as the spatial distribution of both ions. These results indicate that although ErOn polyhedra are preferentially coordinated with Ba2+ ions and their local structure is affected by the coordination of Ba2+, there is a maximum in the amount of Ba2+ ions that can coordinate ErOn polyhedra since the available space for Ba2+ ions is limited. These findings provide us with efficient ways to design the chemical composition of glasses with superior Er3+ fluorescence properties for optical communication network systems.

  2. 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.

  3. 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.

  4. 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

  5. Wheel slip control of ABS using ER valve pressure modulator

    NASA Astrophysics Data System (ADS)

    Choi, Seung-Bok; Cho, Myung-Soo; Kim, Yong-Il; Choi, Young-Tai; Wereley, Norman M.

    2004-07-01

    This paper presents a wheel slip control via sliding mode controller for a new anti-lock brake system (ABS) of a passenger vehicle using electrorheological (ER) valve pressure modulator. The principal design parameters of the ER valves and hydraulic booster are appropriately determined by considering braking pressure variation during ABS operation. An electrically controllable pressure modulator using the ER valves is then constructed and its governing equations are derived. Subsequently, the pressure control performance of the new pressure modulator is experimentally evaluated. The governing equations of motion for a quarter car wheel model are derived and the sliding mode controller is formulated for wheel slip control. Hardware in the loop simulation (HILS) for braking performance evaluation is undertaken in order to demonstrate the effectiveness of the proposed ABS associated with the ER valve pressure modulator.

  6. The kinetics of ER fusion protein activation in vivo.

    PubMed

    Wilson, C H; Gamper, I; Perfetto, A; Auw, J; Littlewood, T D; Evan, G I

    2014-10-01

    Reversibly switchable proteins are powerful tools with which to explore protein function in vitro and in vivo. For example, the activity of many proteins fused to the hormone-binding domain of the modified oestrogen receptor (ER(TAM)) can be regulated by provision or removal of 4-hydroxytamoxifen (4-OHT). Despite the widespread use of ER(TAM) fusions in vivo, inadequate data are available as to the most efficacious routes for systemic tamoxifen delivery. In this study, we have used two well-characterized ER(TAM) fusion proteins, both reversibly activated by 4-OHT, to compare the effectiveness and kinetics of 4-OHT delivery in mice in vivo by either tamoxifen in food or by intraperitoneal injection. Our data indicate that dietary tamoxifen offers an effective, facile and ethically preferable means for long-term activation of ER(TAM) fusion proteins in vivo. PMID:24662815

  7. 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.

  8. Dynamics of induced dipole ER fluid: a continuous energetic approach

    NASA Astrophysics Data System (ADS)

    Zhang, Jianwei; Li, Wenfeng; Li, Jiaxi

    2011-03-01

    We studied dynamics of Electrorheological (ER) fluid by continuum induced dipole fluid method. We found that the velocity profile of ER fluid increases in high shear-rate region and solid particles are separated from colloid in high electric field. These findings demonstrated the breakdown of Bingham fluid model under high shear-rate and high electric field. Our continuum approach describes ER fluid's behaviors under most conditions. We also found that the shift of maximum shear stress under different electric field follows the same trend as that of the maximum static stress. This indicates that the static and dynamic stresses are both dominated by the same energetic process. A connection between micro-particles' structures and macro-dynamic properties under varying conditions is established by our continuum method. Our studies probe the physics of induced dipole ER fluid.

  9. ER-2 High Altitude Solar Cell Calibration Flights

    NASA Technical Reports Server (NTRS)

    Myers, Matthew G.; Piszczor, Michael F.

    2015-01-01

    The first flights of the ER-2 solar cell calibration demonstration were conducted during September-October of 2014. Three flights were performed that not only tested out the equipment and operational procedures, but also demonstrated the capability of this unique facility by conducting the first short-circuit measurements on a variety of test solar cells. Very preliminary results of these first flights were presented at the 2014 Space Photovoltaic Research and Technology (SPRAT) Conference in Cleveland, OH shortly following these first flights. At the 2015 Space Power Workshop, a more detailed description of these first ER-2 flights will be presented, along with the final flight data from some of the test cells that were flown and has now been reduced and corrected for ER-2 atmospheric flight conditions. Plans for ER-2 flights during the summer of 2015 will also be discussed.

  10. 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

  11. 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

  12. Transitions of protein traffic from cardiac ER to junctional SR.

    PubMed

    Sleiman, Naama H; McFarland, Timothy P; Jones, Larry R; Cala, Steven E

    2015-04-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca(2+) release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQ-DsRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed ((del)TRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and (del)TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic. PMID:25640161

  13. Transitions of protein traffic from cardiac ER to junctional SR

    PubMed Central

    Sleiman, Naama H.; McFarland, Timothy P.; Jones, Larry R.; Cala, Steven E.

    2015-01-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca2+ release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24 h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48 h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQD-sRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed (delTRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and del TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic. PMID:25640161

  14. [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

  15. 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

  16. AFM observation of OMVPE-grown ErP on InP substrates using a new organometal tris(ethylcyclopentadienyl)erbium (Er(EtCp) 3)

    NASA Astrophysics Data System (ADS)

    Akane, T.; Jinno, S.; Yang, Y.; Kuno, T.; Hirata, T.; Isogai, Y.; Watanabe, N.; Fujiwara, Y.; Nakamura, A.; Takeda, Y.

    2003-06-01

    ErP has been grown on InP(0 0 1) substrates by organometallic vapor phase epitaxy (OMVPE) using a new liquid organic Er source: tris(ethylcyclopentadienyl)erbium (Er(EtCp) 3). Morphological change of an ErP layer on InP(0 0 1) is investigated together with that of an overgrown capping InP layer. Optimum growth condition of InP causes islanding on over-monolayer-ErP. A relatively low overgrowth temperature of InP is a key factor for attaining complete capping coverage on ErP.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Herp enhances ER-associated protein degradation by recruiting ubiquilins

    SciTech Connect

    Kim, Tae-Yeon; Kim, Eunmin; Yoon, Sungjoo Kim; Yoon, Jong-Bok

    2008-05-02

    ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3{delta}, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3{delta} was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates.

  2. 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.

  3. A model for the generation and interconversion of ER morphologies

    PubMed Central

    Shemesh, Tom; Klemm, Robin W.; Romano, Fabian B.; Wang, Songyu; Vaughan, Joshua; Zhuang, Xiaowei; Tukachinsky, Hanna; Kozlov, Michael M.; Rapoport, Tom A.

    2014-01-01

    The peripheral endoplasmic reticulum (ER) forms different morphologies composed of tubules and sheets. Proteins such as the reticulons shape the ER by stabilizing the high membrane curvature in cross-sections of tubules and sheet edges. Here, we show that membrane curvature along the edge lines is also critical for ER shaping. We describe a theoretical model that explains virtually all observed ER morphologies. The model is based on two types of curvature-stabilizing proteins that generate either straight or negatively curved edge lines (R- and S-type proteins). Dependent on the concentrations of R- and S-type proteins, membrane morphologies can be generated that consist of tubules, sheets, sheet fenestrations, and sheet stacks with helicoidal connections. We propose that reticulons 4a/b are representatives of R-type proteins that favor tubules and outer edges of sheets. Lunapark is an example of S-type proteins that promote junctions between tubules and sheets. In a tubular ER network, lunapark stabilizes three-way junctions, i.e., small triangular sheets with concave edges. The model agrees with experimental observations and explains how curvature-stabilizing proteins determine ER morphology. PMID:25404289

  4. 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.

  5. 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.

  6. Co- and Post-Translational Protein Folding in the ER.

    PubMed

    Ellgaard, Lars; McCaul, Nicholas; Chatsisvili, Anna; Braakman, Ineke

    2016-06-01

    The biophysical rules that govern folding of small, single-domain proteins in dilute solutions are now quite well understood. The mechanisms underlying co-translational folding of multidomain and membrane-spanning proteins in complex cellular environments are often less clear. The endoplasmic reticulum (ER) produces a plethora of membrane and secretory proteins, which must fold and assemble correctly before ER exit - if these processes fail, misfolded species accumulate in the ER or are degraded. The ER differs from other cellular organelles in terms of the physicochemical environment and the variety of ER-specific protein modifications. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and underline the influence of protein modifications on these processes. We emphasize how method development has helped advance the field by allowing researchers to monitor the progression of folding as it occurs inside living cells, while at the same time probing the intricate relationship between protein modifications during folding. PMID:26947578

  7. Physiological ER Stress Mediates the Differentiation of Fibroblasts.

    PubMed

    Matsuzaki, Shinsuke; Hiratsuka, Toru; 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-β can induce fibroblast differentiation into myofibroblasts, which express α-smooth muscle actin. Well-differentiated myofibroblasts show increased production of collagen and TGF-β, 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 α-smooth muscle actin signals without TGF-β 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

  8. 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.

  9. 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%.

  10. Contact of cis-Golgi with ER exit sites executes cargo capture and delivery from the ER

    PubMed Central

    Kurokawa, Kazuo; Okamoto, Michiyo; Nakano, Akihiko

    2014-01-01

    Protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus is mediated by coat complex II (COPII) vesicles. It has been believed that COPII vesicles containing cargo are released from the ER exit sites (ERES) into the cytosol and then reach and fuse with the first post-ER compartment, cis-Golgi or ER-to-Golgi intermediate compartment (ERGIC). However, it still remains elusive how cargo loading to vesicles, vesicle budding, tethering and fusion are coordinated in vivo. Here we show, using extremely high speed and high resolution confocal microscopy, that the cis-Golgi in the budding yeast Saccharomyces cerevisiae approaches and contacts the ERES. The COPII coat cage then collapses and the cis-Golgi captures cargo. The cis-Golgi, thus loaded with cargo, then leaves the ERES. We propose that this ‘hug-and-kiss’ behaviour of cis-Golgi ensures efficient and targeted cargo transport from the ERES to cis-Golgi. PMID:24728174

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. The Verdet constant of Er-doped crystalline YAG and tellurite glass at 1645 nm

    NASA Astrophysics Data System (ADS)

    Harris, Lachlan; Ottaway, David; Veitch, Peter J.

    2012-02-01

    We describe the measurement of the Verdet constant of undoped and Er-doped crystalline YAG and tellurite glass at 1645 nm. The undoped YAG value is compared to those measured using visible light. We show that the paramagnetic nature of Er reduces the Verdet constant but that the decrease is probably not significant for the typical Er doping levels used in Er:YAG or in Er:tellurite-glass mid-IR lasers.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Excitation mechanisms of Er optical centers GaN epilayers

    NASA Astrophysics Data System (ADS)

    Hawkins, Matthew; Jiang, Hongxing; Lin, Jingyu; Zavada, John; Vinh, Nguyen

    We report direct evidence of two mechanisms responsible for the excitation of optically active Er3 + ions in GaN epilayers grown by metal-organic chemical vapor deposition. These mechanisms, resonant excitation via the higher-lying inner 4f shell transitions and band-to-band excitation of the semiconductor host, lead to narrow emission lines from isolated and the defect-related Er optical centers. However, these centers have different photoluminescence spectra, local defect environments, decay dynamics, and excitation cross sections. The photoluminescence at 1.54 micrometer from the isolated Er optical center which can be excited by either mechanism has the same decay dynamics, but possesses a much higher excitation cross-section under band-to-band excitation. In contrast, the photoluminescence at 1.54 micrometer from the defect-related Er optical center can only be observed through band-to-band excitation but has the largest excitation cross-section. These results explain the difficulty in achieving gain in Er doped GaN and indicate approaches for realization of optical amplification, and possibly lasing, at room temperature.

  3. Hippocampal ER Stress and Learning Deficits Following Repeated Pyrethroid Exposure

    PubMed Central

    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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Control Performance of Vehicle Abs Featuring ER Valve Pressure Modulator

    NASA Astrophysics Data System (ADS)

    Cho, M. S.; Choi, S. B.; Wereley, N. M.

    In this work, an electrically controllable anti-lock brake system (ABS) for passenger vehicle is developed by utilizing electrorheological (ER) fluid. A pressure modulator which consists of a cylindrical ER valve and the hydraulic booster is constructed in order to achieve sufficient brake pressure variation during ABS operation. The principal design parameters of the modulator are determined by considering ER properties as well as required braking pressure. After investigating pressure controllability of the modulator, a vehicle model which is integrated with the proposed pressure modulator is formulated to design yaw rate controller. A sliding mode controller is designed to obtain desired yaw rate, and the friction forces between roads and wheels are estimated via the estimator. Braking performances of the proposed ABS under various roads are evaluated through the hardware-in-the-loop-simulation (HILS) and the steering stability during braking operation is demonstrated by undertaking split-μ test.

  11. Phosphoinositide kinase signaling controls ER-PM cross-talk.

    PubMed

    Omnus, Deike J; Manford, Andrew G; Bader, Jakob M; Emr, Scott D; Stefan, Christopher J

    2016-04-01

    Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in lipid homeostasis are linked to the progression of several diseases. However, little is known about the sensory mechanisms for detecting membrane composition and how lipid metabolism is regulated in response to membrane stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the endoplasmic reticulum (ER) to modulate essential responses, including Ca(2+)-regulated lipid biogenesis, upon plasma membrane (PM) stress. Furthermore, loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Thus PI kinase-mediated ER-PM cross-talk comprises a regulatory system that ensures cellular integrity under membrane stress conditions. PMID:26864629

  12. 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.

  13. Ultra-High Spin Spectroscopy In Er Nuclei

    NASA Astrophysics Data System (ADS)

    Simpson, J.

    2008-11-01

    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 γ 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 45ℏ in the N 90 Er nuclei. These weakly populated rotational structures have characteristics of triaxial strongly-deformed bands. Such structures have been observed in 157,158,160Er, following a series of experiments using the Gammasphere spectrometer. These observations herald a return to collective excitations at spins of about 50 to 65ℏ. This talk reviews the status of the spectroscopy and understanding of the observed structures in these Er and neighbouring nuclei.

  14. 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

  15. 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

  16. 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

  17. Imiquimod induces ER stress and Ca(2+) influx independently of TLR7 and TLR8.

    PubMed

    Nyberg, William A; Espinosa, Alexander

    2016-05-13

    Endoplasmic reticulum (ER) stress is a physiological response to protein overload or misfolded proteins in the ER. Certain anti-cancer drugs, e.g. bortezomib and nelfinavir, induce ER stress implying that this could be a successful therapeutic strategy against several forms of cancer. To find novel ER-stress inducers we screened a panel of natural and synthetic Toll-like receptor (TLR) agonists against human keratinocytes and identified the anti-cancer drug imiquimod (IMQ) as a potent inducer of ER stress. Other TLR7 and TLR8 agonists, including resiquimod and gardiquimod, did not induce ER stress, demonstrating that IMQ induces ER stress independently of TLR7 and TLR8. We further confirmed this by showing that IMQ could still induce ER stress in mouse Tlr7(-/-) cells. IMQ also induced a rapid and transient influx of extracellular Ca(2+) together with the release of Ca(2+) from internal stores. Depletion of Ca(2+) from the ER is a known cause of ER stress suggesting that IMQ induces ER stress via depletion of ER Ca(2+). The ER-stress inducing property of IMQ is possibly of importance for its efficacy in treating basal cell carcinoma, in situ melanoma, and squamous cell carcinoma. Our data could potentially be harnessed for rational design of even more potent ER-stress inducers and new anti-cancer drugs. PMID:27003259

  18. Orchestration of secretory protein folding by ER chaperones

    PubMed Central

    Gidalevitz, Tali; Stevens, Fred; Argon, Yair

    2013-01-01

    The endoplasmic reticulum is a major compartment of protein biogenesis in the cell, dedicated to production of secretory, membrane and organelle proteins. The secretome has distinct structural and post-translational characteristics, since folding in the ER occurs in an environment that is distinct in terms of its ionic composition, dynamics and requirements for quality contol. The folding machinery in the ER therefore includes chaperones and folding enzymes that introduce, monitor and react to disulfide bonds, glycans, and fluctuations of luminal calcium. We describe the major chaperone networks in the lumen and discuss how they have distinct modes of operation that enable cells to accomplish highly efficient production of the secretome. PMID:23507200

  19. Next generation Er:YAG fractional ablative laser

    NASA Astrophysics Data System (ADS)

    Heinrich, A.; Vizhanyo, A.; Krammer, P.; Summer, S.; Gross, S.; Bragagna, T.; Böhler, 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).

  20. 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 μs 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.

  1. 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.

  2. Clinical highlights from the 2011 ERS Congress in Amsterdam

    PubMed Central

    Spruit, Martijn A.; Chavannes, Niels H.; Herth, Felix J.F.; Poletti, Venerino; Ley, Sebastian; Burghuber, Otto C.; Clini, Enrico; Cottin, Vincent

    2012-01-01

    This article reports on selected papers pertinent to the most important clinical problems in the field of respiratory medicine. Expert authors from the Clinical Assembly of the European Respiratory Society (ERS) have selected updated reports related to presentations given at the 2011 ERS Annual Congress, which was held in Amsterdam (the Netherlands) and attended by more than 20,000 participants. The hot topics and selected abstracts from the scientific groups of the Clinical Assembly are discussed here in the context of recent literature. PMID:22408196

  3. 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

  4. 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

  5. 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

  6. 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 (ER–ER) fusion. In Saccharomyces cerevisiae, the dynamin-like GTPase Sey1p can mediate ER–ER fusion, but sey1Δ cells have no growth defect and only slightly perturbed ER structure. Recent work suggested that ER-localized soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) mediate a Sey1p-independent ER–ER fusion pathway. However, an alternative explanation—that the observed phenotypes arose from perturbed vesicle trafficking—could not be ruled out. In this study, we used candidate and synthetic genetic array (SGA) approaches to more fully characterize SNARE-mediated ER–ER fusion. We found that Dsl1 complex mutations in sey1Δ cells cause strong synthetic growth and ER structure defects and delayed ER–ER fusion in vivo, additionally implicating the Dsl1 complex in SNARE-mediated ER–ER fusion. In contrast, cytosolic coat protein I (COPI) vesicle coat mutations in sey1Δ 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 ER–ER fusion pathways caused almost complete inviability. We conclude that the ER SNAREs and the Dsl1 complex directly mediate Sey1p-independent ER–ER fusion and that, in the absence of both pathways, cell viability depends upon membrane curvature–promoting reticulons. PMID:25187651

  7. A Human Estrogen Receptor (ER)α Mutation with Differential Responsiveness to Nonsteroidal Ligands: Novel Approaches for Studying Mechanism of ER Action

    PubMed Central

    Paulmurugan, Ramasamy; Tamrazi, Anobel; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.; Gambhir, Sanjiv S.

    2008-01-01

    Estrogens, acting through the estrogen receptors (ERs), play crucial roles in regulating the function of reproductive and other systems under physiological and pathological conditions. ER activity in regulating target genes is modulated by the binding of both steroidal and synthetic nonsteroidal ligands, with ligand binding inducing ERs to adopt various conformations that control their interactions with transcriptional coregulators. Previously, we developed an intramolecular folding sensor with a mutant form of ERα (ERG521T) that proved to be essentially unresponsive to the endogenous ligand 17β-estradiol, yet responded very well to certain synthetic ligands. In this study, we have characterized this G521T-ER mutation in terms of the potency and efficacy of receptor response toward several steroidal and nonsteroidal ligands in two different ways: directly, by ligand effects on mutant ER conformation (by the split-luciferase complementation system), and indirectly, by ligand effects on mutant ER transactivation. Full-length G521T-ER shows no affinity for estradiol and does not activate an estrogen-responsive reporter gene. The synthetic pyrazole agonist ligand propyl-pyrazole-triol is approximately 100-fold more potent than estradiol in inducing intramolecular folding and reporter gene transactivation with the mutant ER, whereas both ligands have high potency on wild-type ER. This estradiol-unresponsive mutant ER can also specifically highlight the agonistic property of the selective ER modulator, 4-hydroxytamoxifen, by reporter gene transactivation, even in the presence of estradiol, and it can exert a dominant-negative effect on estrogen-stimulated wild-type ER. This system provides a model for ER-mutants that show differential ligand responsiveness to gene activation to gain insight into the phenomenon of hormone resistance observed in endocrine therapies of ER-positive breast cancers. PMID:18451095

  8. Fluoride glass fiber for reliable Er:YAG and Er,Cr:YSGG laser power delivery

    NASA Astrophysics Data System (ADS)

    Séguin, François; Saad, Mohammed; Orsini, Patrick; Baierl, Dieter

    2008-02-01

    Compared to other transparent infrared fiber materials, ZBLAN fluoride glasses promise to be best suited for laser power delivery in the 3μm wavelength region due to their high transmission and excellent mechanical flexibility. These claims were demonstrated in a series of power handling tests of both straight and coiled fibers using an Er,Cr:YSGG laser emitting a train of pulses of 150 μs duration at a repetition frequency of 20 Hz producing 7.5 W average power. Large core fibers (450/510μm 0,2NA) are characterized by an attenuation of 0.02dB/m at 3μm and stay within 0.5°C from ambient temperature when carrying full laser power. A 2-m fiber length prepared with bare cleaves has been tested for over 23 hours, cumulating 1,140,000 shots of 1530 J/cm2 fluence while maintaining 90% transmission without any measurable degradation. Coiling the fiber to 11 cm radius did not have an impact on power handling reliability. These results show the potential of these highly transparent fibers in surgical laser delivery applications.

  9. 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.

