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Sample records for pga pumpesvigt er

  1. Pga1 Is an Essential Component of Glycosylphosphatidylinositol-Mannosyltransferase II of Saccharomyces cerevisiae

    PubMed Central

    Sato, Keisuke; Noda, Yoichi

    2007-01-01

    The Saccharomyces cerevisiae essential gene YNL158w/PGA1 encodes an endoplasmic reticulum (ER)-localized membrane protein. We constructed temperature-sensitive alleles of PGA1 by error-prone polymerase chain reaction mutagenesis to explore its biological role. Pulse-chase experiments revealed that the pga1ts mutants accumulated the ER-form precursor of Gas1 protein at the restrictive temperature. Transport of invertase and carboxypeptidase Y were not affected. Triton X-114 phase separation and [3H]inositol labeling indicated that the glycosylphosphatidylinositol (GPI)-anchoring was defective in the pga1ts mutants, suggesting that Pga1 is involved in GPI synthesis or its transfer to target proteins. We found GPI18, which was recently reported to encode GPI-mannosyltransferase II (GPI-MT II), as a high-copy suppressor of the temperature sensitivity of pga1ts. Both Gpi18 and Pga1 were detected in the ER by immunofluorescence, and they were coprecipitated from the Triton X-100–solubilized membrane. The gpi18ts and pga1ts mutants accumulated the same GPI synthetic intermediate at the restrictive temperature. From these results, we concluded that Pga1 is an additional essential component of the yeast GPI-MT II. PMID:17615295

  2. gPGA: GPU Accelerated Population Genetics Analyses

    PubMed Central

    Zhou, Chunbao; Lang, Xianyu; Wang, Yangang; Zhu, Chaodong

    2015-01-01

    Background The isolation with migration (IM) model is important for studies in population genetics and phylogeography. IM program applies the IM model to genetic data drawn from a pair of closely related populations or species based on Markov chain Monte Carlo (MCMC) simulations of gene genealogies. But computational burden of IM program has placed limits on its application. Methodology With strong computational power, Graphics Processing Unit (GPU) has been widely used in many fields. In this article, we present an effective implementation of IM program on one GPU based on Compute Unified Device Architecture (CUDA), which we call gPGA. Conclusions Compared with IM program, gPGA can achieve up to 52.30X speedup on one GPU. The evaluation results demonstrate that it allows datasets to be analyzed effectively and rapidly for research on divergence population genetics. The software is freely available with source code at https://github.com/chunbaozhou/gPGA. PMID:26248314

  3. Prediction of spectral acceleration response ordinates based on PGA attenuation

    USGS Publications Warehouse

    Graizer, V.; Kalkan, E.

    2009-01-01

    Developed herein is a new peak ground acceleration (PGA)-based predictive model for 5% damped pseudospectral acceleration (SA) ordinates of free-field horizontal component of ground motion from shallow-crustal earthquakes. The predictive model of ground motion spectral shape (i.e., normalized spectrum) is generated as a continuous function of few parameters. The proposed model eliminates the classical exhausted matrix of estimator coefficients, and provides significant ease in its implementation. It is structured on the Next Generation Attenuation (NGA) database with a number of additions from recent Californian events including 2003 San Simeon and 2004 Parkfield earthquakes. A unique feature of the model is its new functional form explicitly integrating PGA as a scaling factor. The spectral shape model is parameterized within an approximation function using moment magnitude, closest distance to the fault (fault distance) and VS30 (average shear-wave velocity in the upper 30 m) as independent variables. Mean values of its estimator coefficients were computed by fitting an approximation function to spectral shape of each record using robust nonlinear optimization. Proposed spectral shape model is independent of the PGA attenuation, allowing utilization of various PGA attenuation relations to estimate the response spectrum of earthquake recordings.

  4. Orthopaedic applications for PLA-PGA biodegradable polymers.

    PubMed

    Athanasiou, K A; Agrawal, C M; Barber, F A; Burkhart, S S

    1998-10-01

    Biodegradable polymers, especially those belonging to the family of polylactic acid (PLA) and polyglycolic acid (PGA), play an increasingly important role in orthopaedics. These polymers degrade by hydrolysis and enzymatic activity and have a range of mechanical and physical properties that can be engineered appropriately to suit a particular application. Their degradation characteristics depend on several parameters including their molecular structure, crystallinity, and copolymer ratio. These biomaterials are also rapidly gaining recognition in the fledging field of tissue engineering because they can be fashioned into porous scaffolds or carriers of cells, extracellular matrix components, and bioactive agents. Although their future appears to be bright, several questions regarding the biocompatibility of these materials linger and should be addressed before their wide-scale use. In the context of musculoskeletal tissue, this report provides a comprehensive review of properties and applications of biodegradable PLA/PGA polymers and their copolymers. Of special interest are orthopaedic applications, biocompatibility studies, and issues of sterilization and storage of these versatile biomaterials. Also discussed is the fact that terms such as PLA, PGA, or PLA-PGA do not denote one material, but rather a large family of materials that have a wide range of differing bioengineering properties and concomitant biological responses. An analysis of some misconceptions, problems, and potential solutions is also provided. PMID:9788368

  5. Effect of γ-PGA on the formation of collagen fibrils in vitro.

    PubMed

    Ding, Cuicui; Zheng, Zhigong; Liu, Xinzhong; Li, Hengda; Zhang, Min

    2016-07-01

    The effect of γ-poly(glutamic acid) (γ-PGA) on the self-assembly of collagen was studied. Under physiological conditions, the kinetic curves for fibril formation showed that the turbidity of collagen/γ-PGA blends at 313 nm was increased with the addition of γ-PGA. Furthermore, it was shown using both field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) that fibrils with a larger diameter were obtained following the addition of γ-PGA, probably due to the electrostatic and hydrogen bond interactions between collagen and γ-PGA, which promoted the lateral association of collagen molecules. In addition, both the thermal stability and viscoelastic properties of the hybrid hydrogels, which were evaluated by differential scanning calorimetry and rheological measurements, respectively, were improved by the addition of γ-PGA. PMID:26940941

  6. iPGA: incremental principal geodesic analysis with applications to movement disorder classification.

    PubMed

    Salehian, Hesamoddin; Vaillancourt, David; Vemuri, Baba C

    2014-01-01

    The nonlinear version of the well known PCA called the Prinicipal Geodesic Analysis (PGA) was introduced in the past decade for statistical analysis of shapes as well as diffusion tensors. PGA of diffusion tensor fields or any other manifold-valued fields can be a computationally demanding task due to the dimensionality of the problem and thus establishing motivation for an incremental PGA (iPGA) algorithm. In this paper, we present a novel iPGA algorithm that incrementally updates the current Karcher mean and the principal sub-manifolds with any newly introduced data into the pool without having to recompute the PGA from scratch. We demonstrate substantial computational and memory savings of iPGA over the batch mode PGA for diffusion tensor fields via synthetic and real data examples. Further, we use the iPGA derived representation in an NN classifier to automatically discriminate between controls, Parkinson's Disease and Essential Tremor patients, given their HARDI brain scans. PMID:25485449

  7. Determinants of Club Head Speed in PGA Professional Golfers.

    PubMed

    Lewis, Adam L; Ward, Nick; Bishop, Chris; Maloney, Sean; Turner, Anthony N

    2016-08-01

    Turner, AN. Determinants of club head speed in PGA professional golfers. J Strength Cond Res 30(8): 2266-2270, 2016-Club head speed (CHS) has been significantly correlated with golf performance, but only in amateurs. The purpose of this study therefore, was to investigate the relationship between field-based measures of strength and power with CHS in Professional Golfers Association (PGA) professional golfers, and further determine differences between age groups. A correlation design was used to test relationships between squat jump (SJ), seated medicine ball throw (SMBT), rotational medicine ball throw (RMBT), and CHS. Twenty participants volunteered to take part in the study (age, 31.95 ± 8.7 years; height, 182.75 ± 6.88 cm; mass, 90.47 ± 15.6 kg). Intraclass correlation coefficients reported high reliability for performance variables (r = 0.85-0.95). Significant correlations (p < 0.01) were found between CHS and SJ (r = 0.817) and SMBT (r = 0.706), but not RMBT (r = 0.572). A stepwise linear regression analysis identified that SJ and SMBT explained 74% of the variance in CHS. When dividing the sample based on age, professionals <30 years (n = 10; 25.6 ± 2.9 years) displayed significantly (p ≤ 0.05) higher CHS and SJ height compared with professionals >30 (n = 10; 39.7 ± 5.5 years). Correlations to CHS for <30 were significant for SJ (r = 0.801) and SMBT (r = 0.643), but nonsignificant for RMBT. Those >30 had significant correlations to CHS not only in SMBT (r = 0.881) and SJ (r = 0.729), but also in RMBT (r = 0.642). The results of this study suggest that SJ and SMBT have the largest contribution to CHS in PGA professional golfers. When comparing age groups, it appears that younger golfers (<30 years) utilize more leg strength whereas older golfers (>30 years) utilize more upper body strength. Results suggest that strength-based leg exercises and power-based chest exercises may improve CHS in professional golfers. PMID:26849785

  8. γ-PGA Hydrolases of Phage Origin in Bacillus subtilis and Other Microbial Genomes.