  10. 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

  11. 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

  12. Mitochondria-associated ER membranes in Alzheimer disease.

    PubMed

    Schon, Eric A; Area-Gomez, Estela

    2013-07-01

    Alzheimer disease (AD) is associated with the accumulation in the brain of extracellular neuritic plaques composed mainly of β-amyloid (Aβ) and of intracellular neurofibrillary tangles composed of hyperphosphorylated forms of the microtubule-associated protein tau. It is also associated with other features that have received less attention, including aberrant phospholipid, cholesterol, and calcium metabolism, and altered mitochondrial function and dynamics. The underlying mechanism(s) that might explain these observations are currently unknown. We recently showed that presenilin-1 (PS1), presenilin-2 (PS2), and γ-secretase activity, which processes the amyloid precursor protein (APP) to generate Aβ, are located predominantly in a specialized subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM). MAM is an intracellular lipid raft-like structure intimately involved in cholesterol and phospholipid lipid metabolism, in calcium homeostasis, and in mitochondrial function and dynamics. The coincidence of the functions associated with MAM with the symptomatology of AD led us to speculate that presenilins play a role in maintaining MAM function. We found that, consistent with this supposition, both MAM function and ER-mitochondrial connectivity are increased significantly in AD, which may help explain many of the biochemical and morphological features of the disease. Based on these findings, we propose that AD is fundamentally a disorder of ER-mitochondrial communication (the "MAM hypothesis"). This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. PMID:22922446

  13. Personality and Conjugal Bereavement in Older Widow(er)s.

    ERIC Educational Resources Information Center

    Meuser, Thomas M.

    1995-01-01

    Examines the degree to which an individual's propensity to experience emotional distress and restraint are predictive of grief intensity in a sample of older widow(er)s (n=51). Characteristic distress was found to be a significant predictor of present grief intensity, whereas repressive defensiveness was found to predict past grief, as recalled…

  14. Resonantly pumped continuous wave Er:YAP laser

    NASA Astrophysics Data System (ADS)

    Yao, B. Q.; Liu, X. L.; Yu, L. X.; Sun, X. H.; Chen, Z. Y.; Wang, Y. Z.

    2012-04-01

    A continuous wave Er:YAP laser pumped by Mgo:PPLN laser locked at 1535 nm was reported. 170 mW of 1609 nm output was achieved under total incident pump power of 7 W at 77 K. The slope efficiency were 5.0 and 3.1% with the cavity length 75 and 140 mm.

  15. Resonantly pumped multiwavelength operation in Er:YAP

    NASA Astrophysics Data System (ADS)

    Yao, B. Q.; Liu, X. L.; Yu, L. X.; Sun, X. H.; Chen, Z. Y.; Wang, Y. Z.

    2012-05-01

    A multiwavelength Er:YAP laser pumped by MgO:PPLN locked at 1535 nm with etalon was reported. 170 mW of 1609 nm, 120 mW of 1623 nm output were achieved under total incident pump power of 7 W at 77 K. The slope efficiency were 5.5, 7.2% of the two wavelength.

  16. 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.

  17. School Officials and the Courts: Update 1984. ERS Monograph.

    ERIC Educational Resources Information Center

    Beckham, Joseph C.

    This is the seventh in a series of Educational Research Service (ERS) monographs designed to summarize judicial decisions on elementary and secondary education issues by state and federal courts. These cases, dating from June 30, 1983 to June 30, 1984, were selected on the basis of their relevance to contemporary problems in public schools, their…

  18. Er:YAG laser dentistry in special needs patients

    PubMed Central

    Fornaini, Carlo; Clini, Fabio; Fontana, Matteo; Cella, Luigi; Oppici, Aldo

    2015-01-01

    Objective: Between a quarter and a third of adults with intellectual disability is estimated to have dental anxiety. Unpleasant stimuli, such as the injection of local anaesthesia or the noise and vibration of rotary instruments, may provoke anxiety and subsequent low compliance until the opposition to the treatment. The use of Er:YAG laser in conservative dentistry had a great development in these last years thank to new devices and also to their advantages when compared to the conventional instruments. The aim of this clinical study was to show the advantages of the Er:YAG laser in the conservative treatment of Special Care patients. Methods: Four cases are here described to show the Er:YAG laser use in our Unit on special needs patients. Results and conclusions: Based on the experience gained on conservative laser-assisted treatments performed in a time of 5 years at our Dentistry, Special Needs and Maxillo-Facial Surgery Unit we may affirm that Er:YAG laser may be considered as a good way to improve the cooperation, to reduce anxiety related to rotating instruments and to reach better results with equal or shorter operating times. PMID:26557733

  19. 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…

  20. 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.

  1. 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

  2. Mesoscale wind measurements using recalibrated ERS SAR images

    NASA Astrophysics Data System (ADS)

    Lehner, S.; Horstmann, J.; Koch, W.; Rosenthal, W.

    1998-04-01

    The precision images (PRI) of the synthetic aperture radars (SAR) on board the European Remote Sensing Satellites ERS-1 and ERS-2 are used to derive mesoscale wind fields over the ocean. For calculation of the wind speed the C-band model (CMOD4) is used, which was originally developed by Stoffelen and Anderson [1993] for the European Space Agency (ESA) to derive wind fields from measurements of the wind scatterometer (SCAT). In the case of the ERS-1/2 SAR the CMOD4 is used to compute the wind speed from the normalized radar backscatter cross section (NRCS) and the incidence angle of the radar beam, both computed from the SAR.PRI data. The third input variable is the wind direction, which is estimated from the wind streaks in the images or from ground truth measurements. The SAR data are affected by a power loss, caused by saturation of the analog to digital converter (ADC) of the SAR. Therefore the images have to be recalibrated. Errors in the derived wind speed are mainly due to ADC saturation and uncertainties of the input wind direction. These errors are estimated for various wind conditions. Mesoscale wind fields computed from ERS-1/2 SAR.PRI images taken between the Shetland Islands and the west coast of Norway are compared to ground truth measurements and modeled wind fields from the German weather service (DWD). Wind fields of the nonhydrostatic mesoscale model Geesthacht simulation model of the atmosphere (GESIMA) are compared to the derived wind field of the ERS-1 SAR.PRI image at the island Rügen in the Baltic Sea.

  3. 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.

  4. 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.

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

    MedlinePLUS

    ... in the ER, Especially Young Males Synthetic Marijuana Lands Thousands of Young People in the ER, Especially ... reduced in severe marijuana dependence ( March 2016 ) Substance use disorders extremely common among previously incarcerated youth ( March ...

  6. 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 ...

  7. 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

  8. Activating transcription factor 4, an ER stress mediator, is required for, but excessive ER stress suppresses osteoblastogenesis by bortezomib.

    PubMed

    Nakamura, Shingen; Miki, Hirokazu; Kido, Shinsuke; Nakano, Ayako; Hiasa, Masahiro; Oda, Asuka; Amou, Hiroe; Watanabe, Keiichiro; Harada, Takeshi; Fujii, Shiro; Takeuchi, Kyoko; Kagawa, Kumiko; Ozaki, Shuji; Matsumoto, Toshio; Abe, Masahiro

    2013-07-01

    Endoplasmic reticulum (ER) stress is induced in matrix-producing osteoblasts and plays an essential role in osteoblastogenesis. Although the bone anabolic activity of proteasome inhibitors has been demonstrated, the roles of ER stress induced by proteasome inhibition in osteoblastogenesis remain largely unknown. Here we show that bortezomib translationally increases protein levels of activating transcription factor 4 (ATF4), a downstream mediator of ER stress, in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells. The suppression of ATF4 expression by siRNA abrogated osteocalcin expression and mineralized nodule formation by MC3T3-E1 cells induced by bortezomib, indicating a critical role for ATF4 in bortezomib-mediated osteoblastogenesis. However, bortezomib at 20 nM or higher abolished the mineralized nodule formation along with reductions in the expression of osteoblastogenesis mediators β-catenin and Osterix. Furthermore, at 50 nM, bortezomib induced the expression of C/EBP homologous protein (CHOP), suggesting activation of the ATF4-CHOP pro-apoptotic pathway. These results suggest that a low dose of bortezomib induces osteogenic activity, but that, in contrast, excessive ER stress caused by bortezomib at higher doses hampers osteoblastogenesis. Therefore, dosing schedules for proteasome inhibitors warrant further study to maximize anabolic actions without compromising anti-MM activity in patients with multiple myeloma (MM). PMID:23708974

  9. Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin.

    PubMed

    Lin, Cheng-Tao; Chang, Ting-Chang; Chao, Angel; Dzeng, Elizabeth; Soong, Yung-Kuei; Hung, Chien-Fu; Lai, Chyong-Huey

    2005-01-01

    DNA vaccines have emerged as an attractive approach for generating antigen-specific immunotherapy. Strategies that enhance antigen presentation may potentially be used to enhance DNA vaccine potency. Previous experiments showed that chimeric DNA vaccines utilizing endoplasmic reticulum (ER) chaperone molecules, such as Calreticulin (CRT), linked to an antigen were capable of generating antigen-specific CD8+ T cell immune responses in vaccinated mice. In this study, we tested DNA vaccines encoding the ER chaperone molecules ER-60, tapasin (Tap), or calnexin (Cal), linked to human papillomavirus type 16 (HPV-16) E7 for their abilities to generate E7-specific T cell-mediated immune responses and antitumor effects in vaccinated mice. Our results demonstrated that vaccination with DNA encoding any of these chaperone molecules linked to E7 led to a significant increase in the frequency of E7-specific CD8+ T cell precursors and generated stronger antitumor effects against an E7-expressing tumor in vaccinated mice compared to vaccination with wild-type E7 DNA. Our data suggest that DNA vaccines employing these ER chaperone molecules linked to antigen may enhance antigen-specific CD8+ T cell immune responses, resulting in a significantly more potent DNA vaccine. PMID:15918000

  10. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

    PubMed Central

    Das, Indrajit; Png, Chin Wen; Oancea, Iulia; Hasnain, Sumaira Z.; Lourie, Rohan; Proctor, Martina; Eri, Rajaraman D.; Sheng, Yong; Crane, Denis I.; Florin, Timothy H.

    2013-01-01

    Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX’s suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER. PMID:23650437

  11. ER-luminal thiol/selenol-mediated regulation of Ca2+ signalling.

    PubMed

    Appenzeller-Herzog, Christian; Simmen, Thomas

    2016-04-15

    The endoplasmic reticulum (ER) is the main cellular Ca(2+)storage unit. Among other signalling outputs, the ER can release Ca(2+)ions, which can, for instance, communicate the status of ER protein folding to the cytosol and to other organelles, in particular the mitochondria. As a consequence, ER Ca(2+)flux can alter the apposition of the ER with mitochondria, influence mitochondrial ATP production or trigger apoptosis. All aspects of ER Ca(2+)flux have emerged as processes that are intimately controlled by intracellular redox conditions. In this review, we focus on ER-luminal redox-driven regulation of Ca(2+)flux. This involves the direct reduction of disulfides within ER Ca(2+)handling proteins themselves, but also the regulated interaction of ER chaperones and oxidoreductases such as calnexin or ERp57 with them. Well-characterized examples are the activating interactions of Ero1α with inositol 1,4,5-trisphosphate receptors (IP3Rs) or of selenoprotein N (SEPN1) with sarco/endoplasmic reticulum Ca(2+)transport ATPase 2 (SERCA2). The future discovery of novel ER-luminal modulators of Ca(2+)handling proteins is likely. Based on the currently available information, we describe how the variable ER redox conditions govern Ca(2+)flux from the ER. PMID:27068954

  12. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 relationship... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Relationship as remarried widow(er)....

  13. 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....

  14. 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...

  15. 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

  16. 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

  17. 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

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

    PubMed Central

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

    2016-01-01

    The endoplasmic reticulum (ER) is an essential organelle for cellular metabolic homeostasis including folding and maturation of secretory and membrane proteins. Disruption of ER proteostasis has been implicated in the pathogenesis of various diseases such as diabetes and neurodegenerative diseases. The ER redox state, which is an oxidative environment suitable for disulfide-bond formation, is essential for ER protein quality control. Hence, detection of the ER redox state, especially in living cells, is essential to understand the mechanism by which the redox state of the ER is maintained. However, methods to detect the redox state of the ER have not been well-established because of inefficient folding and stability of roGFP variants with oxidative redox potential like roGFP-iL. Here we have improved the folding efficiency of ER-targeted roGFP-iL (ERroGFP-iL) in cells by introducing superfolder GFP (sfGFP) mutations. Four specific amino acid substitutions (S30R, Y39N, T105N and I171V) greatly improved folding efficiency in Escherichia coli and in the ER of HeLa cells, as well as the thermostability of the purified proteins. Introduction of these mutations also enhanced the dynamic range for redox change both in vitro and in the ER of living cells. ER-targeted roGFP-S4 (ERroGFP-S4) possessing these four mutations could detect physiological redox changes within the ER. ERroGFP-S4 is therefore a novel probe suitable for monitoring redox change in the ER. ERroGFP-S4 can be applied to detect aberrant ER redox states associated with various pathological conditions and to identify the mechanisms used to maintain the redox state of the ER. PMID:26934978

  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. 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.

  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. 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

  4. Wet versus dry enamel ablation by Er:YAG laser.

    PubMed

    Burkes, E J; Hoke, J; Gomes, E; Wolbarsht, M

    1992-06-01

    The purpose of this study was to observe tooth structure and pulpal temperature changes in extracted human teeth subjected to a pulsed Er:YAG (2.94 microns) laser. Two teeth were irradiated while dry and three teeth while moistened by a fine water mist. When the dry teeth were irradiated, there was minimal enamel ablation. SEM of the resulting surface showed rounded fragments of enamel rods, enamel melting, cracks, and smooth-edged voids. Intrapulpal temperature measured by thermal sensor rose more than 27 degrees C. When the laser application on the teeth was pulsed with a constant fine water mist, enamel and dentin were efficiently ablated. SEM of the resulting surfaces showed fissures and conical craters with sharp enamel projections remaining. Intrapulpal temperatures rose an average of 4 degrees C. These results indicate that pulsed Er:YAG (2.94 microns) used with a water mist removes enamel and dentin without producing significant pulpal temperature changes. PMID:1403876

  5. Calibration of the ER-2 meteorological measurement system

    NASA Technical Reports Server (NTRS)

    Bowen, Stuart W.; Chan, K. Roland; Bui, T. Paul

    1991-01-01

    The Meteorological Measurement System (MMS) on the high altitude ER-2 aircraft was developed specifically for atmospheric research. The MMS provides accurate measurements of pressure, temperature, wind vector, position (longitude, latitude, altitude), pitch, roll, heading, angle of attack, angle of sideslip, true airspeed, aircraft eastward velocity, northward velocity, vertical acceleration, and time, at a sample rate of 5/s. MMS data products are presented in the form of either 5 or 1 Hz time series. The 1 Hz data stream, generally used by ER-2 investigators, is obtained from the 5 Hz data stream by filtering and desampling. The method of measurement of the meteorological parameters is given and the results of their analyses are discussed.

  6. Applications of the ER-2 meteorological measurement system

    NASA Technical Reports Server (NTRS)

    Chan, K. Roland; Pfister, Leonhard; Bui, T. Paul; Bowen, Stuart W.; Dean-Day, Jonathan

    1991-01-01

    The NASA ER-2 aircraft is used as a platform for high altitude atmospheric missions. The Meteorological Measurement System (MMS) was developed specifically for atmospheric research to provide accurate high resolution measurements of pressure, temperature, and the 3-D wind vector with a sampling rate of 5/s. The MMS consist of three subsystems: (1) an air motion sensing system to measure the velocity of the air with respect to the aircraft; (2) a high resolution inertial navigation system (INS) to measure the velocity of the aircraft with respect to the earth; and (3) a data acquisition system to sample, process, and record the measurement quantities. MMS data have been used extensively by ER-2 investigators in elucidating the polar ozone chemistry. Herein, applications on atmospheric dynamics are emphasized. Large scale (polar vortex, potential vorticity, model atmosphere), mesoscale (gravity waves, mountain waves) and microscale (heat fluxes) atmospheric phenomena are investigated and discussed.

  7. 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.

  8. Completion report for well ER-30-1

    SciTech Connect

    1995-12-01

    Well ER-30-1 was drilled for the U.S. Department of Energy (DOE), Nevada Operations Office, in support of the Nevada Environmental Restoration Project at the Nevada Test Site (NTS). 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 and the Underground Test Area Operable Unit Project Management Plan. The Well ER-30-1 investigation is part of the DOE`s Underground Test Area (UGTA) Project at the NTS, the goals of which include collecting geological, geophysical, hydrological, and water-chemistry data from new and existing wells to define groundwater migration pathways, rates of migration, and groundwater quality at the NTS. The well will become part of the UGTA monitoring well network.

  9. 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.

  10. 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.

  11. Er-doped planar waveguides for power amplifier applications

    NASA Astrophysics Data System (ADS)

    Mackenzie, J. I.; Murugan, G. S.; Yu, A. W.; Abshire, J. B.

    2013-03-01

    New devices are required to provide effective tools for DIAL or LIDAR measurements from space, which will enable improved mapping of the concentration and distribution of CO2 in our atmosphere. Here we present characteristics of Er-doped thin film waveguides, with an extended gain bandwidth, which are applicable to planar waveguide power amplifiers for wavelengths around the 1572 nm CO2 absorption peaks. Planar waveguide films have been fabricated by sputtering of fluorophosphate and tellurite based glasses onto oxidised silicon wafers, and their properties characterized. The deposition parameters for undoped and Er,Yb-doped films have been assessed and studied, achieving losses of <1.5 dB/cm at 633 nm for the as deposited waveguides. A comparison between the two host materials is made and the potential performance discussed.

  12. Correlation of ER stress and retinal degeneration in tubby mice.

    PubMed

    Cai, Xue; Chen, Lijuan; McGinnis, James F

    2015-11-01

    Mutation of the Tub gene results in the mislocalization of photoreceptor-specific proteins and eventually retinal degeneration. However, the exact mechanism underlying the retinal degeneration remains largely unknown. In this study, we discovered that the expression of endoplasmic reticulum (ER) stress markers, IRE1, ATF6, eIF2α, GRP78/BiP, and XBP-1, is up regulated during tubby retinal development. The dynamics of the expression of these genes are time-dependent and coincided with the time-course of photoreceptor death. Our data also demonstrated that ER stress triggers apoptosis via down-regulation of Bcl2, up-regulation of CHOP and the activation of NF-кB signaling. PMID:26325328

  13. Intracellular zinc distribution in mitochondria, ER and the Golgi apparatus

    PubMed Central

    Lu, Qiping; Haragopal, Hariprakash; Slepchenko, Kira G; Stork, Christian; Li, Yang V

    2016-01-01

    Zinc (Zn2+) is required for numerous cellular functions. As such, the homeostasis and distribution of intracellular zinc can influence cellular metabolism and signaling. However, the exact distribution of free zinc within live cells remains elusive. Previously we showed the release of zinc from thapsigargin/IP3-sensitive endoplasmic reticulum (ER) storage in cortical neurons. In the present study, we investigated if other cellular organelles also contain free chelatable zinc and function as organelle storage for zinc. To identify free zinc within the organelles, live cells were co-stained with Zinpyr-1, a zinc fluorescent dye, and organelle-specific fluorescent dyes (MitoFluor Red 589: mitochondria; ER Tracker Red: endoplasmic reticulum; BODIPY TR ceramide: Golgi apparatus; Syto Red 64: nucleus). We examined organelles that represent potential storing sites for intracellular zinc. We showed that zinc fluorescence staining was co-localized with MitoFluor Red 589, ER Tracker Red, and BODIPY TR ceramide respectively, suggesting the presence of free zinc in mitochondria, endoplasmic reticulum, and the Golgi apparatus. On the other hand, cytosol and nucleus had nearly no detectable zinc fluorescence. It is known that nucleus contains high amount of zinc binding proteins that have high zinc binding affinity. The absence of zinc fluorescence suggests that there is little free zinc in these two regions. It also indicates that the zinc fluorescence detected in mitochondria, ER and Golgi apparatus represents free chelatable zinc. Taken together, our results support that these organelles are potential zinc storing organelles during cellular zinc homeostasis. PMID:27186321

  14. Slow and fast high-spin sequences in 158Er

    NASA Astrophysics Data System (ADS)

    Tjøm, P. O.; Diamond, R. M.; Bacelar, J. C.; Beck, E. M.; Deleplanque, M. A.; Draper, J. E.; Stephens, F. S.

    1985-11-01

    Two branches are observed feeding the 38+ level of the yrast line in 158Er. Two ~1.2-MeV cascade transitions constitute a fast (<1 ps) collective component, probably with only minor changes in shape and structure from those at lower spin. Four slower γ rays (>2 ps) suggest a transition to a different shape and structure, most likely to an oblate 46+ state with all valence particles maximally aligned, a band termination.

  15. 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.

  16. Search for two-phonon vibrations in /sup 168/Er

    SciTech Connect

    Kleppinger, E.W.; Yates, S.W.

    1983-08-01

    The low-lying level structure of /sup 168/Er has been examined by the (n,n'..gamma..) reaction and all known levels with J<7 and E/sub x/< or =2.0 MeV are observed. The discovery of a level at 1893 keV calls for a reexamination of the completeness of the level scheme assumed previously for this nucleus. No new low-lying candidates for two-phonon ..gamma.. vibrations are observed.

  17. Post examination of copper ER sensors exposed to bentonite

    NASA Astrophysics Data System (ADS)

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

    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 μm/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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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 µM 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

  3. 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.

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

    DOEpatents

    Hamilton, Charles E.; Furu, Laurence H.

    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-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.

  7. 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

  8. 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

  9. Er + medium energy ion implantation into lithium niobate

    NASA Astrophysics Data System (ADS)

    Svecova, B.; Nekvindova, P.; Mackova, A.; Oswald, J.; Vacik, J.; Grötzschel, R.; Spirkova, J.

    2009-05-01

    Erbium-doped lithium niobate (Er:LiNbO3) is a prospective photonics component, operating at 1.5 μm, which could find its use chiefly as an optical amplifier or waveguide laser. In this study, we have focused on the properties of the optically active Er:LiNbO3 layers, which are fabricated by medium energy ion implantation under various experimental conditions. Erbium ions were implanted at energies of 330 and 500 keV with fluences of 1.0 × 1015, 2.5 × 1015 and 1.0 × 1016 cm-2 into LiNbO3 single-crystalline cuts of various orientations. The as-implanted samples were annealed in air at 350 °C for 5 h. The depth distribution and diffusion profiles of the implanted Er were measured by Rutherford Backscattering Spectroscopy (RBS) using 2 MeV He+ ions. The projected range RP and projected range straggling ΔRP were calculated employing the SRIM code. The damage distribution and structural changes were described using the RBS/channelling method. Changes of the lithium concentration depth distribution were studied by Neutron Depth Profiling (NDP). The photoluminescence spectra of the samples were measured to determine whether the emission was in the desired region of 1.5 μm. The obtained data made it possible to reveal the relations between the structural changes of erbium-implanted lithium niobate and its luminescence properties important for photonics applications.

  10. 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

  11. Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition.

    PubMed

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

    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 α (ER α ) 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 α protein levels, thereby suppressing ER α transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ER α and increased ER α ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ER α dissociation and ER α ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ER α degradation. Although emodin might induce cytosolic ER α degradation, it primarily affected nuclear ER α 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 α protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future. PMID:23864887

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

    PubMed Central

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

    2009-01-01

    Summary Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca2+ leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity. PMID:18946027

  13. 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

  14. 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

  15. Vesicle-associated membrane protein 7 is expressed in intestinal ER.

    PubMed

    Siddiqi, Shadab A; Mahan, James; Siddiqi, Shahzad; Gorelick, Fred S; Mansbach, Charles M

    2006-03-01

    Intestinal dietary triacylglycerol absorption is a multi-step process. Triacylglycerol exit from the endoplasmic reticulum (ER) is the rate-limiting step in the progress of the lipid from its apical absorption to its basolateral membrane export. Triacylglycerol is transported from the ER to the cis Golgi in a specialized vesicle, the pre-chylomicron transport vesicle (PCTV). The vesicle-associated membrane protein 7 (VAMP7) was found to be more concentrated on PCTVs compared with ER membranes. VAMP7 has been previously identified associated with post-Golgi sites in eukaryotes. To examine the potential role of VAMP7 in PCTV trafficking, antibodies were generated that identified a 25 kDa band consistent with VAMP7 but did not crossreact with VAMP1,2. VAMP7 was concentrated on intestinal ER by immunofluorescence microscopy. Immunoelectron microscopy showed that the ER proteins Sar1 and rBet1 were present on PCTVs and colocalized with VAMP7. Iodixanol gradient centrifugation showed VAMP7 to be isodense with ER and endosomes. Although VAMP7 localized to intestinal ER, it was not present in the ER of liver and kidney. Anti-VAMP7 antibodies reduced the transfer of triacylglycerol, but not newly synthesized proteins, from the ER to the Golgi by 85%. We conclude that VAMP7 is enriched in intestinal ER and that it plays a functional role in the delivery of triacylglycerol from the ER to the Golgi. PMID:16495485

  16. 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

  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. 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.

  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. 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

  1. 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 1,250°C. 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

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

    PubMed

    Agaisse, Hervé; Derré, 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 Sec61ß, 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. 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.

  4. 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 (μTBS) 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 μTBS 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 (α = 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 < 0.05). The surface treatment with Er,Cr:YSGG laser irradiation (4.5 J/cm(2)/50 mJ/30 Hz/140 μs) prior to bonding with a self-etching adhesive system significantly increases adhesion to eroded dentin, as compared to conventional treatment. PMID:23649611

  5. Room temperature continuous-wave laser performance of LD pumped Er:Lu₂O₃ and Er:Y₂O₃ ceramic at 2.7 μm.

    PubMed

    Wang, Li; Huang, Haitao; Shen, Deyuan; Zhang, Jian; Chen, Hao; Wang, Yong; Liu, Xuan; Tang, Dingyuan

    2014-08-11

    We report the demonstration of continue wave operation of diode end-pumped Er:Y2O3 and Er:Lu2O3 ceramic lasers operating at 2.7 μm at room temperature. The maximum output power of 320 mW and 611 mW was obtained from the Er:Y2O3 and Er:Lu2O3 ceramic lasers, with slope efficiency of 6.5% and 7.6%, respectively. Characteristics of Red-shift in lasing wavelength of the ceramic lasers was investigated and discussed. The study indicates that under 967 nm and 976 nm LD pumping, 15 at.% Er-doped Lu2O3 ceramic exhibit a better performance than that of Y2O3 at room temperature. PMID:25321032

  6. 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

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

    PubMed

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

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

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

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. 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

  11. (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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Down conversion of Er3+-Yb3+ couple in Y2BaZnO5

    NASA Astrophysics Data System (ADS)

    Xia, Wenbin; Jin, Xiangliang; Yang, Xiaoliang; Xiao, Siguo

    2016-04-01

    Er3+-Yb3+ co-doped Y2BaZnO5 phosphors were synthesized via high temperature solid-state reaction method. The quantum cutting properties for Er3+-Yb3+ co-doped Y2BaZnO5 phosphors have been detailedly exploited under different wavelength excitation. Unlike in fluoride host, only the Er(4S3/2) + Yb(2F7/2) → Er(4I13/2) + Yb(2F5/2) energy transfer process in Y2BaZnO5 effectively performs the down-conversion, which can split an absorbed high-energy photon into two photons of 1000 nm and 1550 nm radiations. The quantum cutting properties of Er3+-Yb3+ couple in Y2BaZnO5 provides meaningful reference in search of new efficient Er3+-Yb3+ co-doped quantum cutting phosphors.

  19. Effect of OH - on upconversion luminescence of Er 3+-doped oxyhalide tellurite glasses

    NASA Astrophysics Data System (ADS)

    Xu, Shiqing; Fang, Dawei; Zhang, Zaixuan; Jiang, Zhonghong

    2005-06-01

    The Raman spectra, infrared spectra and upconversion luminescence spectra were studied, and the effect mechanism of OH - groups on the upconversion luminescence of Er 3+-doped oxyhalide tellurite glasses was analyzed. The results show that the phonon energy of lead chloride tellurite (PCT) glass was lower than that of lead fluoride tellurite (PFT) glass, but upconversion luminescence intensity of Er 3+-doped PFT glass was higher than that of Er 3+-doped PCT glass. The analysis considers that it was attributed mainly to the effect of OH - groups. The lower the absorption coefficient of the OH - groups, the higher the fluorescence lifetime of Er 3+, and as a result the higher upconversion luminescence intensity of Er 3+. In this work, the effect of OH - groups on the upconversion luminescence of Er 3+ was bigger than that of the phonon energy.

  20. A conserved family of proteins facilitates nascent lipid droplet budding from the ER

    PubMed Central

    Choudhary, Vineet; Ojha, Namrata; Golden, Andy

    2015-01-01

    Lipid droplets (LDs) are found in all cells and play critical roles in lipid metabolism. De novo LD biogenesis occurs in the endoplasmic reticulum (ER) but is not well understood. We imaged early stages of LD biogenesis using electron microscopy and found that nascent LDs form lens-like structures that are in the ER membrane, raising the question of how these nascent LDs bud from the ER as they grow. We found that a conserved family of proteins, fat storage-inducing transmembrane (FIT) proteins, is required for proper budding of LDs from the ER. Elimination or reduction of FIT proteins in yeast and higher eukaryotes causes LDs to remain in the ER membrane. Deletion of the single FIT protein in Caenorhabditis elegans is lethal, suggesting that LD budding is an essential process in this organism. Our findings indicated that FIT proteins are necessary to promote budding of nascent LDs from the ER. PMID:26504167

  1. 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.

  2. 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.

  3. Optical characterization of Er-doped ZnSe for scintillation applications

    NASA Astrophysics Data System (ADS)

    Nasieka, Iu.; Boyko, M.; Strelchuk, V.; Kovalenko, N.; Gerasimenko, A.; Starzhinskiy, N.; Zhukov, A.; Zenya, I.; Sofronov, D.

    2014-12-01

    The effect of Er-doping of ZnSe crystals on luminescence and structural properties was investigated using low-temperature photoluminescence, X-ray luminescence, Raman and IR spectroscopies. It was found that Er dopant atoms with the concentration in the solid phase of about 10-3 wt.% lead to a substantial disordering of initial crystalline structure. The mentioned processes manifest in substantial decrease of the amplitudes of corresponding vibrational modes and increase of their FWHM in first-order Raman spectra of Er-doped ZnSe crystals. Also, Er-doping stimulates an appearance of additional absorbance bands in IR transmittance spectra. However, Er-doping leads to substantial increase of the efficiency of photoluminescence and X-ray luminescence that is very important for scintillation application. In this case, the luminescence is mainly caused by recombination via defect centers which contain Er atoms incorporated in the ZnSe lattice in different electronic configurations.

  4. Ion beam mixing in binary amorphous metallic alloys. [Cu-Er; Ni-Ti

    SciTech Connect

    Hahn, H.; Averback, R.S.; Diaz de la Rubia, T.; Okamoto, P.R.

    1985-12-01

    Ion beam mixing (IM) was measured in homogeneous amorphous metallic alloys of Cu-Er and Ni-Ti as a function of temperature using tracer impurities, i.e., the so-called ''marker geometry''. In Cu-Er, a strong temperature dependence in IM was observed between 80 and 373K, indicating that radiation-enhanced diffusion mechanisms are operative in this metallic glass. Phase separation of the Cu-Er alloy was also observed under irradiation as Er segregated to the vacuum and SiO2 interfaces of the specimen. At low-temperatures, the amount of mixing in amorphous Ni-Ti is similar to that in pure Ni or Ti, but it is much greater in Cu-Er than in either Cu or Er.

  5. T lymphocytes in rat germinal centres belong to an ER3+ subpopulation of CD4+ cells.

    PubMed Central

    Vonderheide, R H; Hunt, S V

    1990-01-01

    Two-colour immunofluorescence histochemistry showed directly that greater than 90% of CD4+ germinal centre T cells in rat spleen or lymph node examined 7 days after immunization bear the antigen recognized by the monoclonal antibody (mAb) ER3. By contrast, only 30-40% of all thoracic duct or lymph node CD4+ cells were ER3+, as determined by two-colour flow cytometry. CD8+ cells were ER3+, but nearly all B cells were ER3-. Thus, germinal centre T cells belong to a subpopulation of CD4+ cells. Because only 25-30% of CD4+ cells that lack higher molecular weight forms of CD45 (i.e. mAb MRC OX32 cells, equivalent to MRC OX22 cells) express ER3, the CD4+ subpopulations defined by ER3 are neither identical nor complementary to the subsets defined by restricted expression of CD45 epitopes. Images Figure 1 PMID:1970805

  6. 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

  7. An ab initio-based Er–He 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.

  8. 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.

  9. Gingival tissue healing following Er:YAG laser ablation compared to electrosurgery in rats.

    PubMed

    Sawabe, Masanori; Aoki, Akira; Komaki, Motohiro; Iwasaki, Kengo; Ogita, Mayumi; Izumi, Yuichi

    2015-02-01

    The erbium-doped yttrium aluminum garnet (Er:YAG) laser is currently used for periodontal soft tissue management with favorable outcomes. However, the process of wound healing after Er:YAG laser (ErL) treatment has not been fully elucidated yet. The aim of this study was to investigate the gingival tissue healing after ErL ablation in comparison with that after electrosurgery (ElS). Gingival defects were created in 28 rats by ablation with ErL irradiation or ElS. The chronological changes in wound healing were evaluated using histological, histometrical, and immunohistochemical analyses. The ErL-ablated gingival tissue revealed much less thermal damage, compared to the ElS. In the ElS sites, the postoperative tissue destruction continued due to thermal damage, while in the ErL sites, tissue degradation was limited and the defects were re-epithelialized early. Heat shock protein (Hsp) 72/73 expression was detected abundantly remote from the wound in the ElS, whereas it was slightly observed in close proximity to the wound in the ErL sites. Hsp47 expression was observed in the entire connective tissue early in the wound healing and was found limited in the wound area later. This phenomenon proceeded faster in the ErL sites than in the ElS sites. Expression of proliferating cell nuclear antigen (PCNA) persisted in the epithelial tissue for a longer period in the ElS than that in the ErL. The ErL results in faster and more favorable gingival wound healing compared to the ElS, suggesting that the ErL is a safe and suitable tool for periodontal soft tissue management. PMID:24241972

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. The meteorological measurement system on the NASA ER-2 aircraft

    NASA Technical Reports Server (NTRS)

    Scott, Stan G.; Bui, T. Paul; Chan, K. Roland; Bowen, Stuart W.

    1988-01-01

    A Meteorological Measurement System (MMS) was designed for the high-altitude ER-2 aircraft (NASA 706). Through dedicated instrumentation installed on the aircraft and repeated calibrations, the MMS provides accurate in situ measurements of free-stream pressure, temperature, and the wind vector. The MMS has participated in two major high-altitude scientific expeditions, the Stratosphere-Troposphere Exchange Project (STEP) based in northern Australia and the Airborne Antarctic Ozone Experiment (AAOE) based in southern Chile. Key MMS subsystems are described. The MMS consists of a dedicated inertial navigation system (INS), a randome differential pressure system, a data acquisition system, and air data instrumentation. The MMS incorporates a high-resolution INS (Litton LIN-72RH model), which is specially configured and is updated at 25 Hz. The differential pressure system, consisting of two sets of pressure ports and transducers, is installed in the ER-2 radome to provide sensitive measurements of the airflow angles (angle of attack and angle of sideslip). The data acquisition system was designed to meet aircraft requirements of compactness and light weight (2 cu ft 50 lb) and for MMS requirements to sample, control, process, and store 45 parameters (some redundant) at a sampling rate up to 10 Hz. The MMS data are stored both in a tape recorder (20 MB) and a hermatically-sealed winchester hard disc (10 MB). Special and redundant instrumentation for temperature and pressure measurements were also installed on the aircraft.

  3. Sar1 assembly regulates membrane constriction and ER export

    PubMed Central

    Long, Kimberly R.; Yamamoto, Yasunori; Baker, Adam L.; Watkins, Simon C.; Coyne, Carolyn B.; Conway, James F.

    2010-01-01

    The guanosine triphosphatase Sar1 controls the assembly and fission of COPII vesicles. Sar1 utilizes an amphipathic N-terminal helix as a wedge that inserts into outer membrane leaflets to induce vesicle neck constriction and control fission. We hypothesize that Sar1 organizes on membranes to control constriction as observed with fission proteins like dynamin. Sar1 activation led to membrane-dependent oligomerization that transformed giant unilamellar vesicles into small vesicles connected through highly constricted necks. In contrast, membrane tension provided through membrane attachment led to organization of Sar1 in ordered scaffolds that formed rigid, uniformly nonconstricted lipid tubules to suggest that Sar1 organization regulates membrane constriction. Sar1 organization required conserved residues located on a unique C-terminal loop. Mutations in this loop did not affect Sar1 activation or COPII recruitment and enhanced membrane constriction, yet inhibited Sar1 organization and procollagen transport from the endoplasmic reticulum (ER). Sar1 activity was directed to liquid-disordered lipid phases. Thus, lipid-directed and tether-assisted Sar1 organization controls membrane constriction to regulate ER export. PMID:20624903

  4. 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.

  5. 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 μ m wavelength, 300 mJ maximum pulse energy, 140 μ 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 μ 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.

  6. Properties of the rotational bands in {sup 161}Er

    SciTech Connect

    Chen, L.; Zhou, X. H.; Wang, S. T.; Zhang, N. T.; Zhou, H. B.; Li, G. S.; Wang, H. X.; Ding, B.; Zhang, Y. H.; Zheng, Y.; Liu, M. L.; Ma, F.; Fang, Y. D.; Hua, W.; Guo, S.; Qiang, Y. H.; Lei, X. G.; Guo, Y. X.; Zhu, L. H.; Wu, X. G.

    2011-03-15

    High-spin states in {sup 161}Er have been studied experimentally using the {sup 150}Nd({sup 16}O,5n) reaction at a beam energy of 86 MeV. The 5/2{sup +}[642], 3/2{sup -}[521], and 11/2{sup -}[505] bands are extended up to high-spin states, and particularly the {alpha}=-1/2 branch of the ground state 3/2{sup -}[521] band is revised significantly. The relatively enhanced E1 transitions from the 3/2{sup -}[521] band to the 5/2{sup +}[642] band are observed. The band properties are analyzed within the framework of a triaxial particle-rotor model, and near-prolate shape and triaxial deformation are proposed to the 3/2{sup -}[521] and 5/2{sup +}[642] bands, respectively. Signature inversion occurs in the 3/2{sup -}[521] band after the band crossing in {sup 161}Er, and the systematics of the signature inversion associated with the 3/2{sup -}[521] configuration are discussed. By analyzing the properties of the relatively enhanced E1 transitions, it is found that the R(E1/E2) values show angular momentum dependence before the band crossing, and these enhanced E1 transitions could be attributed to octupole softness.

  7. 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.

  8. 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.

  9. ER-2 High Altitude Solar Cell Calibration Flights

    NASA Technical Reports Server (NTRS)

    Myers, Matthew; Wolford, David; Snyder, David; Piszczor, Michael

    2015-01-01

    Evaluation of space photovoltaics using ground-based simulators requires primary standard cells which have been characterized in a space or near-space environment. Due to the high cost inherent in testing cells in space, most primary standards are tested on high altitude fixed wing aircraft or balloons. The ER-2 test platform is the latest system developed by the Glenn Research Center (GRC) for near-space photovoltaic characterization. This system offers several improvements over GRC's current Learjet platform including higher altitude, larger testing area, onboard spectrometers, and longer flight season. The ER-2 system was developed by GRC in cooperation with NASA's Armstrong Flight Research Center (AFRC) as well as partners at the Naval Research Laboratory and Air Force Research Laboratory. The system was designed and built between June and September of 2014, with the integration and first flights taking place at AFRC's Palmdale facility in October of 2014. Three flights were made testing cells from GRC as well as commercial industry partners. Cell performance data was successfully collected on all three flights as well as solar spectra. The data was processed using a Langley extrapolation method, and performance results showed a less than half a percent variation between flights, and less than a percent variation from GRC's current Learjet test platform.

  10. Biocompatibility of Er:YSGG laser radiated root surfaces

    NASA Astrophysics Data System (ADS)

    Benthin, Hartmut; Ertl, Thomas P.; Schmidt, Dirk; Purucker, Peter; Bernimoulin, J.-P.; Mueller, Gerhard J.

    1996-01-01

    Pulsed Er:YAG and Er:YSGG lasers are well known to be effective instruments for the ablation of dental hard tissues. Developments in the last years made it possible to transmit the laser radiation at these wavelengths with flexible fibers. Therefore the application in the periodontal pocket may be possible. The aim of this study was to evaluate the in-vitro conditions to generate a bioacceptable root surface. Twenty extracted human teeth, stored in an antibiotic solution, were conventionally scaled, root planed and axially separated into two halves. Two main groups were determined. With the first group laser radiation was carried out without and in the second group with spray cooling. The laser beam was scanned about root surface areas. Laser parameters were varied in a selected range. The biocompatibility was measured with the attachment of human gingival fibroblasts and directly compared to conventionally treated areas of the root surfaces. The fibroblasts were qualified and counted in SEM investigations. On conventionally treated areas gingival fibroblasts show the typical uniform cover. In dependance on the root roughness after laser treatment the fibroblasts loose the typical parallel alignment to the root surface. With spray cooling a better in-vitro attachment could be obtained. Without spray cooling the higher increase in temperature conducted to less bioacceptance by the human gingival fibroblasts to the root surface. These results show the possibility of producing bioacceptable root surfaces with pulsed laser radiation in the range of very high water absorption near 3 micrometer.

  11. Hollow waveguide for giant Er:YAG laser pulses transfer

    NASA Astrophysics Data System (ADS)

    Nemec, Michal; Jelinkova, Helena; Koranda, Petr; Cech, Miroslav; Sulc, Jan; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

    2004-06-01

    Short Er:YAG laser pulses were delivered by a cyclic olefin polymer coated silver hollow glass (COP/Ag) waveguide specially designed for a high power radiation. Er:YAG laser was Q-switched by an electro-optic shutter - LiNbO3 Pockels cell with Brewster angle cut input/output faces. The maximum energy output obtained from this system was 29 mJ with the length of pulse 69 ns corresponding to 420 kW output peak power. The system was working with the repetition rate of 1.5 Hz. A delivery system composed of a lens (f = 40 mm), protector and waveguide with the 700/850 μm diameter and 50 cm or 1 m length. The measured maximum delivered intensity was 86 MW/cm2 what corresponds to the transmission of 78.6 % for whole delivery system. Using of a sealed cap, this delivery system gives a possibility of the contact surgical treatment in many medicine branches, for example ophthalmology, urology or dentistry.

  12. 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.

  13. 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.