    PubMed

    Mamberti, Stefania; Prati, Paola; Cremaschi, Paolo; Seppi, Claudio; Morelli, Carlo F; Galizzi, Alessandro; Fabbi, Massimo; Calvio, Cinzia

    2015-01-01

    Poly-γ-glutamate (γ-PGA) is an industrially interesting polymer secreted mainly by members of the class Bacilli which forms a shield able to protect bacteria from phagocytosis and phages. Few enzymes are known to degrade γ-PGA; among them is a phage-encoded γ-PGA hydrolase, PghP. The supposed role of PghP in phages is to ensure access to the surface of bacterial cells by dismantling the γ-PGA barrier. We identified four unannotated B. subtilis genes through similarity of their encoded products to PghP; in fact these genes reside in prophage elements of B. subtilis genome. The recombinant products of two of them demonstrate efficient polymer degradation, confirming that sequence similarity reflects functional homology. Genes encoding similar γ-PGA hydrolases were identified in phages specific for the order Bacillales and in numerous microbial genomes, not only belonging to that order. The distribution of the γ-PGA biosynthesis operon was also investigated with a bioinformatics approach; it was found that the list of organisms endowed with γ-PGA biosynthetic functions is larger than expected and includes several pathogenic species. Moreover in non-Bacillales bacteria the predicted γ-PGA hydrolase genes are preferentially found in species that do not have the genetic asset for polymer production. Our findings suggest that γ-PGA hydrolase genes might have spread across microbial genomes via horizontal exchanges rather than via phage infection. We hypothesize that, in natural habitats rich in γ-PGA supplied by producer organisms, the availability of hydrolases that release glutamate oligomers from γ-PGA might be a beneficial trait under positive selection. PMID:26158264

  9. γ-PGA Hydrolases of Phage Origin in Bacillus subtilis and Other Microbial Genomes

    PubMed Central

    Mamberti, Stefania; Prati, Paola; Cremaschi, Paolo; Seppi, Claudio; Morelli, Carlo F.; Galizzi, Alessandro; Fabbi, Massimo; Calvio, Cinzia

    2015-01-01

    Poly-γ-glutamate (γ-PGA) is an industrially interesting polymer secreted mainly by members of the class Bacilli which forms a shield able to protect bacteria from phagocytosis and phages. Few enzymes are known to degrade γ-PGA; among them is a phage-encoded γ-PGA hydrolase, PghP. The supposed role of PghP in phages is to ensure access to the surface of bacterial cells by dismantling the γ-PGA barrier. We identified four unannotated B. subtilis genes through similarity of their encoded products to PghP; in fact these genes reside in prophage elements of B. subtilis genome. The recombinant products of two of them demonstrate efficient polymer degradation, confirming that sequence similarity reflects functional homology. Genes encoding similar γ-PGA hydrolases were identified in phages specific for the order Bacillales and in numerous microbial genomes, not only belonging to that order. The distribution of the γ-PGA biosynthesis operon was also investigated with a bioinformatics approach; it was found that the list of organisms endowed with γ-PGA biosynthetic functions is larger than expected and includes several pathogenic species. Moreover in non-Bacillales bacteria the predicted γ-PGA hydrolase genes are preferentially found in species that do not have the genetic asset for polymer production. Our findings suggest that γ-PGA hydrolase genes might have spread across microbial genomes via horizontal exchanges rather than via phage infection. We hypothesize that, in natural habitats rich in γ-PGA supplied by producer organisms, the availability of hydrolases that release glutamate oligomers from γ-PGA might be a beneficial trait under positive selection. PMID:26158264

  10. PGA-incorporated collagen: Toward a biodegradable composite scaffold for bone-tissue engineering.

    PubMed

    Toosi, Shirin; Naderi-Meshkin, Hojjat; Kalalinia, Fatemeh; Peivandi, Mohammad Taghi; HosseinKhani, Hossein; Bahrami, Ahmad Reza; Heirani-Tabasi, Asieh; Mirahmadi, Mahdi; Behravan, Javad

    2016-08-01

    Nowadays composite scaffolds based on synthetic and natural biomaterials have got attention to increase healing of non-union bone fractures. To this end, different aspects of collagen sponge incorporated with poly(glycolic acid) (PGA) fiber were investigated in this study. Collagen solution (6.33 mg/mL) with PGA fibers (collagen/fiber ratio [w/w]: 4.22, 2.11, 1.06, 0.52) was freeze-dried, followed by dehydrothermal cross-linking to obtain collagen sponge incorporating PGA fibers. Properties of scaffold for cell viability, proliferation, and differentiation of mesenchymal stem cells (MSCs) were evaluated. Scanning electron microscopy showed that collagen sponge exhibited an interconnected pore structure with an average pore size of 190 μm, irrespective of PGA fiber incorporation. The collagen-PGA sponge was superior to the original collagen sponge in terms of the initial attachment, proliferation rate, and osteogenic differentiation of the bone marrow-MSCs (BM-MSC). The shrinkage of sponges during cell culture was significantly suppressed by fiber incorporation. Incorporation of PGA fiber is a simple and promising way to reinforce collagen sponge without impairing biocompatibility. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2020-2028, 2016. PMID:27059133

  11. Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis.

    PubMed

    Teare, J P; Sherman, D; Greenfield, S M; Simpson, J; Bray, G; Catterall, A P; Murray-Lyon, I M; Peters, T J; Williams, R; Thompson, R P

    1993-10-01

    In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs

  12. Poly-γ-Glutamic Acid (PGA)-Producing Bacillus Species Isolated from Kinema, Indian Fermented Soybean Food

    PubMed Central

    Chettri, Rajen; Bhutia, Meera O.; Tamang, Jyoti P.

    2016-01-01

    Kinema, an ethnic fermented, non-salted and sticky soybean food is consumed in the eastern part of India. The stickiness is one of the best qualities of good kinema preferred by consumers, which is due to the production of poly-γ-glutamic acid (PGA). Average load of Bacillus in kinema was 107 cfu/g and of lactic acid bacteria was 103 cfu/g. Bacillus spp. were screened for PGA-production and isolates of lactic acid bacteria were also tested for degradation of PGA. Only Bacillus produced PGA, none of lactic acid bacteria produced PGA. PGA-producing Bacillus spp. were identified by phenotypic characterization and also by 16S rRNA gene sequencing as Bacillus subtilis, B. licheniformis and B. sonorensis. PMID:27446012

  13. Production of Poly-γ-Glutamate (PGA) Biopolymer by Batch and Semicontinuous Cultures of Immobilized Bacilluslicheniformis strain-R

    PubMed Central

    Berekaa, Mahmoud M.; El Aassar, Samy A.; El-Sayed, Samia M.; EL Borai, Aliaa M.

    2009-01-01

    Production of Polyglutamate (PGA) biopolymer by immobilized Bacillus licheniformis strain-R was intensively investigated. Preliminary experiments were carried out to address the most suitable immobilization methodology. Entrapment of Bacillus cells in alginate–agar led optimal PGA production (36.75 g/l), with 1.32-and 2.18-fold increase in comparison with alginate-or K-carrageenan-immobilized cells, respectively. During semicontinuous cultivation of agar-alginate gel-cell mixture, production of PGA by 10 ml mixture was increased from 2nd to 3rd run whereas, increased till the 4th run using 15ml mixture. Adsorption was the most suitable immobilization technique for production of PGA and the sponge cubes was the preferred matrix recording 43.2 g/l of PGA with the highest cell adsorption. Furthermore, no PGA was detected when B. licheniformis cells were adsorbed on wood and pumice. Although luffa pulp-adsorbed cells recorded the highest PGA production (50.4 g/l), cell adsorption was the lowest. Semicontinuous cultivation of B. licheniformis cells adsorbed on sponge led to increase of PGA production till the 3rd run and reached 55.5 g/l then slightly decreased in the 4th run. The successful use of fixed-bed bioreactor for semicontinuous cultivation of B. licheniformis cells held on sponge cubes (3 runs, 96 hours/run) provides insight for the potential biotechnological production of PGA by immobilized cells. PMID:24031418

  14. Evaluation of PEG and mPEG-co-(PGA-co-PDL) microparticles loaded with sodium diclofenac

    PubMed Central

    Tawfeek, Hesham M.

    2013-01-01

    The aim of this study was to synthesize and evaluate novel biodegradable polyesters namely; poly(ethylene glycol)-Poly(glycerol adipate-co-ω-pentadecalactone), PEG-PGA-co-PDL-PEG, and poly(ethylene glycol methyl ether)-Poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL-PEGme as an alternative sustained release carrier for lung delivery compared with non-PEG containing polymer PGA-co-PDL. The co-polymers were synthesized through lipase catalysis ring opening polymerization reaction and characterized using GPC, FT-IR, 1H-NMR and surface contact angle. Furthermore, microparticles containing a model hydrophilic drug, sodium diclofenac, were prepared via spray drying from a modified single emulsion and characterized for their encapsulation efficiency, geometrical particle size, zeta potential, tapped density, primary aerodynamic diameter, amorphous nature, morphology, in vitro release and the aerosolization performance. Microparticles fabricated from mPEG-co-polymer can be targeted to the lung periphery with an optimum in vitro deposition. Furthermore, a significantly higher in vitro release (p > 0.05, ANOVA/Dunnett’s) was observed with the PEG and mPEG-co-polymers compared to PGA-co-PDL. In addition, these co-polymers have a good safety profile upon testing on human bronchial epithelial, 16HBE14o- cell lines. PMID:24227959

  15. Effect of topical prostaglandin PGA2, PGA2 isopropyl ester, and PGF2 alpha isopropyl ester on intraocular pressure in normotensive and glaucomatous canine eyes.

    PubMed

    Gum, G G; Kingsbury, S; Whitley, R D; Garcia, A; Gelatt, K N

    1991-01-01

    Topical instillations of 1.0, 10, and 20 micrograms/50 microliters of prostaglandin PGA2, 0.5 and 1.0 microgram/50 microliters of PGA2 isopropyl ester, and 0.5, 1.0, 5.0 and 10.0 micrograms/50 microliters of PGF2 alpha isopropyl ester were evaluated in the normal dogs and glaucomatous beagles eyes. Each concentration of drug was evaluated for a seven day period. On Day 1 baseline values were obtained, days 2-4, the drug was instilled (once a day) and on days 5-7 post-treatment values were measured. All concentrations of PGA2 failed to lower intraocular pressure (IOP) in the normal and the glaucomatous (P greater than 0.72) dogs. PGA2 isopropyl ester decreased IOP in the normal dogs and in the glaucomatous beagles (P less than 0.01). The declines in IOP were significant at 1/2 to 1 hour and continued for up to 5 hours. No significant change in IOP occurred in the non-treated fellow eye of the normotensive dog (P less than 0.54) and the glaucomatous beagle (P less than 0.29). All concentrations of PGF2 alpha isopropyl ester significantly decreased IOP in the treated eyes of the normotensive dog (P less than 0.05) and the glaucomatous beagle (P less than 0.01). The significant change in IOP occurred within one hour after the instillation of PGF2 alpha isopropyl ester. The IOP remained lower than the baseline pressures 24 hours post-treatment for both the normotensive and glaucomatous dogs. Maximal change in IOP for normal dogs was a decrease of 9 mm Hg while the glaucomatous beagle had a decrease of 19 mm Hg. No significant change in IOP occurred in the non-treated fellow eye of the normotensive animal (P less than 0.16) and the glaucomatous beagle (P less than 0.40). The side effects of PGF2 alpha isopropyl ester were miosis and mild conjunctival irritation. PMID:1919268

  16. Properties of starch-polyglutamic acid (PGA) graft copolymer prepared by microwave irradiation - the Fourier transform infrared spectroscopy (FTIR) and rheology studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rheological properties of waxy starch-'-polygutamic acid (PGA) graft copolymers were investigated. The starch-PGA copolymers absorbed water and formed gels, which exhibited concentration-dependent viscoelastic solid properties. Higher starch-PGA concentrations resulted in stronger viscoelastic p...

  17. Influence of weak motion data to magnitude dependence of PGA prediction model in Austria

    NASA Astrophysics Data System (ADS)

    Jia, Yan

    2015-04-01

    Data recorded by the STS2-sensors at the Austrian Seismic Network were differentiated and used to derive the PGA prediction model for Austria (Jia and Lenhardt, 2010). Before using it to our hazard assessment and real time shakemap, it is necessary to validate this model and obtain a deep understanding about it. In this paper, influence of weak motion data to the magnitude dependence of our prediction model was studied. In addition, spatial PGA residuals between the measurements and predictions were investigated as well. There are 127 earthquakes with a magnitude between 3 and 5.4 that were used to derive the PGA prediction model published in 2011. Unfortunately, 90% of used PGA measurements were made for the events with a magnitude smaller than 4. Only ten quakes among them have a magnitude larger than 4, which is the important magnitude range that needs our attention and hazard assessment. In this investigation, 127 earthquakes were divided into two groups: the first group only includes events with a magnitude smaller than 4, while the second group contains quakes with a magnitude larger than 4. By using the same modeling for estimating PGA attenuation in 2011, coefficients of the model were inverted from the measurements in two groups and compared to the one based on the complete data set. It was found that the group with the weak quakes returned results that only have small differences to the one from all 127 events, while the group with strong quakes (ml> 4) gave greater magnitude dependence than the model published in 2011. The distance coefficients stayed nearly unchanged for all three inversions. As the second step, spatial PGA residuals between the measurements and the predictions from our model were investigated. As explained in Jia and Lenhardt (2013), there are some differences in the site amplifications between the West- and the East-Austria. For a fair comparison, residuals were normalized for each station before the investigation. Then normalized

  18. The pgaABCD Locus of Escherichia coli Promotes the Synthesis of a Polysaccharide Adhesin Required for Biofilm Formation

    PubMed Central

    Wang, Xin; Preston, James F.; Romeo, Tony

    2004-01-01

    Production of a polysaccharide matrix is a hallmark of bacterial biofilms, but the composition of matrix polysaccharides and their functions are not widely understood. Previous studies of the regulation of Escherichia coli biofilm formation suggested the involvement of an unknown adhesin. We now establish that the pgaABCD (formerly ycdSRQP) locus affects biofilm development by promoting abiotic surface binding and intercellular adhesion. All of the pga genes are required for optimal biofilm formation under a variety of growth conditions. A pga-dependent cell-bound polysaccharide was isolated and determined by nuclear magnetic resonance analyses to consist of unbranched β-1,6-N-acetyl-d-glucosamine, a polymer previously unknown from the gram-negative bacteria but involved in adhesion by staphylococci. The pga genes are predicted to encode envelope proteins involved in synthesis, translocation, and possibly surface docking of this polysaccharide. As predicted, if poly-β-1,6-GlcNAc (PGA) mediates cohesion, metaperiodate caused biofilm dispersal and the release of intact cells, whereas treatment with protease or other lytic enzymes had no effect. The pgaABCD operon exhibits features of a horizontally transferred locus and is present in a variety of eubacteria. Therefore, we propose that PGA serves as an adhesin that stabilizes biofilms of E. coli and other bacteria. PMID:15090514

  19. Transcriptome Profiling of Wild-Type and pga-Knockout Mutant Strains Reveal the Role of Exopolysaccharide in Aggregatibacter actinomycetemcomitans

    PubMed Central

    Shanmugam, Mayilvahanan; El Abbar, Faiha; Ramasubbu, Narayanan

    2015-01-01

    Exopolysaccharides have a diverse set of functions in most bacteria including a mechanistic role in protecting bacteria against environmental stresses. Among the many functions attributed to the exopolysaccharides, biofilm formation, antibiotic resistance, immune evasion and colonization have been studied most extensively. The exopolysaccharide produced by many Gram positive as well as Gram negative bacteria including the oral pathogen Aggregatibacter actinomycetemcomitans is the homopolymer of β(1,6)-linked N-acetylglucosamine. Recently, we reported that the PGA-deficient mutant of A. actinomycetemcomitans failed to colonize or induce bone resorption in a rat model of periodontal disease, and the colonization genes, apiA and aae, were significantly down regulated in the mutant strain. To understand the role of exopolysaccharide and the pga locus in the global expression of A. actinomycetemcomitans, we have used comparative transcriptome profiling to identify differentially expressed genes in the wild-type strain in relation to the PGA-deficient strain. Transcriptome analysis revealed that about 50% of the genes are differently expressed (P < 0.05 and fold change >1.5). Our study demonstrated that the absence of the pga locus affects the genes involved in peptidoglycan recycling, glycogen storage, and virulence. Further, using confocal microscopy and plating assays, we show that the viability of pga mutant strain is significantly reduced during biofilm growth. Thus, this study highlights the importance of pga genes and the exopolysaccharide in the virulence of A. actinomycetemcomitans. PMID:26221956

  20. Seismic Intensity, PGA and PGV for the South Napa Earthquake, August 24, 2014

    NASA Astrophysics Data System (ADS)

    Chen, S.; Pickering, A.; Mooney, W. D.; Crewdson, E.