  14. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways

    PubMed Central

    Timmins, Jenelle M.; Ozcan, Lale; Seimon, Tracie A.; Li, Gang; Malagelada, Cristina; Backs, Johannes; Backs, Thea; Bassel-Duby, Rhonda; Olson, Eric N.; Anderson, Mark E.; Tabas, Ira

    2009-01-01

    ER stress–induced apoptosis is implicated in various pathological conditions, but the mechanisms linking ER stress–mediated signaling to downstream apoptotic pathways remain unclear. Using human and mouse cell culture and in vivo mouse models of ER stress–induced apoptosis, we have shown that cytosolic calcium resulting from ER stress induces expression of the Fas death receptor through a pathway involving calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ) and JNK. Remarkably, CaMKIIγ was also responsible for processes involved in mitochondrial-dependent apoptosis, including release of mitochondrial cytochrome c and loss of mitochondrial membrane potential. CaMKII-dependent apoptosis was also observed in a number of cultured human and mouse cells relevant to ER stress–induced pathology, including cultured macrophages, endothelial cells, and neuronal cells subjected to proapoptotic ER stress. Moreover, WT mice subjected to systemic ER stress showed evidence of macrophage mitochondrial dysfunction and apoptosis, renal epithelial cell apoptosis, and renal dysfunction, and these effects were markedly reduced in CaMKIIγ-deficient mice. These data support an integrated model in which CaMKII serves as a unifying link between ER stress and the Fas and mitochondrial apoptotic pathways. Our study also revealed what we believe to be a novel proapoptotic function for CaMKII, namely, promotion of mitochondrial calcium uptake. These findings raise the possibility that CaMKII inhibitors could be useful in preventing apoptosis in pathological settings involving ER stress–induced apoptosis. PMID:19741297

  15. CDIP1-BAP31 complex transduces apoptotic signals from endoplasmic reticulum to mitochondria under ER stress

    PubMed Central

    Chu, Kiki; Hwang, So-Young; Yoon, Kyoung Wan; Byun, Sanguine; Hiraki, Masatsugu; Mandinova, Anna; Lee, Sam W.

    2013-01-01

    SUMMARY Resolved ER stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a pro-apoptotic p53 target, CDIP1, acts as a key signal transducer of ER stress-mediated apoptosis. We identify BAP31, B-cell receptor-associated protein 31, as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent tBid and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER stress-mediated apoptosis. Together, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a novel mechanism for establishing an ER-mitochondrial cross-talk for ER stress-mediated apoptosis signaling. PMID:24139803

  16. Chaperone gp96 mediates ER-α36 cell membrane expression.

    PubMed

    Hou, Junwei; Deng, Mengmeng; Li, Xin; Liu, Weiwei; Chu, Xiaoyu; Wang, Jing; Chen, Feng; Meng, Songdong

    2015-10-13

    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

  17. Polar-Molecule Electrorheological Pm-Er Fluids:. the Properties and Evaluations

    NASA Astrophysics Data System (ADS)

    Lu, Kunquan; Shen, Rong; Wang, Xuezhao; Wang, De; Sun, Gang

    In recent years, a new type ER fluids named as polar-molecule-dominated electrorheological (PM-ER) fluids have been developed, of which the yield stress can reach more than 100 kPa and behaves a linear dependence on the electric field. A brief description on the composition and synthesizing method for the materials is given. The main merits of PM-ER fluid are as follows: high yield stress, the shear stress increasing with shear rate up to more than 103 s-1, low current density, rapid electric response and anti-sedimentation. Some perspectives on PM-ER fluid and its applications are presented.

  18. 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.

  19. When under pressure, get closer: PERKing up membrane contact sites during ER stress.

    PubMed

    van Vliet, Alexander R; Agostinis, Patrizia

    2016-04-15

    The endoplasmic reticulum (ER) is the main hub of cellular Ca(2+)signalling and protein synthesis and folding. The ER moreover is the central player in the formation of contact sites with other organelles and structures, including mitochondria, plasma membrane (PM) and endosomes. The most studied of these, the ER-mitochondria contact sites, are crucial regulators of cellular Ca(2+)homoeostasis, metabolism and cell death signalling. Protein kinase RNA-like ER kinase (PERK), an ER stress kinase and crucial signalling protein in the unfolded protein response (UPR), was found to be able to orchestrate contact sites between the ER and mitochondria and to be indispensable for the pre-apoptotic trafficking of calreticulin (CRT) at the PM during immunogenic cell death (ICD). Furthermore, PERK has recently been linked with ER and PM contact sites through the mechanism of store-operated Ca(2+)entry (SOCE). Here we discuss emerging findings disclosing novel roles of the ER stress sensor PERK in orchestrating inter-organellar communication in the context of ER stress. PMID:27068961

  20. 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

  1. 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

  2. Role of ER-α36 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-α36). The relationship between cancerous cells and ER-α36 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-α36, 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-α36 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-α36 is a key factor in increasing risk of breast cancer. However, in several recent studies, the action mechanisms of ER-α36 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-α36, then discuss these related estrogenic effects of ER-α36, and lastly give the predictive and prognostic value of ER-α36 as diagnostic marker by mediating typical XEs in breast cancer. PMID:26337277

  3. 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

  4. 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

  5. Sorting nexin 17 regulates ApoER2 recycling and reelin signaling.

    PubMed

    Sotelo, Pablo; Farfán, Pamela; Benitez, María Luisa; Bu, Guojun; Marzolo, María-Paz

    2014-01-01

    ApoER2 is a member of the low density-lipoprotein receptor (LDL-R) family. As a receptor for reelin, ApoER2 participates in neuronal migration during development as well as synaptic plasticity and survival in the adult brain. A previous yeast two-hybrid screen showed that ApoER2 is a binding partner of sorting nexin 17 (SNX17) - a cytosolic adaptor protein that regulates the trafficking of several membrane proteins in the endosomal pathway, including LRP1, P-selectin and integrins. However, no further studies have been performed to investigate the role of SNX17 in ApoER2 trafficking and function. In this study, we present evidence based on GST pull-down and inmunoprecipitation assays that the cytoplasmic NPxY endocytosis motif of ApoER2 interacts with the FERM domain of SNX17. SNX17 stimulates ApoER2 recycling in different cell lines including neurons without affecting its endocytic rate and also facilitates the transport of ApoER2 from the early endosomes to the recycling endosomes. The reduction of SNX17 was associated with accumulation of an ApoER2 carboxy-terminal fragment (CTF). In addition, in SNX17 knockdown cells, constitutive ApoER2 degradation was not modified, whereas reelin-induced ApoER2 degradation was increased, implying that SNX17 is a regulator of the receptor's half-life. Finally, in SNX17 silenced hippocampal and cortical neurons, we underscored a positive role of this endosomal protein in the development of the dendritic tree and reelin signaling. Overall, these results establish the role of SNX17 in ApoER2 trafficking and function and aid in identifying new links between endocytic trafficking and receptor signaling. PMID:24705369

  6. Influence of undoped YAG cap on diode-pumped composite YAG/Er:Yb:glass laser

    NASA Astrophysics Data System (ADS)

    Šulc, Jan; Jelínková, Helena; Nejezchleb, Karel; Škoda, Václav

    2012-03-01

    Two samples of Er-Yb doped phosphate glass were tested as a gain medium of longitudinally diode pumped laser. One sample was a simple Er:Yb:glass rod (length 2.8 mm), second sample was composite rod consisting of 2.8mm long Er:Yb:glass and 6mm long YAG crystal. Diameter of both samples was 6 mm. Dopant concentration for Er:Yb:glass was 0.75 × 1020 cm-3 Er and 1.7 × 1021 cm-3 Yb. The goal of the experiment was to investigate an effect of the undoped YAG cap on the Er:Yb:glass laser operation. The active medium, fixed in cupreous heatsink, was placed inside the 150mm long resonator consisted of a flat pumping mirror (HR @ 1.52-1.65 μm, HT @ 0.97 μm) and curved output coupler (r = 150 mm, R = 97% @ 1.52-1.61 μm). For Er:Yb:glass pumping a fiber coupled laser diode, operating in pulsed regime, was used. The pumping pulse width, energy, and wavelength were 1 ms, 10 mJ, and 975 nm, respectively. The decrease of Er:Yb:glass laser output pulse energy with increasing pumping repetition rate was observed for both samples. In case of simple Er:Yb:glass the energy dropped from 1.4mJ to 0.6mJ after pumping duty cycle increase from 0.5% to 6 %. In case of composite YAG/Er:Yb:glass active medium the relative output energy decrease was only 20% for pumping duty cycle increase from 0.5% to 10%. This result showed that the slope of the output energy decrease with increasing duty cycle was approximately four times slower for composite active media in comparison with simple Er:Yb:glass.

  7. 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.

  8. A Surfactant Bridge Model for the Nonlinear Electrorheological Effects of Surfactant-Activated ER Suspensions.

    PubMed

    Kim, Young Dae

    2001-04-15

    In surfactant-activated electrorheological (ER) suspensions it is observed that the ER response shows linear ER behavior (F~E(2)) at small surfactant concentrations and nonlinear ER behavior (F~E(n), n approximately 1) at large surfactant concentrations. Here, a surfactant bridge model is developed to explain the nonlinear ER behavior of surfactant-activated ER suspensions. The model shows that the formation and size of a surfactant bridge depend on various variables, especially the electric field strength, the surfactant surface tension, and the initially adsorbed amount of surfactants on particles. The predicted dependence of the formation and size of a surfactant bridge on the electric field strength and the initially adsorbed amount of surfactants is consistent with the observations. Also, the model indicates that there is a critical minimum electric field E(crit) for the formation of a surfactant bridge, and the estimated E(crit) shows good agreement with the observations. The force acting between particles is composed of the electrostatic force and force associated with surface tension. However, it is found that the contribution of the force associated with surface tension can be ignored and the electrostatic force is dominant regardless of the formation of surfactant bridges between particles. When surfactant bridges are formed between particles, the predicted force shows nonlinear ER behavior (F~E(n), n approximately 1), consistent with the observed nonlinear ER behavior at large surfactant concentrations. When no surfactant bridge is formed, the predicted force is proportional to the electric field squared (F~E(2)), consistent with the interfacial polarization. The model can successfully predict the nonlinear ER behavior at large surfactant concentrations, confirming that the nonlinear ER behavior of surfactant-activated ER suspensions arises from the observed formation of surfactant bridges between particles. Copyright 2001 Academic Press. PMID:11401368

  9. 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.

  10. 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

  11. Radiative and non radiative spectroscopic properties of Er 3+ ion in tellurite glass

    NASA Astrophysics Data System (ADS)

    Kumar, G. A.; De la Rosa, E.; Desirena, H.

    2006-04-01

    We have investigated in detail the mechanism of infrared emission and upconversion emission of Er3+ in tellurite glass as a function of the dopant concentration. Both the infrared and upconversion emissions are competing processes and the efficiency of infrared emission at 1534 nm is 100% at the lowest Er content (0.5 mol%) and reduces to 50% at higher dopant concentration (>2 mol%). The green upconversion emission at 548 nm is mainly due to the excited state absorption (ESA) from 4I11/2, which populate the 4F7/2 level. In addition to this, the possible energy transfer (ET) through Er3+(4I11/2) + Er3+(4I11/2) → Er3+(4F7/2) + Er3+(4I15/2) can also results in the green emission as is noticed from the concentration dependent efficiency change of the green emission. The fluorescence quenching of green emission with Er concentration may be related with the cross relaxation (CR) process 2H11/2 + 4I15/2 → 4I9/2 + 4I13/2. The red emission is due to the combined effect of the ESA from level 4I13/2 to 4F9/2, the energy transfer process described by Er3+(4I13/2) + Er3+(4I11/2) → Er3+(4F9/2) + Er3+(4I15/2) and the cross relaxation process.

  12. 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.

  13. 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

    Reilly, B A; Kraynack, B A; VanRheenen, S M; Waters, M G

    2001-12-01

    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 approximately 80 and approximately 55 kDa. The approximately 80-kDa protein has been identified as Tip20p, a protein that others have shown to exist in a tight complex with Sec20p, which is approximately 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 delta-subunit of the retrograde COPI coat, Ret2p, and discuss possible roles for this interaction. PMID:11739780

  14. 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.

  15. Crystal and molecular structure of the coordination compounds of Er3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [Er L {2/1}(NO3)2]2[Er(NO3)2(H2O)5]0.333(NO3)2.333 · 2.833H2O and its ethyl substituted derivative [Er L {2/2}(NO3)2][Er(NO3)5]0.5 · 0.5H2O

    NASA Astrophysics Data System (ADS)

    Polyakova, I. N.; Baulin, V. E.; Ivanova, I. S.; Pyatova, E. N.; Sergienko, V. S.; Tsivadze, A. Yu.

    2015-01-01

    The coordination compounds of Er3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [Er L {2/1}(NO3)2]2[Er(NO3)2(H2O)5]0.333(NO3)2.333 · 2.833H2O ( I) and its ethyl substituted derivative [Er L {2/2}(NO3)2][Er(NO3)5]0.5 · 0.5H2O ( II) are synthesized and their crystal structures are studied. I and II contain [Er L 2(NO3)2]+ complex cations of identical composition and close structure. The eight-vertex polyhedron of the Er atom in the shape of a distorted octahedron with two split trans vertices is formed by the O atoms of the phosphoryl groups of L ligands and nitrate anions. L ligands close nine-membered metallocycles. The structures contain spacious channels which are populated differently, namely, by disordered [Er(NO3)2(H2O)5]+ complex cations, NO{3/-} anions, and crystallization water molecules in I and disordered [Er(NO3)5]2- complex anions and crystallization water molecules in II. The IR spectra of I and II are studied.

  16. 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.

  17. 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.

  18. The Meteorological Measurement System on the NASA ER-2 aircraft

    NASA Technical Reports Server (NTRS)

    Scott, Stan G.; Bui, T. Paul; Chan, K. Roland; Bowen, Stuart W.

    1990-01-01

    A Meteorological Measurement System (MMS) was designed and installed on one of the NASA high-altitude ER-2 aircraft (NASA 706). The MMS provides in situ measurements of free-stream pressure (+ or - 0.3 mb), temperature (+ or - 0.3 C), and wind vector (+ or - 1 m/s). It incorporates a high-resolution inertial navigation system specially configured for scientific applications, a radome differential pressure system for measurements of the airflow angles, and a compact, computer-controlled data acquisition system to sample, process and store 45 variables on tape and on disk. The MMS hardware and software development is described, and resolution and accuracy of the instrumentation discussed. Custom software facilitates preflight system checkout, inflight data acquisition, and fast postflight data download. It accommodates various modes of MMS data: analog and digital, serial and parallel, and synchronous and asynchronous. Flight results are presented to demonstrate the capability of the system.

  19. Optical cooling in Er3+:KPb2Cl5.

    PubMed

    Condon, Nicholas J; Bowman, Steven R; O'Connor, Shawn P; Quimby, Richard S; Mungan, Carl E

    2009-03-30

    For the first time, optical cooling has been observed in the (4)I(13/2) excited state of erbium(III), using the low phonon energy host materal, potassium lead chloride (KPb(2)Cl(2)). Cooling was observed when samples were pumped at wavelengths longer than 1557 nm, 17 nm longer than the mean fluorescence wavelength of 1540 nm, which implies a nonradiative heat load of 1.1% for the (4)I(13/2)-->(4)I(15/2) transition. When pumped at 1568 nm, the total cooling efficiency was 0.38% of the absorbed power. These results highlight the potential of Er(3+):KPb(2)Cl(5) as a material for lasers operating in an eye safe spectral region. PMID:19333313

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Polypeptide from Chlamys farreri restores endoplasmic reticulum (ER) redox homeostasis, suppresses ER stress, and inhibits ER stress-induced apoptosis in ultraviolet B-irradiated HaCaT cells

    PubMed Central

    Xie, Jing; Zhong, Feng; Han, Yantao; Gao, Hui; Wang, Chunbo; Peng, Jianjun

    2015-01-01

    Objective: To investigate the effects of polypeptide from Chlamys farreri (PCF) on ultraviolet B (UVB)-induced apoptosis in human keratinocyte HaCaT cells. Methods: In HaCaT cells at 4 h or 18 h after UVB irradiation, the cell viability was measured by MTT assay. Cellular apoptosis was detected with annexin V-FITC/PI staining by flow cytometry. The expression levels of PDI, Ero-1α, GRP78, and CHOP were assessed by Western blot analysis. Mitochondrial membrane potential (MMP) was measured by fluorescent probe JC-1. Caspase activities were detected with fluorogenic substrates. Results: PCF alleviated cell viability loss and inhibited apoptosis in HaCaT cells after UVB irradiation. Moreover, PCF increased the expression levels of PDI and Ero-1α, which were related with the ER redox homeostasis. Furthermore, PCF treatment inhibited the expression of GRP78 at 4 h after UVB irradiation, and suppressed CHOP expression at 18 h post-irradiation, indicating that PCF could inhibit UVB-evoked ER stress in the early stage post-irradiation, and suppress the ER stress-induced apoptosis in the late stage. In addition, PCF alleviated UVB-induced MMP loss, and inhibited the activation of caspase-9/-3, in HaCaT cells after UVB irradiation. On the other hand, MMP loss and caspase-9/-3 activation could be partly blocked by the ER stress inhibitor 4-PBA. Conclusions: PCF inhibits UVB-induced apoptosis through restoring ER redox homeostasis, suppressing ER stress, and inhibiting ER stress-induced mitochondrial apoptosis in HaCaT cells. These findings provide evidence for the mechanism underlying UVB-induced skin damages, and support the promising role of PCF in treatment of the diseases. PMID:26175857

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 7 CFR 1794.22 - Categorically excluded proposals requiring an ER.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Classification of Proposals § 1794.22 Categorically excluded proposals requiring an ER. (a) Electric and.... Proposed actions within this classification are: (1) Construction of electric power lines and associated... associated facilities and related electric power lines shall be covered in the ER; (9) Installation of...

  11. 7 CFR 1794.22 - Categorically excluded proposals requiring an ER.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Classification of Proposals § 1794.22 Categorically excluded proposals requiring an ER. (a) Electric and.... Proposed actions within this classification are: (1) Construction of electric power lines and associated... associated facilities and related electric power lines shall be covered in the ER; (9) Installation of...

  12. 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

  13. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

  14. Downregulation of E2F1 during ER stress is required to induce apoptosis.

    PubMed

    Pagliarini, Vittoria; Giglio, Paola; Bernardoni, Paolo; De Zio, Daniela; Fimia, Gian Maria; Piacentini, Mauro; Corazzari, Marco

    2015-03-15

    The endoplasmic reticulum (ER) has recently emerged as an alternative target to induce cell death in tumours, because prolonged ER stress results in the induction of apoptosis even in chemoresistant transformed cells. Here, we show that the DNA-damage-responsive pro-apoptotic factor E2F1 is unexpectedly downregulated during the ER stress-mediated apoptotic programme. E2F1 decline is a late event during the ER response and is mediated by the two unfolded protein response (UPR) sensors ATF6 and IRE1 (also known as ERN1). Whereas ATF6 directly interacts with the E2F1 promoter, IRE1 requires the involvement of the known E2F1 modulator E2F7, through the activation of its main target Xbp-1. Importantly, inhibition of the E2F1 decrease prevents ER-stress-induced apoptosis, whereas E2F1 knockdown efficiently sensitises cells to ER stress-dependent apoptosis, leading to the upregulation of two main factors in the UPR pro-apoptotic execution phase, Puma and Noxa (also known as BBC3 and PMAIP1, respectively). Our results point to a novel key role of E2F1 in the cell survival/death decision under ER stress, and unveil E2F1 inactivation as a valuable novel potential therapeutic strategy to increase the response of tumour cells to ER stress-based anticancer treatments. PMID:25616897

  15. 7 CFR 1794.22 - Categorically excluded proposals requiring an ER.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... environmental audit can be substituted for the ER. (12) Installing a heat recovery steam generator and steam... covered in the ER. (b) Water and waste program. For certain proposed actions, applications for financial... waste projects. An EA must be prepared if a proposed action normally classified as a CE meets any of...

  16. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in plants.

    PubMed

    Wan, Shucen; Jiang, Liwen

    2016-05-01

    Being a major factory for protein synthesis, assembly, and export, the endoplasmic reticulum (ER) has a precise and robust ER quality control (ERQC) system monitoring its product line. However, when organisms are subjected to environmental stress, whether biotic or abiotic, the levels of misfolded proteins may overwhelm the ERQC system, tilting the balance between the capacity of and demand for ER quality control and resulting in a scenario termed ER stress. Intense or prolonged ER stress may cause damage to the ER as well as to other organelles, or even lead to cell death in extreme cases. To avoid such serious consequences, cells activate self-rescue programs to restore protein homeostasis in the ER, either through the enhancement of protein-folding and degradation competence or by alleviating the demands for such reactions. These are collectively called the unfolded protein response (UPR). Long investigated in mammalian cells and yeasts, the UPR is also of great interest to plant scientists. Among the three branches of UPR discovered in mammals, two have been studied in plants with plant homologs existing of the ER-membrane-associated activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1). This review discusses the molecular mechanisms of these two types of UPR in plants, as well as the consequences of insufficient UPR, with a focus on experiments using model plants. PMID:26060134

  17. 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...

  18. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance....72 (a), (b), (c), (d), (e) (concentration set at 0.1 percent), (f), (g)(1)(iv), (g)(1)(vi),...

  19. 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...

  20. 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...

  1. 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.

  2. Comment on “Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling”

    PubMed Central

    Reid, DW; Nicchitta, CV

    2016-01-01

    Jan et al. propose that ribosomes translating secretome mRNAs are recruited to the ER upon emergence of the signal peptide and return to the cytosol following termination. A thorough accounting of their controls demonstrates, however, that ribosomes are retained on the ER through many full cycles of translation. PMID:26068841

  3. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Water control management (ER 1110-2-240). 222.5 Section 222.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a) Purpose. This regulation prescribes...

  4. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Water control management (ER 1110-2-240). 222.5 Section 222.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a) Purpose. This regulation prescribes...

  5. 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

  6. 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...

  7. 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.

  8. All polarization-maintaining Er fiber-based optical frequency combs with nonlinear amplifying loop mirror.

    PubMed

    Kuse, N; Jiang, J; Lee, C-C; Schibli, T R; Fermann, M E

    2016-02-01

    A fully stabilized all polarization-maintaining Er frequency comb with a nonlinear amplifying loop mirror with below 0.2 rad carrier-envelope-offset frequency phase noise is demonstrated. The integrated timing jitter is measured as 40 attosecond from 10 kHz to 10 MHz, which is the lowest value of any Er fiber frequency comb to date. PMID:26906874

  9. Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides.

    PubMed

    Dickson, Eamonn J; Jensen, Jill B; Vivas, Oscar; Kruse, Martin; Traynor-Kaplan, Alexis E; Hille, Bertil

    2016-04-11

    Endoplasmic reticulum-plasma membrane (ER-PM) contact sites play an integral role in cellular processes such as excitation-contraction coupling and store-operated calcium entry (SOCE). Another ER-PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER-PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2 Activation of G protein-coupled receptors that deplete PM PI(4,5)P2disrupts E-Syt2-mediated ER-PM junctions, reducing Sac1's access to the PM and permitting PM PI(4)P and PI(4,5)P2to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER-PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes. PMID:27044890

  10. 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

  11. 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

  12. 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)...

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. 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

  18. 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

  19. 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.

  20. Analysis of upconversion luminescence in Yb3+/Er3+ co-doped tellurite optical fiber

    NASA Astrophysics Data System (ADS)

    Mazerski, Wojciech; Kochanowicz, Marcin; Dorosz, Dominik

    2013-10-01

    In the paper the analysis of upconversion luminescence in Yb3+/Er3+ co-doped tellurite glass and optical fiber has been investigated. Upconversion luminescence at 525 nm, 546 nm, 651 nm corresponding to the Er3+: 2H11/2→4I15/2, 4S3/2→4I15/2, (4F9/2→4I15/2) transitions, respectively was obtained as a result of energy transfer between Yb3+ and Er3+ ions. Developed tellurite glass characterized by highest intensity of upconversion luminescence (0.5mol% Yb2O3/0.1mol% Er2O3) was used as core of optical fiber. The analysis of influence of Yb3+/Er3+ co-doped tellurite optical fiber length on upconversion emission spectra was examinated.

  1. Self-assembled infrared-luminescent Er-Si-O crystallites on silicon

    SciTech Connect

    Isshiki, H.; Dood, M.J.A. de; Polman, A.; Kimura, T.

    2004-11-08

    Optically active and electrically excitable erbium complexes on silicon are made by wet-chemical synthesis. The single-crystalline Er-Si-O compound is formed by coating a Si(100) substrate with an ErCl{sub 3}/ethanol solution, followed by rapid thermal oxidation and annealing. Room-temperature Er-related 1.53 {mu}m photoluminescence is observed with a peak linewidth as small as 4 meV. The complexes can be excited directly into the Er intra-4f states, or indirectly, through photocarriers. Er concentrations as high as 14 at. % are achieved, incorporated in a crystalline lattice with a 0.9 nm periodicity. Thermal quenching at room temperature is only a factor 5, and the lifetime at 1.535 {mu}m is 200 {mu}s.

  2. The seipin complex Fld1/Ldb16 stabilizes ER-lipid droplet contact sites.

    PubMed

    Grippa, Alexandra; Buxó, Laura; Mora, Gabriel; Funaya, Charlotta; Idrissi, Fatima-Zahra; Mancuso, Francesco; Gomez, Raul; Muntanyà, Júlia; Sabidó, Eduard; Carvalho, Pedro

    2015-11-23

    Lipid droplets (LDs) are storage organelles consisting of a neutral lipid core surrounded by a phospholipid monolayer and a set of LD-specific proteins. Most LD components are synthesized in the endoplasmic reticulum (ER), an organelle that is often physically connected with LDs. How LD identity is established while maintaining biochemical and physical connections with the ER is not known. Here, we show that the yeast seipin Fld1, in complex with the ER membrane protein Ldb16, prevents equilibration of ER and LD surface components by stabilizing the contact sites between the two organelles. In the absence of the Fld1/Ldb16 complex, assembly of LDs results in phospholipid packing defects leading to aberrant distribution of lipid-binding proteins and abnormal LDs. We propose that the Fld1/Ldb16 complex facilitates the establishment of LD identity by acting as a diffusion barrier at the ER-LD contact sites. PMID:26572621

  3. 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.

  4. 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.

  5. Correlation between O/Er Content Ratio and Photoluminescence Intensity of (Er, O)-Doped Hydrogenated Amorphous Si Thin Films Prepared by a Catalytic Chemical Vapor Deposition/Laser Ablation Hybrid Process

    NASA Astrophysics Data System (ADS)

    Sakai, Joe; Masuda, Atsushi; Akiyama, Haruo; Eryu, Osamu; Nakashima, Kenshiro; Matsumura, Hideki

    2004-07-01

    (Er, O)-doped hydrogenated amorphous Si (a-Si:H) thin films were prepared on Si or SiO2 substrates by a novel catalytic chemical vapor deposition (Cat-CVD)/laser ablation hybrid process which simultaneously performs a Cat-CVD of a-Si:H matrices and a doping of laser-ablated (Er, O) from an Er2O3 sintered target. These (Er, O)-doped a-Si:H films showed excellent photoluminescence (PL) properties in spite of the low temperature of the process (200°C during deposition and no postannealing). The Er and O contents of these films were evaluated by Rutherford backscattering and non-Rutherford elastic resonance scattering (NRERS), respectively. It was clarified that the dependence of the (Er, O) content on ambient pressure was not identical for O and Er. Thus, the O/Er content ratio, correlated to the PL intensity, strongly depended on the ambient pressure.

  6. The Aggregation-Prone Intracellular Serpin SRP-2 Fails to Transit the ER in Caenorhabditis elegans

    PubMed Central

    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.

    2015-01-01

    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

  7. 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

  8. 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.

  9. Guanabenz Interferes with ER Stress and Exerts Protective Effects in Cardiac Myocytes

    PubMed Central

    Neuber, Christiane; Uebeler, June; Schulze, Thomas; Sotoud, Hannieh; El-Armouche, Ali; Eschenhagen, Thomas

    2014-01-01

    Endoplasmic reticulum (ER) stress has been implicated in a variety of cardiovascular diseases. During ER stress, disruption of the complex of protein phosphatase 1 regulatory subunit 15A and catalytic subunit of protein phosphatase 1 by the small molecule guanabenz (antihypertensive, α2-adrenoceptor agonist) and subsequent inhibition of stress-induced dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) results in prolonged eIF2α phosphorylation, inhibition of protein synthesis and protection from ER stress. In this study we assessed whether guanabenz protects against ER stress in cardiac myocytes and affects the function of 3 dimensional engineered heart tissue (EHT). We utilized neonatal rat cardiac myocytes for the assessment of cell viability and activation of ER stress-signalling pathways and EHT for functional analysis. (i) Tunicamycin induced ER stress as measured by increased mRNA and protein levels of glucose-regulated protein 78 kDa, P-eIF2α, activating transcription factor 4, C/EBP homologous protein, and cell death. (ii) Guanabenz had no measurable effect alone, but antagonized the effects of tunicamycin on ER stress markers. (iii) Tunicamycin and other known inducers of ER stress (hydrogen peroxide, doxorubicin, thapsigargin) induced cardiac myocyte death, and this was antagonized by guanabenz in a concentration- and time-dependent manner. (iv) ER stressors also induced acute or delayed contractile dysfunction in spontaneously beating EHTs and this was, with the notable exception of relaxation deficits under thapsigargin, not significantly affected by guanabenz. The data confirm that guanabenz interferes with ER stress-signalling and has protective effects on cell survival. Data show for the first time that this concept extends to cardiac myocytes. The modest protection in EHTs points to more complex mechanisms of force regulation in intact functional heart muscle. PMID:24892553

  10. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    SciTech Connect

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 ; Hung, Mien-Chie; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung 404, Taiwan; Asia University, Taichung 413, Taiwan

    2010-09-03

    Research highlights: {yields} ARF1 activation is involved in the EGFR transport to the ER and the nucleus. {yields} Assembly of {gamma}-COP coatomer mediates EGFR transport to the ER and the nucleus. {yields} Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH{sub 2}-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with {gamma}-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. New Actuators Using ER Fluid and Their Applications to Force Display Devices in Virtual Reality and Medical Treatments

    NASA Astrophysics Data System (ADS)

    Furusho, Junji; Sakaguchi, Masamichi

    We developed ER actuators with low inertia. ER actuator is a torque-controllable clutch which uses an electrorheological fluid. It is shown that this actuator has good properties for force display device, physical therapy treatment, etc. We developed new force display devices for virtual reality which use ER actuators.

  16. 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

  17. Pre-emptive Quality Control Protects the ER from Protein Overload via the Proximity of ERAD Components and SRP.

    PubMed

    Kadowaki, Hisae; Nagai, Atsushi; Maruyama, Takeshi; Takami, Yasunari; Satrimafitrah, Pasjan; Kato, Hironori; Honda, Arata; Hatta, Tomohisa; Natsume, Tohru; Sato, Takashi; Kai, Hirofumi; Ichijo, Hidenori; Nishitoh, Hideki

    2015-11-01

    Cells possess ER quality control systems to adapt to ER stress and maintain their function. ER-stress-induced pre-emptive quality control (ER pQC) selectively degrades ER proteins via translocational attenuation during ER stress. However, the molecular mechanism underlying this process remains unclear. Here, we find that most newly synthesized endogenous transthyretin proteins are rerouted to the cytosol without cleavage of the signal peptide, resulting in proteasomal degradation in hepatocytes during ER stress. Derlin family proteins (Derlins), which are ER-associated degradation components, reroute specific ER proteins, but not ER chaperones, from the translocon to the proteasome through interactions with the signal recognition particle (SRP). Moreover, the cytosolic chaperone Bag6 and the AAA-ATPase p97 contribute to the degradation of ER pQC substrates. These findings demonstrate that Derlins-mediated substrate-specific rerouting and Bag6- and p97-mediated effective degradation contribute to the maintenance of ER homeostasis without the need for translocation. PMID:26565908

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

    PubMed Central

    Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

    2014-01-01

    Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

  3. 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

  4. STIM1L traps and gates Orai1 channels without remodeling the cortical ER.

    PubMed

    Saüc, Sophie; Bulla, Monica; Nunes, Paula; Orci, Lelio; Marchetti, Anna; Antigny, Fabrice; Bernheim, Laurent; Cosson, Pierre; Frieden, Maud; Demaurex, Nicolas

    2015-04-15

    STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca(2+) entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca(2+) influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca(2+) imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1(-/-)/Stim2(-/-) fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca(2+) elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. PMID:25736291

  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. 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

  7. Methods for studying ER stress and UPR markers in human cells.

    PubMed

    Kennedy, Donna; Samali, Afshin; Jäger, Richard

    2015-01-01

    Many experimentally induced or disease-related cellular dysfunctions stress the endoplasmic reticulum, commonly resulting in an accumulation of unfolded proteins in the ER lumen which is sensed by three ER-resident transmembrane proteins, PERK, ATF6, and IRE1. Their activation by such ER stress affects the unfolded protein response, which consists of a shutoff of protein translation and at the same time the switching-on of specific transcription factors that control genes which function to reduce the burden of unfolded proteins to the ER. Here, we describe two sets of methods for monitoring the occurrence of ER stress and UPR signaling in human cells by analyzing markers of activation of all three ER stress sensor proteins. The first set of methods is based on the qualitative and quantitative analysis of UPR-induced transcripts by qPCR. The second set of methods consists of Western blot-based analysis of UPR-induced proteins or protein modifications. Their combined analysis allows assessment of activation of all three ER stress-activated signaling pathways that in combination are characteristic for the UPR. PMID:25804744

  8. Unfolded protein response-induced ERdj3 secretion links ER stress to extracellular proteostasis.

    PubMed

    Genereux, Joseph C; Qu, Song; Zhou, Minghai; Ryno, Lisa M; Wang, Shiyu; Shoulders, Matthew D; Kaufman, Randal J; Lasmézas, 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

  9. 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; Lasmézas, 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

  10. 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 α-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 μm 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.

  11. ERAD and protein import defects in a sec61 mutant lacking ER-lumenal loop 7

    PubMed Central

    2013-01-01

    Background The Sec61 channel mediates protein translocation across the endoplasmic reticulum (ER) membrane during secretory protein biogenesis, and likely also during export of misfolded proteins for ER-associated degradation (ERAD). The mechanisms of channel opening for the different modes of translocation are not understood so far, but the position of the large ER-lumenal loop 7 of Sec61p suggests a decisive role. Results We show here that the Y345H mutation in L7 which causes diabetes in the mouse displays no ER import defects in yeast, but a delay in misfolded protein export. A complete deletion of L7 in Sec61p resulted in viable, cold- and tunicamycin-hypersensitive yeast cells with strong defects in posttranslational protein import of soluble proteins into the ER, and in ERAD of soluble substrates. Membrane protein ERAD was only moderately slower in sec61∆L7 than in wildtype cells. Although Sec61∆L7 channels were unstable in detergent, co-translational protein integration into the ER membrane, proteasome binding to Sec61∆L7 channels, and formation of hetero-heptameric Sec complexes were not affected. Conclusions We conclude that L7 of Sec61p is required for initiation of posttranslational soluble protein import into and misfolded soluble protein export from the ER, suggesting a key role for L7 in transverse gating of the Sec61 channel. PMID:24314051

  12. 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

  13. The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control

    PubMed Central

    Moustaqim-Barrette, Amina; Lin, Yong Q.; Pradhan, Sreeparna; Neely, Gregory G.; Bellen, Hugo J.; Tsuda, Hiroshi

    2014-01-01

    A familial form of Amyotrophic lateral sclerosis (ALS8) is caused by a point mutation (P56S) in the vesicle-associated membrane protein associated protein B (VapB). Human VapB and Drosophila Vap-33-1 (Vap) are homologous type II transmembrane proteins that are localized to the ER. However, the precise consequences of the defects associated with the P56S mutation in the endoplasmic reticulum (ER) and its role in the pathology of ALS are not well understood. Here we show that Vap is required for ER protein quality control (ERQC). Loss of Vap in flies shows various ERQC associated defects, including protein accumulation, ER expansion, and ER stress. We also show that wild type Vap, but not the ALS8 mutant Vap, interacts with a lipid-binding protein, Oxysterol binding protein (Osbp), and that Vap is required for the proper localization of Osbp to the ER. Restoring the expression of Osbp in the ER suppresses the defects associated with loss of Vap and the ALS8 mutant Vap. Hence, we propose that the ALS8 mutation impairs the interaction of Vap with Osbp, resulting in hypomorphic defects that might contribute to the pathology of ALS8. PMID:24271015

  14. The effects of ER morphology on synaptic structure and function in Drosophila melanogaster.

    PubMed

    Summerville, James B; Faust, Joseph F; Fan, Ethan; Pendin, Diana; Daga, Andrea; Formella, Joseph; Stern, Michael; McNew, James A

    2016-04-15

    Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-typeDrosophilamotor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 orthologatlatlorRtnl1loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss ofatlcauses age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior. PMID:26906425

  15. NOD1 and NOD2 signalling links ER stress with inflammation.

    PubMed

    Keestra-Gounder, A Marijke; Byndloss, Mariana X; Seyffert, Núbia; Young, Briana M; Chávez-Arroyo, Alfredo; Tsai, April Y; Cevallos, Stephanie A; Winter, Maria G; Pham, Oanh H; Tiffany, Connor R; de Jong, Maarten F; Kerrinnes, Tobias; Ravindran, Resmi; Luciw, Paul A; McSorley, Stephen J; Bäumler, Andreas J; Tsolis, Renée M

    2016-04-21

    Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1α. Once activated, IRE1α recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-κB pathway. Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors or nucleotide-binding oligomerization domain (NOD)-like receptors, detect tissue damage or microbial infection. However, it is not clear which PRRs have a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NOD-like receptor family of PRRs, are important mediators of ER-stress-induced inflammation in mouse and human cells. The ER stress inducers thapsigargin and dithiothreitol trigger production of the pro-inflammatory cytokine IL-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system effector protein VceC into host cells, is TRAF2, NOD1/2 and RIP2-dependent and can be reduced by treatment with the ER stress inhibitor tauroursodeoxycholate or an IRE1α kinase inhibitor. The association of NOD1 and NOD2 with pro-inflammatory responses induced by the IRE1α/TRAF2 signalling pathway provides a novel link between innate immunity and ER-stress-induced inflammation. PMID:27007849

  16. 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

  17. Activation of AMP-activated protein kinase inhibits ER stress and renal fibrosis.

    PubMed

    Kim, Hyosang; Moon, Soo Young; Kim, Joon-Seok; Baek, Chung Hee; Kim, Miyeon; Min, Ji Yeon; Lee, Sang Koo

    2015-02-01

    It has been suggested that endoplasmic reticulum (ER) stress facilitates fibrotic remodeling. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed ER stress induced by chemical ER stress inducers [tunicamycin (TM) and thapsigargin (TG)] and also nonchemical inducers in tubular HK-2 cells. We further investigated the in vivo effects of AMPK on ER stress and renal fibrosis. Western blot analysis, immunofluorescence, small interfering (si)RNA experiments, and immunohistochemical staining were performed. Metformin (the best known clinical activator of AMPK) suppressed TM- or TG-induced ER stress, as shown by the inhibition of TM- or TG-induced upregulation of glucose-related protein (GRP)78 and phosphorylated eukaryotic initiation factor-2α through induction of heme oxygenase-1. Metformin inhibited TM- or TG-induced epithelial-mesenchymal transitions as well. Compound C (AMPK inhibitor) blocked the effect of metformin, and 5-aminoimidazole-4-carboxamide-1β riboside (another AMPK activator) exerted the same effects as metformin. Transfection with siRNA targeting AMPK blocked the effect of metformin. Consistent with the results of cell culture experiments, metformin reduced renal cortical GRP78 expression and increased heme oxygenase-1 expression in a mouse model of ER stress-induced acute kidney injury by TM. Activation of AMPK also suppressed ER stress by transforming growth factor-β, ANG II, aldosterone, and high glucose. Furthermore, metformin reduced GRP78 expression and renal fibrosis in a mouse model of unilateral ureteral obstruction. In conclusion, AMPK may serve as a promising therapeutic target through reducing ER stress and renal fibrosis. PMID:25428127

  18. Characterization of Schizosaccharomyces pombe ER α-Mannosidase: A Reevaluation of the Role of the Enzyme on ER-associated Degradation

    PubMed Central

    Movsichoff, Federico; Castro, Olga A.; Parodi, Armando J.

    2005-01-01

    It has been postulated that creation of Man8GlcNAc2 isomer B (M8B) by endoplasmic reticulum (ER) α-mannosidase I constitutes a signal for driving irreparably misfolded glycoproteins to proteasomal degradation. Contrary to a previous report, we were able to detect in vivo (but not in vitro) an extremely feeble ER α-mannosidase activity in Schizosaccharomyces pombe. The enzyme yielded M8B on degradation of Man9GlcNAc2 and was inhibited by kifunensin. Live S. pombe cells showed an extremely limited capacity to demannosylate Man9GlcNAc2 present in misfolded glycoproteins even after a long residence in the ER. In addition, no preferential degradation of M8B-bearing species was detected. Nevertheless, disruption of the α-mannosidase encoding gene almost totally prevented degradation of a misfolded glycoprotein. This and other conflicting reports may be best explained by assuming that the role of ER mannosidase on glycoprotein degradation is independent of its enzymatic activity. The enzyme, behaving as a lectin binding polymannose glycans of varied structures, would belong together with its enzymatically inactive homologue Htm1p/Mnl1p/EDEM, to a transport chain responsible for delivering irreparably misfolded glycoproteins to proteasomes. Kifunensin and 1-deoxymannojirimycin, being mannose homologues, would behave as inhibitors of the ER mannosidase or/and Htm1p/Mnl1p/EDEM putative lectin properties. PMID:16079177

  19. Influence of Er(3+) concentration on the photoluminescence characteristics and excitation mechanism of Gd2O3:Er(3+) phosphor synthesized via a solid-state reaction method.

    PubMed

    Tamrakar, R K; Bisen, D P; Bramhe, N

    2015-08-01

    An Er(3+) -doped phosphor of Gd2O3(Gd2O3:Er(3+)) was prepared using a conventional solid-state reaction method. The structure and particle size were determined from X-ray powder diffraction measurements. The average particle size of the phosphor was in between 20 and 50 nm. The particle size and structure of the phosphor were further confirmed by transmission electron microscopy (TEM) analysis. Luminescence spectra were recorded under excitation wavelengths of 275, 380, 515 and 980 nm. The visible upconversion and downconversion luminescence spectra of the Gd2O3:Er(3+) phosphor were investigated as a function of Er(3+) ion concentration. The upconverted emission at 980 nm excitation shows enhanced red emission with respect to green emission as the dopant concentration increased. Similar results were observed for downconversion emission under 275 and 380 nm excitation wavelengths. The mechanisms responsible for populating the (4)S3/2 and (4)F9/2 levels, for green and red emissions, respectively, are different for different excitations and for different concentrations of Er(3+). PMID:25377641

  20. Transport Anisotropy in ErNi2B2C Along c-AXIS

    NASA Astrophysics Data System (ADS)

    Lee, W. C.