    2014-12-01

    Numerous studies have investigated the statistical relationship between Modified Mercalli Intensity (MMI) and peak ground acceleration (PGA) and peak ground velocity (PGV). The Mw 6.0 South Napa (California) earthquake of August 24, 2014 provides valuable data to examine these relationships for both urban and rural environments within northern California. The finite fault model (D. Dreger, 2014) indicates that the fault rupture propagated predominantly NNW and up-dip from a 11-km-deep hypocenter. The epicentral location was 8 km SSW of downtown Napa. Recorded PGA north of the epicenter is as high as 600 cm/s2 and PGV locally reaches 80 cm/s. Field studies by two teams of investigators were conducted on August 24-26 and September 8-11, 2014 to assign MMI values at 108 sites. The highest MMI values are strongly localized along the NNW-SSE rupture trend north of the epicenter. Parts of the city of Napa and some communities several km farther north on Dry Creek Road were found to have experienced shaking intensities of MMI VII to VIII. The observed effects include houses moved off their foundations, chimney collapse or damage, cracked foundations and/or interior walls, broken windows, and the lateral displacement of heavy furniture. Communities to the east and west of this zone of high seismic intensity reported significantly lower values of MMI, typically IV and V even at distances as close as 10 km from the mapped surface rupture. In comparison with previous estimates by Wald et al. (1999) and Dangkua and Cramer (2011), we find that MMI III-VIII uniformly correspond to significantly larger (>150%) PGA and PGV values, as reported by the Center for Engineering Strong Motion Data (2014). We attribute this observation to two primary factors: (1) improved earthquake engineering in the post-Loma Prieta earthquake era that has led to building construction, both new and retrofitted, that is more resistant to earthquake strong ground motions; and (2) a frequency band relevant

  1. rPbPga1 from Paracoccidioides brasiliensis Activates Mast Cells and Macrophages via NFkB

    PubMed Central

    Valim, Clarissa Xavier Resende; da Silva, Elaine Zayas Marcelino; Assis, Mariana Aprigio; Fernandes, Fabricio Freitas; Coelho, Paulo Sergio Rodrigues; Oliver, Constance; Jamur, Maria Célia

    2015-01-01

    Background The fungus Paracoccidioides brasiliensis is the leading etiological agent of paracoccidioidomycosis (PCM), a systemic granulomatous disease that typically affects the lungs. Cell wall components of P. brasiliensis interact with host cells and influence the pathogenesis of PCM. In yeast, many glycosylphosphatidylinositol (GPI)-anchored proteins are important in the initial contact with the host, mediating host-yeast interactions that culminate with the disease. PbPga1 is a GPI anchored protein located on the surface of the yeast P. brasiliensis that is recognized by sera from PCM patients. Methodology/Principal Findings Endogenous PbPga1 was localized to the surface of P. brasiliensis yeast cells in the lungs of infected mice using a polyclonal anti-rPbPga1 antibody. Furthermore, macrophages stained with anti-CD38 were associated with P. brasiliensis containing granulomas. Additionally, rPbPga1 activated the transcription factor NFkB in the macrophage cell line Raw 264.7 Luc cells, containing the luciferase gene downstream of the NFkB promoter. After 24 h of incubation with rPbPga1, alveolar macrophages from BALB/c mice were stimulated to release TNF-α, IL-4 and NO. Mast cells, identified by toluidine blue staining, were also associated with P. brasiliensis containing granulomas. Co-culture of P. Brasiliensis yeast cells with RBL-2H3 mast cells induced morphological changes on the surface of the mast cells. Furthermore, RBL-2H3 mast cells were degranulated by P. brasiliensis yeast cells, but not by rPbPga1, as determined by the release of beta-hexosaminidase. However, RBL-2H3 cells activated by rPbPga1 released the inflammatory interleukin IL-6 and also activated the transcription factor NFkB in GFP-reporter mast cells. The transcription factor NFAT was not activated when the mast cells were incubated with rPbPga1. Conclusions/Significance The results indicate that PbPga1 may act as a modulator protein in PCM pathogenesis and serve as a useful target for

  2. PGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes.

    PubMed

    Anta, B; Pérez-Rodríguez, A; Castro, J; García-Domínguez, C A; Ibiza, S; Martínez, N; Durá, L M; Hernández, S; Gragera, T; Peña-Jiménez, D; Yunta, M; Zarich, N; Crespo, P; Serrador, J M; Santos, E; Muñoz, A; Oliva, J L; Rojas-Cabañeros, J M

    2016-01-01

    The cyclopentenone prostaglandin A1 (PGA1) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA1 triggers apoptosis by a process that entails the specific activation of H- and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA1 treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118S, defective for binding PGA1, did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA1 evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment. PMID:27468687

  3. PGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes

    PubMed Central

    Anta, B; Pérez-Rodríguez, A; Castro, J; García- Domínguez, C A; Ibiza, S; Martínez, N; Durá, L M; Hernández, S; Gragera, T; Peña-Jiménez, D; Yunta, M; Zarich, N; Crespo, P; Serrador, J M; Santos, E; Muñoz, A; Oliva, J L; Rojas-Cabañeros, J M

    2016-01-01

    The cyclopentenone prostaglandin A1 (PGA1) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA1 triggers apoptosis by a process that entails the specific activation of H- and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA1 treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118S, defective for binding PGA1, did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA1 evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment. PMID:27468687

  4. Estimation of Peak Ground Acceleration (PGA) for Peninsular Malaysia using geospatial approach

    NASA Astrophysics Data System (ADS)

    Nouri Manafizad, Amir; Pradhan, Biswajeet; Abdullahi, Saleh

    2016-06-01

    Among the various types of natural disasters, earthquake is considered as one of the most destructive events which impose a great amount of human fatalities and economic losses. Visualization of earthquake events and estimation of peak ground motions provides a strong tool for scientists and authorities to predict and mitigate the aftereffects of earthquakes. In addition it is useful for some businesses like insurance companies to evaluate the amount of investing risk. Although Peninsular Malaysian is situated in the stable part of Sunda plate, it is seismically influenced by very active earthquake sources of Sumatra's fault and subduction zones. This study modelled the seismic zones and estimates maximum credible earthquake (MCE) based on classified data for period 1900 to 2014. The deterministic approach was implemented for the analysis. Attenuation equations were used for two zones. Results show that, the PGA produced from subduction zone is from 2-64 (gal) and from the fault zone varies from 1-191(gal). In addition, the PGA generated from fault zone is more critical than subduction zone for selected seismic model.

  5. Immobilization and Characterization of Penicillin G Acylase (PGA) Immobilized on Magnetic Ni₀.₅Zn₀.₅Fe₂O₄ Nanoparticles.

    PubMed

    Liu, Ruijiang; Fan, Jiawen; Zhang, Yewang; Wang, Peng; Shen, Xiangqian

    2016-01-01

    Magnetic Ni₀.₅Zn₀.₅Fe₂O₄ nanoparticles were prepared via the solution combustion process and their microstructure and magnetic properties were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The as-prepared magnetic Ni₀.₅Zn₀.₅Fe₂O₄ nanoparticles are characterized with average grain size of about 20 nm and magnetization of 90.3 Am²/kg. The surface of magnetic Ni₀.₅Zn₀.₅Fe₂O₄ nanoparticles was modified by use of sodium silicate and N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, and the penicillin G acylase (PGA) was successfully immobilized on the surface-modified magnetic Ni₀.₅Zn₀.₅Fe₂O₄ nanoparticles. The results show that the activity for the immobilized PGA is affected less by pH and temperature than that for the free PGA, and the immobilized PGA exhibits a high effective activity, good stability of enzyme catalyst. This immobilized PGA on magnetic Ni₀.₅Zn₀.₅Fe₂O₄ nanoparticles can be separated from the solution by the external magnetic field for cyclic utilization, and they could retain about 70% of initial enzyme activity after 11 consecutive operations. The kinetic parameters (Km and Vmax) were determined, and the value of Km for the immobilized PGA (204.53 mmol/L) is higher than that of the free enzyme (3.50 mmol/L), while Vmax (1.93 mmol/min) is also larger than that of the free enzyme (0.838 mmol/min). PMID:27398443

  6. Observation to empirical PGA ratio estimates the relative thickness of sediment

    NASA Astrophysics Data System (ADS)

    Muzli, M.; Abidin, Z.; Sunarjo

    2016-05-01

    The amplification of earthquake seismic waves near the surface can vary significantly spatially due to differences in the thickness of sediments above the bedrock. Normally, the determination of sediment thickness is done by comparing the amplitude of the earthquake waveform recorded on the surface with the waveforms recorded on the sensors located on bedrock or borehole. This method, however, is still difficult to use, especially in Indonesia due to the small number of borehole sensors. As an alternative we propose a method to estimate the relative thickness of sediment in a region. It can be done by calculating the PGA ratio between the waveform recorded on the surface with the one calculated using an empirical formula. We then validate these results using the Horizontal to Vertical Spectral Ratio (HVSR) method.

  7. Prediction of the variation of PGA strength during hydrolysis by a combination of empirical equation, density functional theory calculation, and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Chen, Chuan; Ju, Shin-Pon; Huang, Wei-Chun; Lin, Jenn-Sen; Chen, Chien-Chia

    2014-07-01

    The strength variation of polyglycolic acid (PGA) during the hydrolysis process was predicted by the Flory-Fox model with all required parameters obtained by the theoretical approach. The density functional theory (DFT) calculation with the simple transition theory was used to derive the degradation rate constants of PGA intermediate at different temperatures and external load. The ultimate strength of PGA with infinite chain length, can be obtained by linearly extrapolating the ultimate strengths of three PGA materials with shorter chains. Although this Flory-Fox model formula combined with DFT calculation and MD simulation can only provide a qualitative comparison to those by experimental approaches, the current theoretical approach can provide an economical and quick way to assess the variation of PGA ultimate strength during hydrolysis.

  8. A Synthetic Bandwidth Method for High-Resolution SAR Based on PGA in the Range Dimension

    PubMed Central

    Li, Jincheng; Chen, Jie; Liu, Wei; Wang, Pengbo; Li, Chunsheng

    2015-01-01

    The synthetic bandwidth technique is an effective method to achieve ultra-high range resolution in an SAR system. There are mainly two challenges in its implementation. The first one is the estimation and compensation of system errors, such as the timing deviation and the amplitude-phase error. Due to precision limitation of the radar instrument, construction of the sub-band signals becomes much more complicated with these errors. The second challenge lies in the combination method, that is how to fit the sub-band signals together into a much wider bandwidth. In this paper, a novel synthetic bandwidth approach is presented. It considers two main errors of the multi-sub-band SAR system and compensates them by a two-order PGA (phase gradient auto-focus)-based method, named TRPGA. Furthermore, an improved cut-paste method is proposed to combine the signals in the frequency domain. It exploits the redundancy of errors and requires only a limited amount of data in the azimuth direction for error estimation. Moreover, the up-sampling operation can be avoided in the combination process. Imaging results based on both simulated and real data are presented to validate the proposed approach. PMID:26131679

  9. End-Group Effects on the Properties of PEG-co-PGA Hydrogels

    PubMed Central

    Bencherif, Sidi A.; Srinivasan, Abiraman; Sheehan, Jeffrey A.; Walker, Lynn M.; Gayathri, Chakicherla; Gil, Roberto; Hollinger, Jeffrey O.; Matyjaszewski, Krzysztof; Washburn, Newell R.

    2009-01-01

    A series of resorbable poly(ethylene glycol)-co-poly(glycolic acid) macromonomers have been synthesized with the chemistries from three different photopolymerizable end-groups (acrylates, methacrylates, and urethane methacrylates). The aim of the study is to examine the effects of the chemistry of the cross-linker group on the properties of photocross-linkable hydrogels. PEG-co-PGA (4KG5) hydrogels were prepared by photopolymerization with high vinyl group conversion as confirmed by 1H NMR spectroscopy using DOSY 1D pulse sequence. Our study reveals that the nature of end-groups in a moderately amphiphilic polymer can adjust the distribution and size of the micellar configuration in water leading to changes in the macroscopic structure of hydrogels. By varying the chemistry of the cross-linker group (diacrylates; DA, dimethacrylates; DM, and urethane dimethacrylates; UDM), we determined that the hydrophobocity of a single core polymer consisting of poly(glycolic acid) could be fine-tuned leading to significant variations in the mechanical, swelling, and degradation properties of the gels. In addition, the effects of cross-linker chemistry on cytotoxicity and proliferation were examined. Cytotoxicity assays showed that all the three types of hydrogels (4KG5 DA, DM, and UDM) were biocompatible and the introduction of RGD ligand enhanced cell adhesion. However, differences in gel properties and stability differentially affected the spreading and proliferation of myoblast C2C12 cells. PMID:19328754

  10. Strong motion PGA prediction for southwestern China from small earthquake records

    NASA Astrophysics Data System (ADS)

    Tao, Zhengru; Tao, Xiaxin; Cui, Anping

    2016-05-01

    For regions without enough strong ground motion records, a seismology-based method is adopted to predict motion PGA (peak ground acceleration) values on rock sites with parameters from small earthquake data, recorded by regional broadband digital monitoring networks. Sichuan and Yunnan regions in southwestern China are selected for this case study. Five regional parameters of source spectrum and attenuation are acquired from a joint inversion by the micro-genetic algorithm. PGAs are predicted for earthquakes with moment magnitude (Mw) 5.0, 6.0, and 7.0 respectively and a series of distances. The result is compared with limited regional strong motion data in the corresponding interval Mw ± 0.5. Most of the results ideally pass through the data clusters, except the case of Mw7.0 in the Sichuan region, which shows an obvious slow attenuation due to a lack of observed data from larger earthquakes (Mw ≥ 7.0). For further application, the parameters are adopted in strong motion synthesis at two near-fault stations during the great Wenchuan Earthquake M8.0 in 2008.

  11. A Synthetic Bandwidth Method for High-Resolution SAR Based on PGA in the Range Dimension.

    PubMed

    Li, Jincheng; Chen, Jie; Liu, Wei; Wang, Pengbo; Li, Chunsheng

    2015-01-01

    The synthetic bandwidth technique is an effective method to achieve ultra-high range resolution in an SAR system. There are mainly two challenges in its implementation. The first one is the estimation and compensation of system errors, such as the timing deviation and the amplitude-phase error. Due to precision limitation of the radar instrument, construction of the sub-band signals becomes much more complicated with these errors. The second challenge lies in the combination method, that is how to fit the sub-band signals together into a much wider bandwidth. In this paper, a novel synthetic bandwidth approach is presented. It considers two main errors of the multi-sub-band SAR system and compensates them by a two-order PGA (phase gradient auto-focus)-based method, named TRPGA. Furthermore, an improved cut-paste method is proposed to combine the signals in the frequency domain. It exploits the redundancy of errors and requires only a limited amount of data in the azimuth direction for error estimation. Moreover, the up-sampling operation can be avoided in the combination process. Imaging results based on both simulated and real data are presented to validate the proposed approach. PMID:26131679

  12. Improved specific productivity in cephalexin synthesis by immobilized PGA in silica magnetic micro-particles.

    PubMed

    Bernardino, Susana M S A; Fernandes, Pedro; Fonseca, Luís P

    2010-12-01

    There is a marked trend in pharmaceutical industry towards the replacement of classical organic methods by "green" alternatives that minimize or eliminate the generation of waste and avoid, where possible, the use of toxic and/or hazardous reagents and solvents. In this work the kinetically controlled synthesis of cephalexin by soluble and penicillin G acylase immobilized in sol-gel micro-particles with magnetic properties was performed in aqueous media with PGME and 7-ADCA as substrates, at different concentrations of substrate, temperature, pH, enzyme to substrate ratio and acyl donor to nucleophile ratio. Excess acyl donor had a strong effect on cephalexin productivity. A PGME/7-ADCA ratio of 3 was considered optimum. A maximum specific productivity of 5.9 mmol h(-1), gbiocatalyst(-1) at 160 mM 7-ADCA, 480 mM PGME and low enzyme to substrate ratio at 32.5 U mmol(-1) 7-ADCA was obtained with immobilized PGA in full aqueous medium, suggesting that diffusional limitations were minimized when compared with other commercial biocatalysts. A half-life of 133 h for the immobilized biocatalyst was estimated during cephalexin synthesis in the presence of 100 mM 7-ADCA and 300 mM PGME, in 50 mM Tris/HCl at pH 7.2 and 14°C. These results compare quite favorably with those previously reported for the kinetically controlled synthesis of cephalexin. PMID:20632377

  13. Improved antifungal activity of amphotericin B-loaded TPGS-b-(PCL-ran-PGA) nanoparticles

    PubMed Central

    Tang, Xiaolong; Jiao, Ronghong; Xie, Chunmei; Xu, Lifa; Huo, Zhen; Dai, Jingjing; Qian, Yunyun; Xu, Weiwen; Hou, Wei; Wang, Jiang; Liang, Yong

    2015-01-01

    To develop amphotericin B-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles (PLGA-TPGS-AMB NPs) for fungal infection treatment, PLGA-TPGS NPs and PLGA NPs were synthesized by a modified double emulsion method and characterized in terms of size and size distribution, morphology and zeta potential. Drug encapsulation efficiency, in vitro drug release, and in vitro/vivo tests against Candida glabrata were completed. The data showed that both of the two AMB-loaded NPs (PLGA-AMB NPs, PLGA-TPGS-AMB NPs) achieved significantly higher level of antifungal effects than water suspended AMB. In comparison with PLGA-AMB NPs, PLGA-TPGS-AMB NPs had a stronger protective effect against candidiasis and gained an advantage of prolonged antifungal efficacy. In conclusion, PLGA-TPGS-AMB NPs system significantly improves AMB bioavailability by increasing the aqueous dispersibility and improving the antifungal activity. And this would be an excellent choice for the antifungal treatment of the entrapped drug because of its low toxicity and higher effectiveness. PMID:26131089

  14. A digitally controlled AGC loop circuitry for GNSS receiver chip with a binary weighted accurate dB-linear PGA

    NASA Astrophysics Data System (ADS)

    Gang, Jin; Yiqi, Zhuang; Yue, Yin; Miao, Cui

    2015-03-01

    A novel digitally controlled automatic gain control (AGC) loop circuitry for the global navigation satellite system (GNSS) receiver chip is presented. The entire AGC loop contains a programmable gain amplifier (PGA), an AGC circuit and an analog-to-digital converter (ADC), which is implemented in a 0.18 μm complementary metal-oxide-semiconductor (CMOS) process and measured. A binary-weighted approach is proposed in the PGA to achieve wide dB-linear gain control with small gain error. With binary-weighted cascaded amplifiers for coarse gain control, and parallel binary-weighted trans-conductance amplifier array for fine gain control, the PGA can provide a 64 dB dynamic range from -4 to 60 dB in 1.14 dB gain steps with a less than 0.15 dB gain error. Based on the Gaussian noise statistic characteristic of the GNSS signal, a digital AGC circuit is also proposed with low area and fast settling. The feed-backward AGC loop occupies an area of 0.27 mm2 and settles within less than 165 μs while consuming an average current of 1.92 mA at 1.8 V.