    The resistivities along c-axis ρc(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 ρab(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 Néel temperature TN originated from Er+3 sublattice.

  1. Resonantly pumped Kerr-lens mode-locked Er:YVO4 laser

    NASA Astrophysics Data System (ADS)

    Fromzel, Viktor; Ter-Gabrielyan, Nikolay

    2015-05-01

    We report on a Kerr lens, self-mode-locked Er3+:YVO4 laser, based on the high third order nonlinearity of the gain medium. The Er3+:YVO4 is resonantly pumped by a CW Er-fiber laser into the absorption band around 1538 nm and operates at ~ 1604 nm with a 1.8 W average output power and ~ 40% slope efficiency relative to the absorbed pump. The laser yields a pulse train at a 240 MHz repetition rate. The pulsewidth is estimated to fall between 15 and 100 psec.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [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

  7. CAPER: a chromosome-assembled human proteome browsER.

    PubMed

    Guo, Feifei; Wang, Dan; Liu, Zhongyang; Lu, Liang; Zhang, Wei; Sun, Haiyan; Zhang, Hongxing; Ma, Jie; Wu, Songfeng; Li, Ning; Jiang, Ying; Zhu, Weimin; Qin, Jun; Xu, Ping; Li, Dong; He, Fuchu

    2013-01-01

    High-throughput mass spectrometry and antibody-based experiments have begun to produce a large amount of proteomic data sets. Chromosome-based visualization of these data sets and their annotations can help effectively integrate, organize, and analyze them. Therefore, we developed a web-based, user-friendly Chromosome-Assembled human Proteome browsER (CAPER). To display proteomic data sets and related annotations comprehensively, CAPER employs two distinct visualization strategies: track-view for the sequence/site information and the correspondence between proteome, transcriptome, genome, and chromosome and heatmap-view for the qualitative and quantitative functional annotations. CAPER supports data browsing at multiple scales through Google Map-like smooth navigation, zooming, and positioning with chromosomes as the reference coordinate. Both track-view and heatmap-view can mutually switch, providing a high-quality user interface. Taken together, CAPER will greatly facilitate the complete annotation and functional interpretation of the human genome by proteomic approaches, thereby making a significant contribution to the Chromosome-Centric Human Proteome Project and even the human physiology/pathology research. CAPER can be accessed at http://www.bprc.ac.cn/CAPE . PMID:23256906

  8. Comparison of the room temperature 1.53 μm Er photoluminescence from flash lamp and furnace annealed Er-doped Ge-rich SiO2 layers

    NASA Astrophysics Data System (ADS)

    Kanjilal, A.; Prucnal, S.; Rebohle, L.; Voelskow, M.; Helm, M.; Skorupa, W.

    2010-06-01

    The furnace and flash-lamp annealing (FLA) temperature dependent variation in the room temperature 1.53 μm Er photoluminescence (PL) from Er-doped Ge-rich SiO2 layers is investigated. The appearance of the 1.53 μm Er PL is discussed in the framework of the phonon-assisted fluorescent resonant energy transfer from Ge-related luminescence-centers (LCs) to the Er3+. Detailed analyses suggest that in case of FLA the decrease in the 1.53 μm Er PL intensity is governed by the temperature dependent recrystallization of Ge nanoclusters, while for furnace-annealing it is associated with the reduction in the LC-Er3+ coupling due to Ge out-diffusion and the formation of Er-rich clusters with increasing temperature.

  9. 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

  10. 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

  11. Reduction of the 1.55 µm 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.; Żelechower, M.; Czerska, E.; Świderska, M.; Sozańska, 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 μm 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).

  12. Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells

    PubMed Central

    Christodoulou, Andri; Santarella-Mellwig, Rachel; Santama, Niovi

    2016-01-01

    ABSTRACT The mechanism of endoplasmic reticulum (ER) morphogenesis is incompletely understood. ER tubules are shaped by the reticulons (RTNs) and DP1/Yop1p family members, but the mechanism of ER sheet formation is much less clear. Here, we characterize TMEM170A, a human transmembrane protein, which localizes in ER and nuclear envelope membranes. Silencing or overexpressing TMEM170A in HeLa K cells alters ER shape and morphology. Ultrastructural analysis reveals that downregulation of TMEM170A specifically induces tubular ER formation, whereas overexpression of TMEM170A induces ER sheet formation, indicating that TMEM170A is a newly discovered ER-sheet-promoting protein. Additionally, downregulation of TMEM170A alters nuclear shape and size, decreases the density of nuclear pore complexes (NPCs) in the nuclear envelope and causes either a reduction in inner nuclear membrane (INM) proteins or their relocalization to the ER. TMEM170A interacts with RTN4, a member of the reticulon family; simultaneous co-silencing of TMEM170A and RTN4 rescues ER, NPC and nuclear-envelope-related phenotypes, implying that the two proteins have antagonistic effects on ER membrane organization, and nuclear envelope and NPC formation. PMID:26906412

  13. Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells.

    PubMed

    Christodoulou, Andri; Santarella-Mellwig, Rachel; Santama, Niovi; Mattaj, Iain W

    2016-04-15

    The mechanism of endoplasmic reticulum (ER) morphogenesis is incompletely understood. ER tubules are shaped by the reticulons (RTNs) and DP1/Yop1p family members, but the mechanism of ER sheet formation is much less clear. Here, we characterize TMEM170A, a human transmembrane protein, which localizes in ER and nuclear envelope membranes. Silencing or overexpressing TMEM170A in HeLa K cells alters ER shape and morphology. Ultrastructural analysis reveals that downregulation of TMEM170A specifically induces tubular ER formation, whereas overexpression of TMEM170A induces ER sheet formation, indicating that TMEM170A is a newly discovered ER-sheet-promoting protein. Additionally, downregulation of TMEM170A alters nuclear shape and size, decreases the density of nuclear pore complexes (NPCs) in the nuclear envelope and causes either a reduction in inner nuclear membrane (INM) proteins or their relocalization to the ER. TMEM170A interacts with RTN4, a member of the reticulon family; simultaneous co-silencing of TMEM170A and RTN4 rescues ER, NPC and nuclear-envelope-related phenotypes, implying that the two proteins have antagonistic effects on ER membrane organization, and nuclear envelope and NPC formation. PMID:26906412

  14. 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

  15. [Upconversion of oxide Y2O3 doped with (Yb3+ , Er3+) ions with 978 nm excitation].

    PubMed

    Liu, Huang-Qing; Wang, Ling-Ling; Li, Hong-Jian

    2006-08-01

    Two nanomaterials Y2O3 : Er3+ and Y2O3 : (Yb3+, Er3+) were prepared by combustion on the basis of reagents Y2O3, Yb2O3 and Er2O3. The corresponding host Y2O3 : (Yb3+, Er3+) was obtained by increasing calcination temperature. Upconversion emission was obtained under 978 nm LD excitation. Comparing nanopowder oxide Y2O3 : Er3+ with nanometer materials Y2O3 : (Yb3+, Er3+) with respect to upconversion spectra, the upconversion emission of the former mainly was green upconversion and that of the latter mainly red light. However, the upconversion emission of nanopowder Y2O3 : (Yb3+, Er3+) was different from that of its corresponding host, with main red upconversion emission for the former but main green upconversion emission on the latter. PMID:17058930

  16. 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.

  17. Study of 162Er via the (p , t) and (p ,p') reactions

    NASA Astrophysics Data System (ADS)

    Kisliuk, D.; Garrett, P. E.; Finlay, A.; Bianco, L.; Bildstein, V.; Burbadge, C.; Chagnon-Lessard, S.; Diaz Varela, A.; Dunlop, M. R.; Dunlop, R.; Finlay, P.; Jamieson, D.; Jigmeddorj, B.; Maclean, A. D.; Michetti-Wilson, J.; Leach, K. G.; Radich, A. J.; Rand, E.; Svensson, C. E.; Wong, J.; Ball, G. C.; Triambak, S.; Faestermann, T.; Hertenberger, R.; Wirth, H.-F.

    2015-10-01

    The nature of excited states in well-deformed nuclei pose a challenge in nuclear structure. In light of this, the study of 162Er via the 164Er (p , t) and 162Er (p ,p') reactions has been initiated to shed light on the structure of these excited states. The experiments were performed at the Maier-Leibnitz Laboratory using a 22 MeV proton beam on highly-enriched targets of 162,164Er and the reaction was analyzed with the Q3D spectrograph. Strong population in the (p , t) reaction of the 02+ state, far greater than other 0+ states, has been observed. Transition matrix elements for population of low-lying states in the (p ,p') reaction have also been extracted. Initial results from these experiments will be presented.

  18. 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.

  19. 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 ...

  20. New phenylpropanoid-substituted flavan-3-ols from Pu-er ripe tea.

    PubMed

    Tao, Mu-Ke; Xu, Min; Zhu, Hong-Tao; Cheng, Rong-Rong; Wang, Dong; Yang, Chong-Ren; Zhang, Ying-Jun

    2014-08-01

    Pu-er ripe tea is a special microbial post-fermented tea made from Pu-er raw tea, a kind of green tea produced from the leaves of Camellia sinensis var. assamica. It is one of the most consumed teas in the past two decades in China, due to its special flavor, taste, and beneficial effects. This work aimed to obtain diverse catechin structures from Pu-er ripe tea, which led to the isolation of four new phenylpropanoid-substituted flavan-3-ols, puerins C-F (1-4), together with four known flavan-3-ols, (+)-catechin (5), (-)-epicatechin (6), (+/-)-gallocatechin (7), and (-)-epigallocatechin (8). Their structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR, mass and CD spectra. Compounds 1-4, which could be formed in the post-fermentative process of Pu-er tea, were isolated for the first time from tea and Theaceae plant. PMID:25233599

  1. 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.

  2. A REACTIVITY PATTERN OF DISCRIMINATION OF ER AGONISM AND ANTAGONISM BASED ON 3-D MOLECULAR ATTRIBUTES

    EPA Science Inventory

    Various models have been developed to predict the relative binding affinity (RBA) of chemicals to estrogen receptors (ER). These models are important for prioritizing chemicals for screening in biological assays assessing the potential for endocrine disruption. One shortcoming of...

  3. 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.

  4. 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.

  5. Structural and photoluminescence properties of Ce, Dy, Er-doped ZnO nanoparticles

    SciTech Connect

    Jayachandraiah, C.; Kumar, K. Siva; Krishnaiah, G.

    2015-06-24

    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.

  6. 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.

  7. Calibration Results for J-ERS-1 SAR Data Produced by the Alaska SAR Facility

    NASA Technical Reports Server (NTRS)

    Freeman, A.; Alves, M.; Williams, J.

    1993-01-01

    The Alaska SAR Facility has been receiving and processing SAR data from the J-ERS-1 satellite since Spring 1992. Corner reflectors have been set up for J-ERS-1 SAR calibration at a site near Delta Junction, in central Alaska. Image quality and calibration analysis results from the Delta Junction site and others will be presented in this paper. The impact of the 3-bit Analog-to-Digital Converter and the automatic stepping of the gain as a function of range in the J-ERS-1 radar receiver on calibration performance has been assessed. Preliminary observations on J-ERS-1 SAR data are that the average Signal-to-Noise ratio is generally fairly low, in the range 5-6dB. Azimuth ambiguity levels are higher than preflight analysis indicated. Over land, the dynamic range in the backscatter at L-band for approximately 36 degree incidence angle is often fairly high.

  8. Calibration Results for J-ERS-1 SAR Data Produced by the Alaska SAR Facility

    NASA Technical Reports Server (NTRS)

    Freeman, A.; Alves, M.; Williams, J.

    1993-01-01

    The Alaska SAR Facility has been receiving and processing SAR data from the J-ERS-1 satellite since Spring 1992. Corner reflectors have been set up for J-ERS-1 SAR calibration at a site near Delta Junction, in central Alaska. Image quality and calibration analysis results from the Delta Junction site and others will be presented in this paper. The impact of the 3-bit Analog-to-Digital Converter and the automatic stepping of the gain as a function of range in the J-ERS-1 radar receiver on calibration performance has been assessed. Preliminary observations on J-ERS-1 SAR data are that the average Signal-to-Noise ratio is generally fairly low, in the range 5-6 dB. Azimuth ambiguity levels are higher than preflight analysis indicated. Over land, the dynamic range in the backscatter at L-band for approximately 36 degree incidence angle is often fairly high...

  9. Si:Er-based light emitting diodes grown with sublimation MBE technique for optoelectronic applications

    NASA Astrophysics Data System (ADS)

    Shmagin, Viacheslav B.; Remizov, Dmitry Y.; Kuznetsov, Viktor P.; Shabanov, Vladimir N.; Krasilnik, Zakhary F.

    2006-02-01

    We examine here various types of Si:Er-based light emitting diodes (LEDs) grown with an original Sublimation MBE technique and radiating at 1.54 microns under p-n junction breakdown. It is concluded that p-n junction breakdown mechanism is the most effective way to control Er-related EL in reverse biased LEDs. Maximal Er-related EL intensity and excitation efficiency at room temperature are achieved in LEDs operating under mixed breakdown regime where tunnel and avalanche breakdown mechanisms present equally. The effective excitation cross section and the lifetime of excited Er 3+, the internal quantum efficiency and the thickness of the "dark" region are measured for SMBE grown LEDs radiating under mixed p-n junction breakdown.

  10. Touché! STARD3 and STARD3NL tether the ER to endosomes.

    PubMed

    Wilhelm, Léa P; Tomasetto, Catherine; Alpy, Fabien

    2016-04-15

    Membrane contact sites (MCSs) are subcellular regions where the membranes of distinct organelles come into close apposition. These specialized areas of the cell, which are involved in inter-organelle metabolite exchange, are scaffolded by specific complexes. STARD3 [StAR (steroidogenic acute regulatory protein)-related lipid transfer domain-3] and its close paralogue STARD3NL (STARD3 N-terminal like) are involved in the formation of contacts between late-endosomes and the endoplasmic reticulum (ER). The lipid transfer protein (LTP) STARD3 and STARD3NL, which are both anchored on the limiting membrane of late endosomes (LEs), interact with ER-anchored VAP [VAMP (vesicle-associated membrane protein)-associated protein] (VAP-A and VAP-B) proteins. This direct interaction allows ER-endosome contact formation. STARD3 or STARD3NL-mediated ER-endosome contacts, which affect endosome dynamics, are believed to be involved in cholesterol transport. PMID:27068960

  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. 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.

  13. 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.

  14. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... date on which he or she became disabled; or (2) Remarried before attaining age 60, but is now unmarried... now unmarried. (b) Reentitlement. A claimant will have the relationship of a remarried widow(er) if...

  15. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... date on which he or she became disabled; or (2) Remarried before attaining age 60, but is now unmarried... now unmarried. (b) Reentitlement. A claimant will have the relationship of a remarried widow(er) if...

  16. Ab initio study of intrinsic, H and He point defects in hcp-Er

    SciTech Connect

    Yang, Li; Peng, SM; Long, XG; Gao, Fei; Heinisch, Howard L.; Kurtz, Richard J.; Zu, Xiaotao T.

    2010-03-01

    Ab initio calculations based on density functional theory have been performed to determine the properties of self-interstitial atoms (SIAs), vacancies, and single H and He atoms in hcp-Er. The results show that the most stable configuration for an SIA is a basal octahedral (BO) configuration, while the octahedral (O), basal split (BS) and crowdion (C) interstitial configurations are less stable, followed by the split <0001> dumbbell and tetrahedral configurations. For both H and He defects, the formation energy of an interstitial atom is less than that of a substitutional atom in hcp-Er. Furthermore, the tetrahedral interstitial position is more stable than an octahedral position for both He and H interstitials. The hybridization of the He and H defects with Er atoms has been used to explain the relative stabilities of these defects in hcp-Er.

  17. Luminescent Enhancement in Mg- and Er-Codoped LiNbO3 Crystals

    NASA Astrophysics Data System (ADS)

    Tang, Li-Qin; Zhao, Li-Juan; Zhang, Xin-Zheng; Yu, Hua; Meng, Jie; Liang, Qin; Xu, Jing-Jun; Kong, Yong-Fa

    2005-03-01

    We investigate the MgO codoping-induced effect on the luminescent properties of Er3+-doped and Er/Mg codoped LiNbO3 crystals. The emission and excitation spectra and the absorption spectra are measured. The results show that the luminescent behaviour of Er3+ ions is very sensitive to the codoping of Mg2+ ions. According to the photorefractive level theory, we propose a quench model for the Er/Mg codoped lithium niobate crystal. The quench centres are suggested to be the bipolaron (NbLi-NbNb), we attribute the luminescent enhancement to the decreasing concentration of these centres. The luminescent enhancement effect is successfully explained.

  18. Spectroscopic properties of Er3+ doped lead phosphate glasses for photonic application 4-23-2009

    SciTech Connect

    Santos, C. C.; Guedes, I.; Moura, A. L. Moura; de Araujo, M. T.; Jacinto, C.; Vermelho, M. V. D.; Loong, C. K.; Boatner, Lynn A

    2010-01-01

    The spectroscopic characteristics of Er3+-doped lead phosphate glasses have been investigated, and Judd-Ofelt analysis was used to evaluate the effect of increasing the Er3+ content on the glass matrices. The intensity-dependent Judd=-Ofelt parameters: (4) and (6) remained constant while (2) decreased. Photoluminescence analysis revealed a low up-conversion efficiency through the weak green (530 and 550 nm) and red (660 nm) signals that were present under excitation at 800 nm. The concentration quenching effect on the lifetime of the Er3+: 4I13/2 4I15/2 (1530 nm) transition is also evaluated as a result of the addition of Er3+ to the lead phosphate glass composition. The observed relatively large reduction in the lifetime reflects the significant effects of non-radiative processes in this system. The potential use of these glasses as photonic devices is also discussed.

  19. 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 apoE–ApoER2 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 monocyte–endothelial 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

  20. Nanoscale evidence of erbium clustering in Er-doped silicon-rich silica

    PubMed Central

    2013-01-01

    Photoluminescence spectroscopy and atom probe tomography were used to explore the optical activity and microstructure of Er3+-doped Si-rich SiO2 thin films fabricated by radio-frequency magnetron sputtering. The effect of post-fabrication annealing treatment on the properties of the films was investigated. The evolution of the nanoscale structure upon an annealing treatment was found to control the interrelation between the radiative recombination of the carriers via Si clusters and via 4f shell transitions in Er3+ ions. The most efficient 1.53-μm Er3+ photoluminescence was observed from the films submitted to low-temperature treatment ranging from 600°C to 900°C. An annealing treatment at 1,100°C, used often to form Si nanocrystallites, favors an intense emission in visible spectral range with the maximum peak at about 740 nm. Along with this, a drastic decrease of 1.53-μm Er3+ photoluminescence emission was detected. The atom probe results demonstrated that the clustering of Er3+ ions upon such high-temperature annealing treatment was the main reason. The diffusion parameters of Si and Er3+ ions as well as a chemical composition of different clusters were also obtained. The films annealed at 1,100°C contain pure spherical Si nanocrystallites, ErSi3O6 clusters, and free Er3+ ions embedded in SiO2 host. The mean size and the density of Si nanocrystallites were found to be 1.3± 0.3 nm and (3.1± 0.2)×1018 Si nanocrystallites·cm−3, respectively. The density of ErSi3O6 clusters was estimated to be (2.0± 0.2)×1018 clusters·cm−3, keeping about 30% of the total Er3+ amount. These Er-rich clusters had a mean radius of about 1.5 nm and demonstrated preferable formation in the vicinity of Si nanocrystallites. PMID:23336324

  1. Research on laser diode end-pumped Er:YSGG/YSGG composited crystal at 2.79 μm

    NASA Astrophysics Data System (ADS)

    Shen, Benjian; Kang, Hongxiang; Jie, Liang; Peng, Chen; Fu, Huaixiu

    2014-12-01

    Lasers at 2.79 μm emitted by Er:YSGG crystal have attracted considerable interest in biological and medical applications. However, due to the thermal effect of laser crystal, the output power has been limited. In this paper, the advantages of Er:YSGG/YSGG composite crystal in reducing thermal effects and achieving high output power are investigated theoretically and experimentally. The numerical results show that the temperature rising and total thermal deformation of Er:YSGG/YSGG composite crystal are evidently reduced because the undoped YSGG absorbs the heat generated from the Er:YSGG. The maximum temperature rising reduces with increasing of the length of undoped YSGG crystal, and its location moves from the pump face to the inside of the Er:YSGG. The optical path difference of the Er:YSGG/YSGG composite crystal is obviously reduced comparing with that of Er:YSGG crystal, which indicates the thermal focal length of the Er:YSGG/YSGG composite crystal is increased, and the thermal effects are reduced. In experiments, the maximum continuous wave output power of 900 mW with slope efficiency of 12.1% at wavelength of 2.79 μm is obtained in laser diode end pumped Er:YSGG/YSGG crystal. To our knowledge, the output power of Er:YSGG/YSGG crystal is the highest value for the laser diode end pumped Er:YSGG crystal. The thermal focal length of the Er:YSGG/YSGG measured in experiment is increased comparing with that of Er:YSGG. Investigations have demonstrated that the Er:YSGG/YSGG composite crystal has a great advantage in reducing the influence of thermal effects and achieving high output power.

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

    PubMed Central

    Papoutsopoulou, Stamatia; Janknecht, Ralf

    2000-01-01

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

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

    PubMed

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

    2010-05-01

    Increase in cytosolic calcium concentration ([Ca2+](c)), release of endoplasmic reticulum (ER) calcium ([Ca2+](er)) and ER stress have been proposed to be involved in oxidative toxicity. Nevertheless, their relative involvements in the processes leading to cell death are not well defined. In this study, we investigated whether oxidative stress generated during ascorbate-driven menadione redox cycling (Asc/Men) could trigger these three events, and, if so, whether they contributed to Asc/Men cytoxicity in MCF-7 cells. Using microspectrofluorimetry, we demonstrated that Asc/Men-generated oxidative stress was associated with a slow and moderate increase in [Ca2+](c), largely preceding permeation of propidium iodide, and thus cell death. Asc/Men treatment was shown to partially deplete ER calcium stores after 90 min (decrease by 45% compared to control). This event was associated with ER stress activation, as shown by analysis of eIF2 phosphorylation and expression of the molecular chaperone GRP94. Thapsigargin (TG) was then used to study the effect of complete [Ca2+](er) emptying during the oxidative stress generated by Asc/Men. Surprisingly, the combination of TG and Asc/Men increased ER stress to a level considerably higher than that observed for either treatment alone, suggesting that [Ca2+](er) release alone is not sufficient to explain ER stress activation during oxidative stress. Finally, TG-mediated [Ca2+](er) release largely potentiated ER stress, DNA fragmentation and cell death caused by Asc/Men, supporting a role of ER stress in the process of Asc/Men cytotoxicity. Taken together, our results highlight the involvement of ER stress and [Ca2+](er) decrease in the process of oxidative stress-induced cell death in MCF-7 cells. PMID:20006589

  4. Monitoring cytosolic and ER Zn(2+) in stimulated breast cancer cells using genetically encoded FRET sensors.

    PubMed

    Hessels, Anne M; Taylor, Kathryn M; Merkx, Maarten

    2016-02-17

    The Zn(2+)-specific ion channel ZIP7 has been implicated to play an important role in releasing Zn(2+) from the ER. External stimulation of breast cancer cells has been proposed to induce phosphorylation of ZIP7 by CK2α, resulting in ZIP7-mediated Zn(2+) release from the ER into the cytosol. Here, we examined whether changes in cytosolic and ER Zn(2+) concentrations can be detected upon such external stimuli. Two previously developed FRET sensors for Zn(2+), eZinCh-2 (Kd = 1 nM at pH 7.1) and eCALWY-4 (Kd = 0.63 nM at pH 7.1), were expressed in both the cytosol and the ER of wild-type MCF-7 and TamR cells. Treatment of MCF-7 and TamR cells with external Zn(2+) and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn(2+) in both cytosol and ER, suggesting that Zn(2+) was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, EGF/ionomycin, showed no changes in intracellular Zn(2+) levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and ER Zn(2+), nor in experiments in which cytosolic and ER Zn(2+) were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that EGF-ionomycin treatment does not result in significant changes in cytosolic Zn(2+) levels as a result from Zn(2+) release from the ER. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn(2+) dyes. PMID:26739447

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

    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 (ERα) 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

  6. Composite resin bond strength to primary dentin prepared with Er, Cr:YSSG laser.

    PubMed

    Sung, Eric C; Chenard, Torin; Caputo, Angelo A; Amodeo, Michael; Chung, Evelyn M; Rizoiu, Ioana M

    2005-01-01

    This in vitro study evaluated the shear bond strength of a hybrid composite resin bonded to primary dentin prepared with an Er, Cr:YSGG hydrokinetic laser compared to conventional bur prepared primary dentin. The results suggest that primary dentin surfaces treated with the Er, Cr:YSGG laser, with or without etching, may provide comparable or increased composite resin bond strengths depending upon bonding agent used. PMID:16302599

  7. 20 CFR 218.44 - When a remarried 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 remarried widow(er) annuity ends. 218.44 Section 218.44 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ANNUITY BEGINNING AND ENDING DATES When an Annuity Ends § 218.44 When a remarried widow(er) annuity ends. (a) Entitlement based on age....

  8. 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 μm 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, O₂ and N₂, have been investigated. It was found that only in O₂ the Bi³⁺ 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 Bi⁰ metallic nanoparticles that are deleterious non radiative channels for Er luminescence, efficient energy transfer from Bi to Er has been obtained only in O₂. It is due to the excitation of ultraviolet broad Bi₃⁺ 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 μm 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 μm.

  9. ER stress affects processing of MHC class I-associated peptides

    PubMed Central

    Granados, Diana P; Tanguay, Pierre-Luc; Hardy, Marie-Pierre; Caron, tienne; de Verteuil, Danielle; Meloche, Sylvain; Perreault, Claude

    2009-01-01

    Background Viral infection and neoplastic transformation trigger endoplasmic reticulum (ER) stress. Thus, a large proportion of the cells that must be recognized by the immune system are stressed cells. Cells respond to ER stress by launching the unfolded protein response (UPR). The UPR regulates the two key processes that control major histocompatibility complex class I (MHC I)-peptide presentation: protein synthesis and degradation. We therefore asked whether and how the UPR impinges on MHC I-peptide presentation. Results We evaluated the impact of the UPR on global MHC I expression and on presentation of the H2Kb-associated SIINFEKL peptide. EL4 cells stably transfected with vectors coding hen egg lysozyme (HEL)-SIINFEKL protein variants were stressed with palmitate or exposed to glucose deprivation. UPR decreased surface expression of MHC I but did not affect MHC I mRNA level nor the total amount of intracellular MHC I proteins. Impaired MHC I-peptide presentation was due mainly to reduced supply of peptides owing to an inhibition of overall protein synthesis. Consequently, generation of H2Kb-SIINFEKL complexes was curtailed during ER stress, illustrating how generation of MHC I peptide ligands is tightly coupled to ongoing protein synthesis. Notably, the UPR-induced decline of MHC I-peptide presentation was more severe when the protein source of peptides was localized in the cytosol than in the ER. This difference was not due to changes in the translation rates of the precursor proteins but to increased stability of the cytosolic protein during ER stress. Conclusion Our results demonstrate that ER stress impairs MHC I-peptide presentation, and that it differentially regulates expression of ER- vs. cytosol-derived peptides. Furthermore, this work illustrates how ER stress, a typical feature of infected and malignant cells, can impinge on cues for adaptive immune recognition. PMID:19220912

  10. The SR/ER-mitochondria calcium crosstalk is regulated by GSK3? during reperfusion injury.

    PubMed

    Gomez, L; Thiebaut, P-A; Paillard, M; Ducreux, S; Abrial, M; Crola Da Silva, C; Durand, A; Alam, M R; Van Coppenolle, F; Sheu, S-S; Ovize, M

    2016-02-01

    Glycogen synthase kinase-3? (GSK3?) is a multifunctional kinase whose inhibition is known to limit myocardial ischemia-reperfusion injury. However, the mechanism mediating this beneficial effect still remains unclear. Mitochondria and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. We questioned here whether GSK3? might have a role in the Ca(2+) transfer from SR/ER to mitochondria at reperfusion. We showed that a fraction of GSK3? protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs) in the heart, and that GSK3? specifically interacted with the inositol 1,4,5-trisphosphate receptors (IP3Rs) Ca(2+) channeling complex in MAMs. We demonstrated that both pharmacological and genetic inhibition of GSK3? decreased protein interaction of IP3R with the Ca(2+) channeling complex, impaired SR/ER Ca(2+) release and reduced the histamine-stimulated Ca(2+) exchange between SR/ER and mitochondria in cardiomyocytes. During hypoxia reoxygenation, cell death is associated with an increase of GSK3? activity and IP3R phosphorylation, which leads to enhanced transfer of Ca(2+) from SR/ER to mitochondria. Inhibition of GSK3? at reperfusion reduced both IP3R phosphorylation and SR/ER Ca(2+) release, which consequently diminished both cytosolic and mitochondrial Ca(2+) concentrations, as well as sensitivity to apoptosis. We conclude that inhibition of GSK3? at reperfusion diminishes Ca(2+) leak from IP3R at MAMs in the heart, which limits both cytosolic and mitochondrial Ca(2+) overload and subsequent cell death. PMID:26206086

  11. Magnetic Properties of RB66 (R = Gd, Tb, Ho, Er, and Lu)

    SciTech Connect

    Kim, Hyunsoo; Budko, Serguei; ATanatar, Makariy; Avdashchenko, D.V.; Matovnikov, A.V.; Mitroshenkov, N.V.; Novikov, V.V.; Prozorov, Ruslan

    2012-05-17

    We report magnetic susceptibility measurements of RB66 (R = Gd, Tb, Ho, Er, and Lu) boron-rich rare earth containing borides down to 50 mK. The data suggest a spin glass low temperature state for RB66 (R = Gd, Tb, Ho, and Er) with the freezing temperatures below 1 K. The magnetic properties appear to be influenced by the anisotropy of the magnetic moments, probably via the crystalline electric field effects.

  12. Er:YAG laser for the surgical treatment of the carpal tunnel syndrome

    NASA Astrophysics Data System (ADS)

    Russ, Detlef; Ebinger, Thomas; Illich, Wolfgang; Steiner, Rudolf W.

    2003-10-01

    We developed a new surgical procedure to improve the recurrence rate using an Er:YAG laser as dissection tool for the carpal ligament with the objective to ablate a small amount of the carpal ligament and to denaturate its ends. The Er:YAG Laser was transmitted to the applicator via a GeO fiber. With this system we proceeded 10 carpal ligament dissections without any complications in the follow-up period. All patients were free of pain and recurrence.

  13. Completion Report for Well ER-EC-7

    SciTech Connect

    Bechtel Nevada

    2004-10-01

    Well ER-EC-7 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 the summer of 1999 as part of the Department of Energy's hydrogeologic investigation 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 a depth of 265.8 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 422.5 meters. The planned depth of 762 meters was not reached due to borehole stability problems. One completion string with two isolated slotted intervals was installed in the well. A preliminary composite, static, water level was measured at the depth of 227.8 meters, 20 days after installation of the completion string. Detailed lithologic descriptions with stratigraphic assignments are included in the report. These are based on composite drill cuttings, supplemented by geophysical log data, and incorporating data from detailed chemical and mineralogical studies of rock samples. Beneath a thin alluvial deposit, the well penetrated 410 meters of lava and bedded tuff of the Volcanics of Fortymile Canyon Group, deposited in the Timber Mountain caldera moat after caldera collapse. The geologic interpretation of data from this well provides information on the thickness, lithologic composition, and hydrogeologic character of moat-filling rocks in the southern portion of the Timber Mountain caldera complex in the southwestern Nevada volcanic field.

  14. Completion Report for Well ER-12-2

    SciTech Connect

    Bechtel Nevada

    2004-11-01

    Well ER-12-2 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. The well was drilled from November 2002 to January 2003 as part of a hydrogeologic investigation program for the Yucca Flat Corrective Action Unit. The overall purpose of the well was to gather subsurface data to better characterize the hydrogeology in the northwestern portion of Yucca Flat. The well was drilled to total measured depth of 2,097.9 meters. The 131.1-centimeter-diameter borehole was left open (i.e., uncased) below the base of the intermediate casing at 901.6 meters. A piezometer string was installed outside the surface casing to a depth of 176.4 meters to monitor a zone of perched water. Data gathered during and shortly after hole construction include composite drill cuttings samples collected every 3 meters, sidewall core samples from 7 depths, various geophysical logs, and water level measurements. These data indicate that the well penetrated, in descending order, 137.5 meters of Quaternary and Tertiary alluvium, 48.8 meters of Tertiary volcanic rocks, 289.6 meters of Mississippian Chainman Shale, and 1,622.5 meters of Mississippian and Upper Devonian Eleana Formation consisting of shale, argillite, sandstone, quartzite, and limestone. Forty-seven days after the well was drilled the water level inside the main hole was tagged at the depth of 65.43 meters, and the water level inside the piezometer string was tagged at 127.14 meters.

  15. Completion Report for Well ER-EC-2A

    SciTech Connect

    M. J. Townsend

    2002-03-01

    Well ER-EC-2A was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations 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 of 2000 as part of a hydrogeologic investigation program in the Pahute Mesa - Oasis Valley region just west of the Nevada Test Site. A 44.5-centimeter surface hole was drilled and cased off to a depth of 412.9 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 1,516.1 meters. One completion string with three isolated slotted intervals was installed in the well. A preliminary composite, static water level was measured at the depth of 228.0 meters, approximately two months after installation of the completion string. Detailed lithologic descriptions with preliminary stratigraphic assignments are included in this report. These are based on composite drill cuttings collected every 3 meters, and 81 sidewall samples taken at various depths below 212 meters, supplemented by geophysical log data. Detailed petrographic, chemical, and mineralogical studies of rock samples were conducted on 30 samples. The well was collared in rhyolite lava and penetrated Tertiary-age lava and tuff of the Volcanics of Fortymile Canyon and the Timber Mountain Group. The preliminary geologic interpretation of borehole data indicates that this well was drilled within the margins of the buried Rainier Mesa and Ammonia Tanks calderas, and that caldera collapse in this area was deeper than expected, resulting in a section of Volcanics of Fortymile Canyon (caldera-filling deposit) that is much thicker than expected.

  16. Completion Report for Well ER-EC-4

    SciTech Connect

    M. J. Townsend

    2000-09-01

    Well ER-EC-4 was drilled for the US 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 summer 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 a depth of 263.7 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 1,062.8 meters. One completion string with three isolated slotted intervals was installed in the well. A preliminary composite, static, water level was measured at the depth of 228.3 meters, two months after installation of the completion string. Detailed lithologic descriptions with preliminary stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters, and 35 sidewall samples taken at various depths below 286.5 meters, supplemented by geophysical log data. Detailed chemical and mineralogical studies of rock samples are in progress. The well was collared in basalt and penetrated Tertiary-age lava and tuff of the Thirsty Canyon Group, the Volcanics of Fortymile Canyon, and the Timber Mountain Group. The preliminary geologic interpretation of data from this well helps pinpoint the location of the western margin of the Timber Mountain caldera complex in the southern Nevada volcanic field.

  17. Completion report for Well ER-EC-6

    SciTech Connect

    M. J. Townsend

    2000-05-01

    Well ER-EC-6 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 DOE's hydrogeologic investigation well program in the Western Pahute Mesa - Oasis Valley region just west of the Nevada Test Site. A 66-centimeter surface hole was drilled and cased off to the depth of 485.1 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 434.6 meters prior to installation of the completion string. One completion string with four 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 33 sidewall samples taken at various depths below 504.4 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, and the Volcanics of Quartz Mountain. Intense hydrothermal alteration was observed below the depth of 640 m. The preliminary geologic interpretation indicates that this site may be located on a buried structural ridge that separates the Silent Canyon and Timber Mountain caldera complexes.

  18. Completion Report for Well ER-EC-5

    SciTech Connect

    Bechtel Nevada

    2004-10-01

    Well ER-EC-5 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 the summer of 1999 as part of the U.S. Department of Energy's hydrogeologic investigation program in the Western Pahute Mesa - Oasis Valley region just west of the Nevada Test Site. A 44.5-centimeter surface hole was drilled and cased off to a depth of 342.6 meters below ground surface. The borehole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 762.0 meters. One completion string with three isolated slotted intervals was installed in the well. A preliminary composite, static water level was measured at the depth of 309.9 meters, 40 days after installation of the completion string. Detailed lithologic descriptions with stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters, and 18 sidewall samples taken at various depths below 349.6 meters, supplemented by geophysical log data and results from detailed chemical and mineralogical analyses of rock samples. The well penetrated Tertiary-age tuffs of the Thirsty Canyon Group, caldera moat-filling sedimentary deposits, lava of the Beatty Wash Formation, and landslide breccia and tuffs of the Timber Mountain Group. The well reached total depth in welded ashflow tuff of the Ammonia Tanks Tuff after penetrating 440.1 meters of this unit, which is also the main water-producing unit in the well. The geologic interpretation of data from this well constrains the western margin of the Ammonia Tanks caldera to the west of the well location.

  19. Xenoestrogens alter estrogen receptor (ER) α intracellular levels.

    PubMed

    La Rosa, Piergiorgio; Pellegrini, Marco; Totta, Pierangela; Acconcia, Filippo; Marino, Maria

    2014-01-01

    17β-estradiol (E2)-dependent estrogen receptor (ER) α intracellular concentration is a well recognized critical step in the pleiotropic effects elicited by E2 in several target tissues. Beside E2, a class of synthetic and plant-derived chemicals collectively named endocrine disruptors (EDs) or xenoestrogens bind to and modify both nuclear and extra-nuclear ERα activities. However, at the present no information is available on the ability of EDs to hamper ERα intracellular concentration. Here, the effects of bisphenol A (BPA) and naringenin (Nar), prototypes of synthetic and plant-derived ERα ligands, have been evaluated on ERα levels in MCF-7 cells. Both EDs mimic E2 in triggering ERα Ser118 phosphorylation and gene transcription. However, only E2 or BPA induce an increase of cell proliferation; whereas 24 hrs after Nar stimulation a dose-dependent decrease in cell number is reported. E2 or BPA treatment reduces ERα protein and mRNA levels after 24 hrs. Contrarily, Nar stimulation does not alter ERα content but reduces ERα mRNA levels like other ligands. Co-stimulation experiments indicate that 48 hrs of Nar treatment prevents the E2-induced ERα degradation and hijacks the physiological ability of E2:ERα complex to regulate gene transcription. Mechanistically, Nar induces ERα protein accumulation by preventing proteasomal receptor degradation via persistent activation of p38/MAPK pathway. As a whole these data demonstrate that ERα intracellular concentration is an important target through which EDs hamper the hormonal milieu of E2 target cells driving cells to different outcomes or mimicking E2 even in the absence of the hormone. PMID:24586459

  20. Completion Report for Well ER-EC-8

    SciTech Connect

    Bechtel Nevada

    2004-10-01

    Well ER-EC-8 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 the summer of 1999 as part of the U.S. Department of Energy's hydrogeologic investigation program in the Western Pahute Mesa - Oasis Valley region just west of the Nevada Test Site. A 44.5-centimeter surface hole was drilled and cased off to a depth of 129.8 meters below the surface. The hole diameter was then decreased to 31.1 centimeters for drilling to a total depth of 609.6 meters. One completion string with three isolated slotted intervals was installed in the well. A preliminary composite, static water level was measured at the depth of 98.4 meters, 24 days after installation of the completion string. Detailed lithologic descriptions with stratigraphic assignments are included in the report. These are based on evaluation of composite drill cuttings collected every 3 meters, and 20 sidewall samples taken at various depths below 157.9 meters, supplemented by geophysical log data and results of detailed chemical and mineralogical studies of rock samples. Drilling began in Tertiary-age tuff of the Thirsty Canyon Group, and penetrated tuffs of the Beatty Wash Formation, tuff of Buttonhook Wash, and the upper portion of the Ammonia Tanks Tuff. The geologic interpretation of data from this well helps define the location of the western margin of the Timber Mountain caldera complex in the southwestern Nevada volcanic field. Geologic and hydrologic data from the well will aid in development of models to predict groundwater flow and contaminant migration within and near the Nevada Test Site.

  1. Wavelength tunable Er-Yb double-clad fiber laser

    NASA Astrophysics Data System (ADS)

    Ibarra-Escamilla, Baldemar; Kuzin, Evgeny A.; Pottiez, Olivier; Haus, Joseph W.; Powers, Peter E.; Zhan, Qiwen

    2010-05-01

    Wavelength-tunable sources are important for applications such as fiber optics sensing, medical instrumentation, and optical communication. A tunable source design can use a Fabry-Perot (FP) cavity configuration with a tunable filter inserted into the system. In this work we experimentally demonstrated a wavelength-tunable fiber laser by the use of a PM-Er:Yb double-clad fiber placed in a FP cavity formed by two Dichroic Mirrors (DM). Our pump laser wavelength was 976 nm and the maximal output power from this laser that we can introduce to the fiber was 20 W. To get wavelength tunability we included a Diffractive Grating (DG) with 600 l/mm in our laser cavity. The zero order reflection from the DG is the output coupler and the first order diffracted beam is reflected back into the fiber using a DM. We included a half-wave plate and a polarizer in the cavity to increase the stability of the continuous wave laser operation and also to impose a linear polarization at the laser output. With this configuration we can tune the wavelength from 1535 to 1567 nm by rotating a DM at a rate of 0.02 degrees/nm. With our configuration wide tunability was possible only when we used fiber lengths between 2.5 and 3.6 m. The maximal output power was 850 mW using 3.6 m of fiber length. We believe that a Q-switched extension of this source can be used in nonlinear optics applications, such as Terahertz generation.

  2. ERS-ENVISAT radar altimetry over the Amazon basin

    NASA Astrophysics Data System (ADS)

    Santos da Silva, J.; Calmant, S.; Rotunno Filho, O. C.; Seyler, F.; Mansur, W. J.; Cochonneau, G.

    2009-12-01

    Since the launch of satellite embarking radar altimeters in the late 80’s, scientists have investigated the feasibility of using these ocean-dedicated data over the continental waters. In fact, satellite radar altimetry is being recognized as a powerful tool to obtain time series of water stage consistent to those obtained by conventional in situ gauge stations. In addition, this technology has been proved to provide reliable information about the dynamics of large water bodies such as lakes and inner seas. However, the results should be deeply examined as we shift the analysis to water levels acquired during satellite crosses over rivers. Yet, hydrologists are still reluctant in using these data, as neither the neces¬sary time sampling nor accuracy is achieved, leading to endless debates in specialized workshops. Noteworthy to highlight, few published studies are dedicated to an in depth assessment of the radar altimetry over rivers, in¬cluding comparisons with water levels at fluviometric gauges. In this work, we present an extensive analysis of the quality of times series of river stages that we have constructed in the Amazon basin for a variety of water bodies such as large rivers, narrow stems, lakes and flooded areas using radar altimeters embarked on¬board ERS-2 and ENVISAT. The approach includes the sensitivity to the raw data processing methodology such as the tracking algorithm, the data selection at the crossings between satellite track and river bed (so-called virtual stations) and correction for off-nadir effects. The VALS toolbox was developed to process altimetry data at virtual stations under the framework of this study. Results of internal validation at cross-overs and external validation by comparison with in situ gauges are presented.