  15. Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles

    PubMed Central

    Qiu, Lixin; Hu, Bicheng; Chen, Hongbo; Li, Shanshan; Hu, Yuqian; Zheng, Yi; Wu, Xinxing

    2015-01-01

    This research was conducted to formulate biodegradable itraconazole (ITZ)-loaded d-a-tocopheryl polyethylene glycol 1000 succinate-b-poly(e-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA); TPP) nanoparticles (NPs) (designed as ITZ-loaded TPP NPs) to improve antifungal efficacy. ITZ-loaded TPP NPs were prepared by a modified double-emulsion method, and their size distribution, morphology, zeta potential, drug encapsulation efficiency, drug-release profile, and antifungal effects were characterized. The cytotoxicity of ITZ-loaded-TPP NPs on HeLa cells and fibroblasts was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The in vivo antifungal activity of ITZ-loaded-TPP NPs was examined in mice by administrating 5×105 colony forming units of Candida albicans through the tail vein. The survival rate and survival time of the mice was observed. The fungal count and pathology of lung tissue was analyzed. The data showed that ITZ-loaded-TPP NPs have size of 265±5.8 nm, zeta potential of −31±0.5 mV, high encapsulation efficiency (95%), and extended drug-release profile. ITZ-loaded-TPP NPs at a high concentration of 25 mg/mL had no cytotoxicity on HeLa cells and fibroblasts. Furthermore, ITZ-loaded-TPP NPs achieved a higher level of antifungal activity both in vitro and in vivo. The survival rate and duration was higher in mice treated by ITZ-loaded-TPP NPs than in the other groups (P<0.05). In conclusion, ITZ-loaded-TPP NPs significantly improved ITZ bioavailability by increasing its aqueous dispersibility and extending the duration of drug release, thereby improving the antifungal efficacy of the ITZ agent. PMID:25733833

  16. Dry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein.

    PubMed

    Kunda, Nitesh K; Alfagih, Iman M; Dennison, Sarah R; Somavarapu, Satyanarayana; Merchant, Zahra; Hutcheon, Gillian A; Saleem, Imran Y

    2015-08-15

    Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64±06.01 nm and zeta-potential: +42.32±02.70 mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01±1.19 μg of BSA per mg of NPs. The BSA adsorbed NPs (5 mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5 mg/ml, corresponding to a ratio of 1:1.5/NP:L-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae<4.46 μm) of 70.67±4.07% and mass median aerodynamic diameter (MMAD) of 2.80±0.21 μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76±03.55% (A549 cell line) at 156.25 μg/ml concentration after 24 h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76±1.54% relative esterolytic activity compared to standard BSA. PMID:26169146

  17. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation

    PubMed Central

    Park, Se-Ho; Hong, Seokmann

    2016-01-01

    Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA) treatment suppresses the development of allergic diseases such as atopic dermatitis (AD). Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT) cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to the design and

  18. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation.

    PubMed

    Park, Hyun Jung; Lee, Sung Won; Park, Se-Ho; Hong, Seokmann

    2016-01-01

    Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA) treatment suppresses the development of allergic diseases such as atopic dermatitis (AD). Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT) cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to the design and

  19. Complete Nucleotide Sequence of pGA45, a 140,698-bp IncFIIY Plasmid Encoding bla IMI-3-Mediated Carbapenem Resistance, from River Sediment.

    PubMed

    Dang, Bingjun; Mao, Daqing; Luo, Yi

    2016-01-01

    Plasmid pGA45 was isolated from the sediments of Haihe River using Escherichia coli CV601 (gfp-tagged) as recipients and indigenous bacteria from sediment as donors. This plasmid confers reduced susceptibility to imipenem which belongs to carbapenem group. Plasmid pGA45 was fully sequenced on an Illumina HiSeq 2000 sequencing system. The complete sequence of plasmid pGA45 was 140,698 bp in length with an average G + C content of 52.03%. Sequence analysis shows that pGA45 belongs to IncFIIY group and harbors a backbone region which shares high homology and gene synteny to several other IncF plasmids including pNDM1_EC14653, pYDC644, pNDM-Ec1GN574, pRJF866, pKOX_NDM1, and pP10164-NDM. In addition to the backbone region, plasmid pGA45 harbors two notable features including one bla IMI-3-containing region and one type VI secretion system region. The bla IMI-3-containing region is responsible for bacteria carbapenem resistance and the type VI secretion system region is probably involved in bacteria virulence, respectively. Plasmid pGA45 represents the first complete nucleotide sequence of the bla IMI-harboring plasmid from environment sample and the sequencing of this plasmid provided insight into the architecture used for the dissemination of bla IMI carbapenemase genes. PMID:26941718

  20. Complete Nucleotide Sequence of pGA45, a 140,698-bp IncFIIY Plasmid Encoding blaIMI-3-Mediated Carbapenem Resistance, from River Sediment

    PubMed Central

    Dang, Bingjun; Mao, Daqing; Luo, Yi

    2016-01-01

    Plasmid pGA45 was isolated from the sediments of Haihe River using Escherichia coli CV601 (gfp-tagged) as recipients and indigenous bacteria from sediment as donors. This plasmid confers reduced susceptibility to imipenem which belongs to carbapenem group. Plasmid pGA45 was fully sequenced on an Illumina HiSeq 2000 sequencing system. The complete sequence of plasmid pGA45 was 140,698 bp in length with an average G + C content of 52.03%. Sequence analysis shows that pGA45 belongs to IncFIIY group and harbors a backbone region which shares high homology and gene synteny to several other IncF plasmids including pNDM1_EC14653, pYDC644, pNDM-Ec1GN574, pRJF866, pKOX_NDM1, and pP10164-NDM. In addition to the backbone region, plasmid pGA45 harbors two notable features including one blaIMI-3-containing region and one type VI secretion system region. The blaIMI-3-containing region is responsible for bacteria carbapenem resistance and the type VI secretion system region is probably involved in bacteria virulence, respectively. Plasmid pGA45 represents the first complete nucleotide sequence of the blaIMI-harboring plasmid from environment sample and the sequencing of this plasmid provided insight into the architecture used for the dissemination of blaIMI carbapenemase genes. PMID:26941718

  1. Investigating the role of source mechanism, surface topography, and attenuation on the observed PGA pattern in May 28, 2004, Mw 6.2 Baladeh earthquake (Iran)

    NASA Astrophysics Data System (ADS)

    Karkooti, Ehsan; Shomali, Zaher Hossein; Pakzad, Mehrdad

    2016-04-01

    In this paper, we use seismic waveform simulation to investigate the influence of source mechanism complexity, surface topography, and quality factor on the observed peak ground motions in May 28, 2004, moment magnitude (Mw) 6.2 Baladeh earthquake. The observed peak ground acceleration (PGA) pattern in this event, which is the biggest earthquake to hit the Central Alborz Mountains of Iran in modern instrumental era, is irregular in some respects. First, the observed PGA contours are elongated toward north-west and, second, the maximum observed PGA value of 1049 cm/s2 on the horizontal component of Hasan Keyf station 50 km away from the epicenter is quite high and irregular for an earthquake of this magnitude, at such long distance. In this study, we employ the spectral element method, implemented in SPECFEM3D software package to simulate the 3D wave propagation from several source models in the area. Our results suggest directivity effect is the main cause of the anomalous observations in this earthquake and could account for the elongation of PGA contours and also the anomalous maximum PGA value observed at Hasan Keyf strong motion station. We show that the surface topography has minor effect on the observed peak ground acceleration and the resulting PGA maps. Also by finding the bounds of seismic quality factor effect on the peak ground acceleration values, we show that this factor could not account for the elongation of iso-acceleration contours in the north-west direction.

  2. The structure of the deacetylase domain of Escherichia coli PgaB, an enzyme required for biofilm formation: a circularly permuted member of the carbohydrate esterase 4 family.