  3. Control of radiation heat transfer through a composite window featuring ER fluid: A conceptual investigation

    SciTech Connect

    Zhang, C.; Lloyd, J.R.

    1994-08-01

    Radiation heat transfer control through the application of an electric field upon an Electrorheological (ER) fluid based composite material is an innovative new area of research. A conceptual experiment has been conducted to study radiation heat transfer through a composite window featuring an ER fluid. The composite window is composed of two thin glass plates with a layer of ER fluid contained between them. The glass walls were transparent except for a very thin coating of an electric-conductive film which enabled the inside of the glass surfaces to serve as electrodes. The ER fluid was contained between the glass surfaces and consisted of a suspension of micron sized crystalline zeolite particles in a silicon oil. This study has demonstrated the unique capability of ER fluids to regulate and control radiation heat transfer via transmittance measurements. A semi-empirical model is developed from the experimental data to correlate the dependence of radiation transmission through ER fluids based on several physical parameters (f{sub v}, V, and L). This model agrees reasonably well with the measured data. The results obtained in this study are very important to those concerned with the development of a thermally smart material for heat transfer control.

  4. Er:YAG clinical experience in Japan: a review of scientific investigations

    NASA Astrophysics Data System (ADS)

    Aoki, Akira; Watanabe, Hisashi; Ishikawa, Isao

    1998-04-01

    An Er:YAG laser apparatus with a contact fiberoptic delivery system has been newly developed in Japan and its clinical use was approved by the Ministry of Health and Welfare in 1995. Previous investigations using the laser apparatus and its prototype showed that the Er:YAG laser was able to effectively ablate dental hard and soft tissues without major thermal damage, and that the influence on the tooth pulp was minimal. The degree of damage to the surrounding tissues caused by the inadvertent irradiation has also been evaluated. Bactericidal effect of the Er:YAG laser has been shown. The utility and safety of the Er:YAG laser treatment for caries removal and cavity preparation, soft tissue minor surgery, and scaling have been revealed by several clinical studies. Reports describing the usefulness of the Er:YAG laser are increasing. However, further studies are required in order to clarify the advantages and limitations of the Er:YAG laser treatment and to establish a reliable procedure.

  5. Electrical Conductivity of Er2O3-Doped c-ZrO2 Ceramics

    NASA Astrophysics Data System (ADS)

    Aktas, Bulent; Tekeli, Suleyman; Kucuktuvek, Mustafa

    2014-01-01

    The effect of Er2O3 addition on electrical conductivity of c-ZrO2 was investigated by analyzing the impedance spectra of undoped and various amounts of Er2O3-doped cubic zirconia (c-ZrO2). The undoped and 1-15 wt% Er2O3-doped c-ZrO2 powders were prepared via colloidal process. The doped powders were then pelletized under a pressure of 200 MPa. In addition, the undoped and Er2O3-doped c-ZrO2 specimens were sintered at 1500 °C for 1 h. The electrical conductivity of the specimens was measured using a frequency response analyzer in the frequency range of 100 mHz-13 MHz, in the temperature range of 300-800 °C. Electrical conductivity results indicate an increase in the conductivity with increase in the test temperature. The addition of 1 wt% Er2O3 into c-ZrO2 led to an increase in the grain interior, grain boundary, and total conductivities. The distortion caused by the addition of Er3+ cations in the c-ZrO2 lattice leads to an increase in the concentration of oxygen vacancies in the c-ZrO2 matrix, resulting in an enhancement in the electrical conductivities.

  6. Excellent ethanol sensing properties based on Er2O3-Fe2O3 nanotubes

    NASA Astrophysics Data System (ADS)

    Liu, Chang-Bai; He, Ying; Wang, Sheng-Lei

    2015-11-01

    In this work, pure α-Fe2O3 and Er2O3-Fe2O3 nanotubes were synthesized by a simple single-capillary electrospinning technology followed by calcination treatment. The morphologies and crystal structures of the as-prepared samples were characterized by scanning electron microscopy and x-ray diffraction, respectively. The gas-sensing properties of the as-prepared samples have been researched, and the result shows that the Er2O3-Fe2O3 nanotubes exhibit much better sensitivity to ethanol. The response value of Er2O3-Fe2O3 nanotubes to 10 ppm ethanol is 21 at the operating temperature 240°, which is 14 times larger than that of pure α-Fe2O3 nanotubes (response value is 1.5). The ethanol sensing properties of α-Fe2O3 nanotubes are remarkably enhanced by doping Er, and the lowest detection limit of Er2O3-Fe2O3 nanotubes is 300 ppb, to which the response value is about 2. The response and recovery times are about 4 s and 70 s to 10 ppm ethanol, respectively. In addition, the Er2O3-Fe2O3 nanotubes possess good selectivity and long-term stability. Project supported by Jilin Provincial Science and Technology Department, China (Grant No. 20140204027GX) and the Challenge Cup for College Students, China (Grant No. 450060497053).

  7. Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells

    PubMed Central

    Mujumdar, Nameeta; Banerjee, Sulagna; Chen, Zhiyu; Sangwan, Veena; Chugh, Rohit; Dudeja, Vikas; Yamamoto, Masato; Vickers, Selwyn M.

    2014-01-01

    Pancreatic cancer is a devastating disease with a survival rate of <5%. Moreover, pancreatic cancer aggressiveness is closely related to high levels of prosurvival mediators, which can ultimately lead to rapid disease progression. One of the mechanisms that enables tumor cells to evade cellular stress and promote unhindered proliferation is the endoplasmic reticulum (ER) stress response. Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response (UPR). The UPR initially compensates for damage, but it eventually triggers cell death if ER dysfunction is severe or prolonged. Triptolide, a diterpene triepoxide, has been shown to be an effective compound against pancreatic cancer. Our results show that triptolide induces the UPR by activating the PKR-like ER kinase-eukaryotic initiation factor 2α axis and the inositol-requiring enzyme 1α-X-box-binding protein 1 axis of the UPR and leads to chronic ER stress in pancreatic cancer. Our results further show that glucose-regulated protein 78 (GRP78), one of the major regulators of ER stress, is downregulated by triptolide, leading to cell death by apoptosis in MIA PaCa-2 cells and autophagy in S2-VP10 cells. PMID:24699326

  8. Proteomic mapping of ER-PM junctions identifies STIMATE as regulator of Ca2+ influx

    PubMed Central

    Jing, Ji; He, Lian; Sun, Aomin; Quintana, Ariel; Ding, Yuehe; Ma, Guolin; Tan, Peng; Liang, Xiaowen; Zheng, Xiaolu; Chen, Liangyi; Shi, Xiaodong; Zhang, Shenyuan L.; Zhong, Ling; Huang, Yun; Dong, Meng-Qiu; Walker, Cheryl L.; Hogan, Patrick G.; Wang, Youjun; Zhou, Yubin

    2015-01-01

    Specialized junctional sites that connect the plasma membrane (PM) and endoplasmic reticulum (ER) play critical roles in controlling lipid metabolism and Ca2+ signaling1–4. Store operated Ca2+ entry mediated by dynamic STIM1-ORAI1 coupling represents a classical molecular event occurring at ER-PM junctions, but the protein composition and how previously-unrecognized protein regulators facilitate this process remain ill-defined. Using a combination of spatially-restricted biotin-labelling in situ coupled with mass spectrometry5, 6 and a secondary screen based on bimolecular fluorescence complementation7, we mapped the proteome of intact ER-PM junctions in living cells without disrupting their architectural integrity. Our approaches lead to the discovery of an ER-resident multi-transmembrane protein that we call STIMATE (STIM-activating enhancer, encoded by TMEM110) as a positive regulator of Ca2+ influx in vertebrates. STIMATE physically interacts with STIM1 to promote STIM1 conformational switch. Genetic depletion of STIMATE substantially reduces STIM1 puncta formation at ER-PM junctions and suppresses the Ca2+-NFAT signaling. Our findings enable further genetic studies to elucidate the function of STIMATE in normal physiology and disease, and set the stage to uncover more uncharted functions of hitherto underexplored ER-PM junctions. PMID:26322679

  9. Mission planning for an Earth observation low Earth orbiter: ERS-1

    NASA Technical Reports Server (NTRS)

    Lockyer, Paul

    1993-01-01

    ERS-1, the first European Remote Sensing satellite, has a payload which consists primarily of microwave instruments and is in a polar sun-synchronous orbit. All ground and on-board activities from user requests to delivery of data products are combined into one integrated system. In view of the high number of products which can be generated by ERS-1, the Mission Planning System (MPS), which plans the on-board activities of ERS-1, is an essential tool for operations since manual planning of the large number of daily operations is out of the question. In addition the MPS, in line with the integrated nature of the ERS-1 system, also plans activities at the prime ground station, including among others, the operation of the payload data processing systems there. This paper outlines the operations concepts for ERS-1 mission planning, and describes the Mission Planning System used at the ERS-1 Control Center. Novel functionalities, such as automatic resource clash resolution, are described. A critical discussion gives lessons learned for future mission planning systems.

  10. The NASA Earth Research-2 (ER-2) Aircraft: A Flying Laboratory for Earth Science Studies

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    The National Aeronautics and Space Administration Dryden Flight Research Center, Edwards, California, has two Lockheed Martin Corporation (Bethesda, Maryland) Earth Research-2 (ER2) aircraft that serve as high-altitude and long-range flying laboratories. The ER-2 aircraft has been successfully 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 research missions for the ER-2 aircraft are planned, implemented, and managed by the Dryden Flight Research Center Science Mission Directorate. Maintenance and instrument payload integration is conducted by Dryden personnel. The ER-2 aircraft provides experimenters with a wide array of payload accommodations areas with suitable environment control with required electrical and mechanical interfaces. Missions may be flown out of Dryden or from remote bases worldwide, according to research requirements. The NASA ER-2 aircraft is utilized by a variety of customers, including U.S. Government agencies, civilian organizations, universities, and state governments. The combination of the ER-2 aircraft 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 and other customers.

  11. Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils

    SciTech Connect

    Binet, Francois; Chiasson, Sonia; Girard, Denis

    2010-01-01

    Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenic trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2{alpha} are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.

  12. TULP1 Missense Mutations Induces the Endoplasmic Reticulum Unfolded Protein Response Stress Complex (ER-UPR).

    PubMed

    Lobo, Glenn P; Ebke, Lindsey A; Au, Adrian; Hagstrom, Stephanie A

    2016-01-01

    Mutations in the TULP1 gene are associated with early-onset retinitis pigmentosa (RP); however, the molecular mechanisms related to the deleterious effects of TULP1 mutations remains unknown. Several studies have shown that misfolded proteins secondary to genetic mutations can accumulate within the endoplasmic reticulum (ER), causing activation of the unfolded protein response (UPR) complex followed by cellular apoptosis. We hypothesize that TULP1 mutations produce misfolded protein products that accumulate in the ER and induce cellular apoptosis via the UPR. To test our hypothesis, we first performed three in-silico analyses of TULP1 missense mutations (I459K, R420P and F491L), which predicted misfolded protein products. Subsequently, the three mutant TULP1-GFP constructs and wild-type (wt) TULP1-GFP were transiently transfected into hTERT-RPE-1 cells. Staining of cells using ER tracker followed by confocal microscopy showed wt-TULP1 localized predominantly to the cytoplasm and plasma membrane. In contrast, all three mutant TULP1 proteins revealed cytoplasmic punctate staining which co-localized with the ER. Furthermore, western blot analysis of cells expressing mutant TULP1 proteins revealed induction of downstream targets of the ER-UPR complex, including BiP/GPR-78, phosphorylated-PERK (Thr980) and CHOP. Our in-vitro analyses suggest that mutant TULP1 proteins are misfolded and accumulate within the ER leading to induction of the UPR stress response complex. PMID:26427415

  13. Broadband near-infrared emission from Tm3+/Er3+ co-doped nanostructured glass ceramics

    NASA Astrophysics Data System (ADS)

    Chen, Daqin; Wang, Yuansheng; Bao, Feng; Yu, Yunlong

    2007-06-01

    Transparent SiO2-Al2O3-NaF-YF3 glass ceramics co-doped with Er3+ and Tm3+ were prepared by melt quenching and subsequent heating. X-ray diffraction and transmission electron microscopy experiments revealed that β-YF3 nanocrystals incorporated with Er3+ and Tm3+ were precipitated homogeneously among the oxide glass matrix. An integrated broad near-infrared emission band in the wavelength region of 1300-1700 nm, consisting of Tm3+ emissions around 1472 nm (H34→F34) and 1626 nm (F34→H36), and Er3+ emission around 1543 nm (I413/2→I415/2), was obtained under 792 nm laser excitation. The full width at half maximum of this integrated band increased with the increasing of [Tm]/[Er] ratio, and it reached as large as 175 nm for the 0.1 mol% Er3+ and 0.8 mol% Tm3+ co-doped sample. The energy transfers between Er3+ and Tm3+ were proposed to play an important role in tailoring the emission bandwidth of the sample.

  14. SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

    PubMed Central

    Villanova, Lidia; Brown, Katharine; Qiu, Xiaolei; Nabavi, Noushin; Mohrin, Mary; Wojnoonski, Kathleen; Li, Patrick; Cheng, Hwei-Ling; Murphy, Andrew J.; Valenzuela, David M.; Luo, Hanzhi; Kapahi, Pankaj; Krauss, Ronald; Mostoslavsky, Raul; Yancopoulos, George D.; Alt, Frederick W.; Chua, Katrin F.; Chen, Danica

    2014-01-01

    SUMMARY Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevents the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7 deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease. PMID:24210820

  15. Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy.

    PubMed

    Lépine, S; Allegood, J C; Park, M; Dent, P; Milstien, S; Spiegel, S

    2011-02-01

    The sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) have recently been implicated in autophagy. In this study, we report that depletion of sphingosine-1-phosphate phosphohydrolase-1 (SPP1), an endoplasmic reticulum (ER)-resident enzyme that specifically dephosphorylates S1P, induced autophagy. Although the mammalian target of rapamycin and class III phosphoinositide 3-kinase/Beclin-1 pathways were not involved and this autophagy was p53 independent, C/EBP homologous protein, BiP, and phospho-eucaryotic translation initiation factor-2α, and cleavage of procaspases 2 and 4, downstream targets of ER stress, were increased after SPP1 depletion. Autophagy was suppressed by depletion of protein kinase regulated by RNA-like ER kinase (PERK), inositol-requiring transmembrane kinase/endonuclease-1α, or activating transcription factor 6, three sensors of the unfolded protein response (UPR) to ER stress. Autophagy triggered by downregulation of SPP1 did not lead to apoptosis but rather stimulated, in a PERK dependent manner, the survival signal Akt, whose inhibition then sensitized cells to apoptosis. Although depletion of SPP1 increased intracellular levels of S1P and its secretion, activation of cell surface S1P receptors did not induce autophagy. Nevertheless, increases in intracellular pools of S1P, but not dihydro-S1P, induced autophagy and ER stress. Thus, SPP1, by regulating intracellular S1P homeostasis, can control the UPR and ER stress-induced autophagy. PMID:20798685

  16. A 4-DOF haptic master using ER fluid for minimally invasive surgery system application

    NASA Astrophysics Data System (ADS)

    Oh, Jong-Seok; Han, Young-Min; Lee, Sang-Rock; Choi, Seung-Bok

    2013-04-01

    This paper presents a novel 4-degrees-of-freedom (4-DOF) haptic master using a electrorheological (ER) fluid which is applicable to minimally invasive surgery (MIS) systems. By adopting a controllable ER fluid, the master can easily generate 4-DOF repulsive forces with the advantages of a simple mechanism and continuous force control capability. The proposed master consists of two actuators: an ER spherical joint for 3-DOF rotational motion and an ER piston device for 1-DOF translational motion. The generated torque/force models are mathematically derived by analyzing the mechanism geometry and using the Bingham characteristics of an ER Fluid. The haptic master is optimally designed and manufactured based on the mathematical torque/force models. The repulsive torque/force responses are experimentally evaluated and expressed by the first-order and second-order dynamic equations for each motion. A sliding mode controller (SMC), which is known to be robust to uncertainties, is then designed and empirically implemented to achieve the desired torque/force trajectories. It is demonstrated by presenting torque/force tracking results of both rotational and translational motions that the proposed 4-DOF ER haptic master integrated with the SMC can provide an effective haptic control performance for MIS applications.

  17. RTN1 mediates progression of kidney disease by inducing ER stress.

    PubMed

    Fan, Ying; Xiao, Wenzhen; Li, Zhengzhe; Li, Xuezhu; Chuang, Peter Y; Jim, Belinda; Zhang, Weijia; Wei, Chengguo; Wang, Niansong; Jia, Weiping; Xiong, Huabao; Lee, Kyung; He, John C

    2015-01-01

    Identification of new biomarkers and drug targets for chronic kidney disease (CKD) is required for the development of more effective therapy. Here we report an association between expression of reticulon 1 (RTN1) and severity of CKD. An isoform-specific increase in the expression of RTN1A is detected in the diseased kidneys from mice and humans, and correlates inversely with renal function in patients with diabetic nephropathy. RTN1 overexpression in renal cells induces ER stress and apoptosis, whereas RTN1 knockdown attenuates tunicamycin-induced and hyperglycaemia-induced ER stress and apoptosis. RTN1A interacts with PERK through its N-terminal and C-terminal domains, and mutation of these domains prevents this effect on ER stress. Knockdown of Rtn1a expression in vivo attenuates ER stress and renal fibrosis in mice with unilateral ureteral obstruction, and also attenuates ER stress, proteinuria, glomerular hypertrophy and mesangial expansion in diabetic mice. Together, these data indicate that RTN1A contributes to progression of kidney disease by inducing ER stress. PMID:26227493

  18. IMG ER: A System for Microbial Genome Annotation Expert Review and Curation

    SciTech Connect

    Markowitz, Victor M.; Mavromatis, Konstantinos; Ivanova, Natalia N.; Chen, I-Min A.; Chu, Ken; Kyrpides, Nikos C.

    2009-05-25

    A rapidly increasing number of microbial genomes are sequenced by organizations worldwide and are eventually included into various public genome data resources. The quality of the annotations depends largely on the original dataset providers, with erroneous or incomplete annotations often carried over into the public resources and difficult to correct. We have developed an Expert Review (ER) version of the Integrated Microbial Genomes (IMG) system, with the goal of supporting systematic and efficient revision of microbial genome annotations. IMG ER provides tools for the review and curation of annotations of both new and publicly available microbial genomes within IMG's rich integrated genome framework. New genome datasets are included into IMG ER prior to their public release either with their native annotations or with annotations generated by IMG ER's annotation pipeline. IMG ER tools allow addressing annotation problems detected with IMG's comparative analysis tools, such as genes missed by gene prediction pipelines or genes without an associated function. Over the past year, IMG ER was used for improving the annotations of about 150 microbial genomes.

  19. Rab18 and a Rab18 GEF complex are required for normal ER structure

    PubMed Central

    Gerondopoulos, Andreas; Bastos, Ricardo Nunes; Yoshimura, Shin-ichiro; Anderson, Rachel; Carpanini, Sarah; Aligianis, Irene

    2014-01-01

    The ancestral Rab GTPase Rab18 and both subunits of the Rab3GAP complex are mutated in the human neurological and developmental disorder Warburg Micro syndrome. Here, we demonstrate that the Rab3GAP complex is a specific Rab18 guanine nucleotide exchange factor (GEF). The Rab3GAP complex localizes to the endoplasmic reticulum (ER) and is necessary for ER targeting of Rab18. It is also sufficient to promote membrane recruitment of Rab18. Disease-associated point mutations of conserved residues in either the Rab3GAP1 (T18P and E24V) or Rab3GAP2 (R426C) subunits result in loss of the Rab18 GEF and membrane-targeting activities. Supporting the view that Rab18 activity is important for ER structure, in the absence of either Rab3GAP subunit or Rab18 function, ER tubular networks marked by reticulon 4 were disrupted, and ER sheets defined by CLIMP-63 spread out into the cell periphery. Micro syndrome is therefore a disease characterized by direct loss of Rab18 function or loss of Rab18 activation at the ER by its GEF Rab3GAP. PMID:24891604

  20. PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress

    PubMed Central

    Wang, Lifen; Ryoo, Hyung Don; Qi, Yanyan; Jasper, Heinrich

    2015-01-01

    Intestinal homeostasis requires precise control of intestinal stem cell (ISC) proliferation. In Drosophila, this control declines with age largely due to chronic activation of stress signaling and associated chronic inflammatory conditions. An important contributor to this condition is the age-associated increase in endoplasmic reticulum (ER) stress. Here we show that the PKR-like ER kinase (PERK) integrates both cell-autonomous and non-autonomous ER stress stimuli to induce ISC proliferation. In addition to responding to cell-intrinsic ER stress, PERK is also specifically activated in ISCs by JAK/Stat signaling in response to ER stress in neighboring cells. The activation of PERK is required for homeostatic regeneration, as well as for acute regenerative responses, yet the chronic engagement of this response becomes deleterious in aging flies. Accordingly, knocking down PERK in ISCs is sufficient to promote intestinal homeostasis and extend lifespan. Our studies highlight the significance of the PERK branch of the unfolded protein response of the ER (UPRER) in intestinal homeostasis and provide a viable strategy to improve organismal health- and lifespan. PMID:25945494