    PubMed

    Nishiyama, Takashi; Noguchi, Hiroki; Yoshida, Hisashi; Park, Sam Yong; Tame, Jeremy R H

    2013-01-01

    Bacterial biofilm formation is an extremely widespread phenomenon involving the secretion of a protective exopolysaccharide matrix which helps the bacteria to attach to surfaces and to overcome a variety of stresses in different environments. This matrix may also include proteins, lipids, DNA and metal ions. Its composition depends on the bacterial species and growth conditions, but one of the most widely found components is polymeric β-1,6-N-acetyl-D-glucosamine (PGA). Several studies have suggested that PGA is an essential component of biofilm and it is produced by numerous bacteria, including Escherichia coli, Staphylococcus epidermis, Yersinia pestis, Bordetella spp. and Actinobacillus spp. In E. coli, PGA production and export are dependent on four genes that form a single operon, pgaABCD, which appears to have been transferred between various species. Biofilms themselves are recognized as environments in which such horizontal gene transfer may occur. The pga operon of E. coli, which is even found in innocuous laboratory strains, is highly homologous to that from the plague bacterium Yersinia pestis, and biofilm is believed to play an important role in the transmission of Yersinia. The crystal structure of the N-terminal domain of PgaB, which has deacetylase activity, is described and compared with models of other deacetylases. PMID:23275162

  3. Effect of biomimetic conditions on mechanical and structural integrity of PGA/P4HB and electrospun PCL scaffolds.

    PubMed

    Klouda, Leda; Vaz, Claudia M; Mol, Anita; Baaijens, Frank P T; Bouten, Carlijn V C

    2008-03-01

    The selection of an appropriate scaffold represents one major key to success in tissue engineering. In cardiovascular applications, where a load-bearing structure is required, scaffolds need to demonstrate sufficient mechanical properties and importantly, reliable retention of these properties during the developmental phase of the tissue engineered construct. The effect of in vitro culture conditions, time and mechanical loading on the retention of mechanical properties of two scaffold types was investigated. First candidate tested was a poly-glycolic acid non-woven fiber mesh, coated with poly-4-hydroxybutyrate (PGA/P4HB), the standard scaffold used successfully in cardiovascular tissue engineering applications. As an alternative, an electrospun poly-epsilon-caprolactone (PCL) scaffold was used. A 15-day dynamic loading protocol was applied to the scaffolds. Additionally, control scaffolds were incubated statically. All studies were performed in a simulated physiological environment (phosphate-buffered saline solution, T=37 degrees C). PGA/P4HB scaffolds showed a dramatic decrease in mechanical properties as a function of incubation time and straining. Mechanical loading had a significant effect on PCL scaffold properties. Degradation as well as fiber fatigue caused by loading promote loss of mechanical properties in PGA/P4HB scaffolds. For PCL, fiber reorganization due to straining seems to be the main reason behind the brittle behavior that was pronounced in these scaffolds. It is suggested that those changes in scaffolds' mechanical properties must be considered at the application of in vitro tissue engineering protocols and should ideally be taken over by tissue formation to maintain mechanically stable tissue constructs. PMID:17701317

  4. Imaging the bone marrow stem cells morphogenesis in PGA scaffold by multiphoton autofluorescence and second harmonic (SHG) imaging

    NASA Astrophysics Data System (ADS)

    Lee, Hsuan-Shu; Teng, Shu-Wen; Chen, Hsiao-Ching; Lo, Wen; Sun, Yen; Lin, Tze-Yu; Chiou, Ling-Ling; Jiang, Ching-Chuan; Dong, Chen-Yuan

    2006-02-01

    The ability to image tissue engineering products without damaging histological procedures is important for the understanding of the dynamics of tissue reorganization and formation. In this work, we test the ability of multiphoton autofluorescence and second harmonic generation microscopy to image engineered tissues following chrondrogenic induction. The system we used is human bone marrow stem cells seeded in the scaffold polyglycolic acid (PGA). Our results show that autofluorescence can be used to image cells while second harmonic generation signal can be used to visualize the synthesis of extracellular matrix. This approach demonstrates the ability of multiphoton imaging in the study of tissue engineering products.

  5. ToF-SIMS evaluation of calcium-containing silica/γ-PGA hybrid systems for bone regeneration

    NASA Astrophysics Data System (ADS)

    Wang, Daming; Nakamura, Jin; Poologasundarampillai, Gowsihan; Kasuga, Toshihiro; Jones, Julian R.; McPhail, David S.

    2014-08-01

    Inorganic/organic hybrids have great potential for the production of bioactive scaffolds which have tailored mechanical properties and degradation rates suitable for tissue engineering. For bone regeneration, calcium incorporation into hybrids at low temperatures is important due to its ability to stimulate new bone formation. As a consequence, understanding the homogeneity of the critical inorganic and organic components will be the key to the development of such hybrids. The aim of this interdisciplinary study was to use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to determine the homogeneity of these critical components. We evaluated various sol-gel silica/γ-polyglutamic acid (γ-PGA) hybrid systems produced using different routes to introduce the calcium, thereby tailoring and optimizing hybrid syntheses and processing routes. Dimethyl carbonate (DMC) was used to improve the inorganic/organic coupling and its influence on the homogeneity of the hybrid structures was also examined. The results revealed that the calcium salt form of γ-PGA was promising for calcium incorporation since homogeneous products could be obtained. The ToF-SIMS data also indicated that the reaction time of hybrid synthesis and the timing of the addition of DMC can affect the homogeneity of hybrids.

  6. HB-EGF embedded in PGA/PLLA scaffolds via subcritical CO2 augments the production of tissue engineered intestine.

    PubMed

    Liu, Yanchun; Nelson, Tyler; Cromeens, Barrett; Rager, Terrence; Lannutti, John; Johnson, Jed; Besner, Gail E

    2016-10-01

    The ability to deliver sustained-release, biologically active growth factors through custom designed tissue engineering scaffolds at sites of tissue regeneration offers great therapeutic opportunity. Due to the short in vivo half-lives of most growth factors, it is challenging to deliver these proteins to sites of interest where they may be used before being degraded. The application of subcritical CO2 uses gas-phase CO2 at subcritical pressures ranging from 41 to 62 bar (595-913 PSI) which avoids foaming by reducing the amount of CO2 dissolved in the polymer and maintains completely reversible plasticization. In the current study, heparin-binding EGF-like growth factor (HB-EGF) was embedded into polyglycolic acid (PGA)/Poly-l-latic acid (PLLA) scaffolds via subcritical CO2 exposure for the production of tissue engineered intestine (TEI). PGA fiber morphology after subcritical CO2 exposure was examined by scanning electron microscopy (SEM) and the distribution of HB-EGF embedded in the scaffold fibers was detected by HB-EGF immunofluorescent staining. In vivo implantation of HB-EGF-embedded scaffolds confirmed significantly improved TEI structure as a result of local delivery of the trophic growth factor. These findings may be critical for the production of TEI in the treatment of patients with short bowel syndrome in the future. PMID:27380441

  7. A comparative study of different PGA attenuation and error models: Case of 1999 Chi-Chi earthquake

    NASA Astrophysics Data System (ADS)

    Mebarki, Ahmed

    2009-03-01

    In order to evaluate the horizontal peak ground acceleration (HPGA) during earthquakes, the author studies the respective efficiency of two existing attenuation models [Mébarki, A., 2003a, Risques sismiques: aléas, vulnérabilité et aide à la décision par cartes SIG. Proceedings of International Conference on "Risks, Vulnerability and Reliability in Construction. Towards a reduction of disasters". ISBN: 9961-891-01-5, pp. 82-97. Algiers, October 11-12, Mébarki, A., 2003b. Proposal of a parametric attenuation model and comparison with some worldwide earthquakes. VII o Congreso Venezolano de Sismologia y Ingenieria Sísmica, Barquisimeto, Venezuela. November 12-13, (CD-ROM), Mébarki A., 2004. Modèle d'atténuation sismique: prédiction probabiliste des pics d'accélération, RFGC — Revue Française de Génie Civil, Hermès Ed., 8 (9-10), 1071-1086]. A comparative study of their performances is done in the case of 1999 Chi-Chi earthquake (Taiwan). The reported PGA (Peak Ground Accelerations) values correspond to hypocentral distances ranging from 15 up to 180 km with observed acceleration peaks ranging from (0.04 g) up to (1.16 g). The author considers two kinds of probabilistic distributions for the error model in order to describe the uncertainty and the variability that affect the values of the PGA: a Gamma distribution and a Log-normal distribution. The adopted error models assume that the variability of the PGA is such that its coefficient of variation is equal to 55% [Mébarki, A., 2003a. Risques sismiques: aléas, vulnérabilité et aide à la décision par cartes SIG. Proceedings of International Conference on "Risks, Vulnerability and Reliability in Construction. Towards a reduction of disasters". ISBN: 9961-891-01-5, pp. 82-97. Algiers, October 11-12, Mébarki, A., 2003b. Proposal of a parametric attenuation model and comparison with some worldwide earthquakes. VII o Congreso Venezolano de Sismologia y Ingenieria Sísmica, Barquisimeto, Venezuela

  8. A Study of the Oxidation Behaviour of Pile Grade A (PGA) Nuclear Graphite Using Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) and X-Ray Tomography (XRT).

    PubMed

    Payne, Liam; Heard, Peter J; Scott, Thomas B

    2015-01-01

    Pile grade A (PGA) graphite was used as a material for moderating and reflecting neutrons in the UK's first generation Magnox nuclear power reactors. As all but one of these reactors are now shut down there is a need to understand the residual state of the material prior to decommissioning of the cores, in particular the location and concentration of key radio-contaminants such as 14C. The oxidation behaviour of unirradiated PGA graphite was studied, in the temperature range 600-1050°C, in air and nitrogen using thermogravimetric analysis, scanning electron microscopy and X-ray tomography to investigate the possibility of using thermal degradation techniques to examine 14C distribution within irradiated material. The thermal decomposition of PGA graphite was observed to follow the three oxidation regimes historically identified by previous workers with limited, uniform oxidation at temperatures below 600°C and substantial, external oxidation at higher temperatures. This work demonstrates that the different oxidation regimes of PGA graphite could be developed into a methodology to characterise the distribution and concentration of 14C in irradiated graphite by thermal treatment. PMID:26575374

  9. A Study of the Oxidation Behaviour of Pile Grade A (PGA) Nuclear Graphite Using Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) and X-Ray Tomography (XRT)

    PubMed Central

    Payne, Liam; Heard, Peter J.; Scott, Thomas B.

    2015-01-01

    Pile grade A (PGA) graphite was used as a material for moderating and reflecting neutrons in the UK’s first generation Magnox nuclear power reactors. As all but one of these reactors are now shut down there is a need to understand the residual state of the material prior to decommissioning of the cores, in particular the location and concentration of key radio-contaminants such as 14C. The oxidation behaviour of unirradiated PGA graphite was studied, in the temperature range 600–1050°C, in air and nitrogen using thermogravimetric analysis, scanning electron microscopy and X-ray tomography to investigate the possibility of using thermal degradation techniques to examine 14C distribution within irradiated material. The thermal decomposition of PGA graphite was observed to follow the three oxidation regimes historically identified by previous workers with limited, uniform oxidation at temperatures below 600°C and substantial, external oxidation at higher temperatures. This work demonstrates that the different oxidation regimes of PGA graphite could be developed into a methodology to characterise the distribution and concentration of 14C in irradiated graphite by thermal treatment. PMID:26575374

  10. 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

  11. Surface modification of TPGS- b-(PCL- ran-PGA) nanoparticles with polyethyleneimine as a co-delivery system of TRAIL and endostatin for cervical cancer gene therapy

    NASA Astrophysics Data System (ADS)

    Zheng, Yi; Chen, Hongbo; Zeng, Xiaowei; Liu, Zhigang; Xiao, Xiaojun; Zhu, Yongqiang; Gu, Dayong; Mei, Lin

    2013-04-01

    The efficient delivery of therapeutic genes into cells of interest is a critical challenge to broad application of non-viral vector systems. In this research, a novel TPGS- b-(PCL- ran-PGA) nanoparticle modified with polyethyleneimine was applied to be a vector of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin for cervical cancer gene therapy. Firstly, a novel biodegradable copolymer, TPGS- b-(PCL- ran-PGA), was synthesized and characterized. The nanoparticles were fabricated by an emulsion/solvent evaporation method and then further modified with polyethyleneimine (PEI) carrying TRAIL and/or endostatin genes. The uptake of pIRES2-EGFP and/or pDsRED nanoparticles by HeLa cells were observed by fluorescence microscopy and confocal laser scanning microscopy. The cell viability of TRAIL/endostatin-loaded nanoparticles in HeLa cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide assay. Severe combined immunodeficient mice carrying HeLa tumor xenografts were treated in groups of six including phosphate-buffered saline control, blank TPGS- b-(PCL- ran-PGA) nanoparticles, blank TPGS- b-(PCL- ran-PGA)/PEI nanoparticles, and three types of gene nanoparticles. The activity was assessed using average increase in survival time, body weight, and solid tumor volume. All the specimens were then prepared as formalin-fixed and paraffin-embedded tissue sections for hematoxylin-eosin staining. The data showed that the nanoparticles could efficiently deliver plasmids into HeLa cells. The cytotoxicity of the HeLa cells was significantly increased by TRAIL/endostatin-loaded nanoparticles when compared with control groups. The use of TPGS in combination with TRAIL and endostatin had synergistic antitumor effects. In conclusion, the TRAIL/endostatin-loaded nanoparticles offer considerable potential as an ideal candidate for in vivo cancer gene delivery.

  12. Abundance analysis, spectral variability, and search for the presence of a magnetic field in the typical PGa star HD 19400

    NASA Astrophysics Data System (ADS)

    Hubrig, S.; Castelli, F.; González, J. F.; Carroll, T. A.; Ilyin, I.; Schöller, M.; Drake, N. A.; Korhonen, H.; Briquet, M.

    2014-08-01

    The aim of this study is to carry out an abundance determination, to search for spectral variability and for the presence of a weak magnetic field in the typical PGa star HD 19400. High-resolution, high signal-to-noise High Accuracy Radial-velocity Planet Searcher (HARPS) spectropolarimetric observations of HD 19400 were obtained at three different epochs in 2011 and 2013. For the first time, we present abundances of various elements determined using an ATLAS12 model, including the abundances of a number of elements not analysed by previous studies, such as Ne I, Ga II, and Xe II. Several lines of As II are also present in the spectra of HD 19400. To study the variability, we compared the behaviour of the line profiles of various elements. We report on the first detection of anomalous shapes of line profiles belonging to Mn and Hg, and the variability of the line profiles belonging to the elements Hg, P, Mn, Fe, and Ga. We suggest that the variability of the line profiles of these elements is caused by their non-uniform surface distribution, similar to the presence of chemical spots detected in HgMn stars. The search for the presence of a magnetic field was carried out using the moment technique and the Singular Value Decomposition (SVD) method. Our measurements of the magnetic field with the moment technique using 22 Mn II lines indicate the potential existence of a weak variable longitudinal magnetic field on the first epoch. The SVD method applied to the Mn II lines indicates = -76 ± 25 G on the first epoch, and at the same epoch the SVD analysis of the observations using the Fe II lines shows = -91 ± 35 G. The calculated false alarm probability values, 0.008 and 0.003, respectively, are above the value 10-3, indicating no detection.

  13. Ge Nanocluster Enhanced Er Photoluminescence

    NASA Astrophysics Data System (ADS)

    Guzman, Julian; Chrzan, Daryl C.; Haller, Eugene E.

    2010-03-01

    We investigated the enhancement of the Er^3+ photoluminescence (PL) at 1540 nm by the incorporation of Ge nanoclusters into Er-doped silica using ion beams. We found that the Er^3+ PL enhancement is due to the presence of Ge and not to the radiation damage from the ion-implantation process. We determined that the Er^3+ PL depends on the Ge content, postgrowth annealing, and crystallinity of the Ge nanoclusters. Furthermore, we observed that the Er^3+ PL signal is maximized after annealing at 685 C for 1 h. This is the temperature at which Ge nanoclusters begin to crystallize. Transmission electron microscopy studies were conducted to determine the size distribution of the Ge nanoclusters. Moreover, extended X-ray absorption fine structure measurements performed at the Ge-K and Er-LIII edges revealed that there is negligible Ge-Er bonding. This suggests that Er is either fully oxidized or that it is not located in the Ge nanoclusters. Therefore, we believe that the energy transfer process from the Ge nanoclusters to the Er ions occurs through a non-optical resonant dipole transfer (F"orster ProcessfootnotetextT. F"orster, Discuss. Faraday Soc. 27, 7 (1959). similar to what has been proposed for the Si nanocrystal case.footnotetextM. Fujii, M. Yoshida, S. Hayashi, and K. Yamamoto, J. Appl. Phys. 84, 4525 (1998).

  14. Characterization of GaN nanowires grown on PSi, PZnO and PGaN on Si (111) substrates by thermal evaporation

    NASA Astrophysics Data System (ADS)

    Shekari, Leila; Hassan, Haslan Abu; Thahab, Sabah M.; Hassan, Zainuriah

    2012-06-01

    In this research, we used an easy and inexpensive method to synthesize highly crystalline GaN nanowires (NWs); on different substrates such as porous silicon (PSi), porous zinc oxide (PZnO) and porous gallium nitride (PGaN) on Si (111) wafer by thermal evaporation using commercial GaN powder without any catalyst. Micro structural studies by scanning electron microscopy and transmission electron microscope measurements reveal the role of different substrates in the morphology, nucleation and alignment of the GaN nanowires. The degree of alignment of the synthesized nanowires does not depend on the lattice mismatch between wires and their substrates. Further structural and optical characterizations were performed using high resolution X-ray diffraction and energy-dispersive X-ray spectroscopy. Results indicate that the nanowires are of single-crystal hexagonal GaN. The quality and density of grown GaN nanowires for different substrates are highly dependent on the lattice mismatch between the nanowires and their substrates and also on the size of the porosity of the substrates. Nanowires grown on PGaN have the best quality and highest density as compared to nanowires on other substrates. By using three kinds of porous substrates, we are able to study the increase in the alignment and density of the nanowires.

  15. Characterization of GaN nanowires grown on PSi, PZnO and PGaN on Si (111) substrates by thermal evaporation

    SciTech Connect

    Shekari, Leila; Hassan, Haslan Abu; Thahab, Sabah M.; Hassan, Zainuriah

    2012-06-20

    In this research, we used an easy and inexpensive method to synthesize highly crystalline GaN nanowires (NWs); on different substrates such as porous silicon (PSi), porous zinc oxide (PZnO) and porous gallium nitride (PGaN) on Si (111) wafer by thermal evaporation using commercial GaN powder without any catalyst. Micro structural studies by scanning electron microscopy and transmission electron microscope measurements reveal the role of different substrates in the morphology, nucleation and alignment of the GaN nanowires. The degree of alignment of the synthesized nanowires does not depend on the lattice mismatch between wires and their substrates. Further structural and optical characterizations were performed using high resolution X-ray diffraction and energy-dispersive X-ray spectroscopy. Results indicate that the nanowires are of single-crystal hexagonal GaN. The quality and density of grown GaN nanowires for different substrates are highly dependent on the lattice mismatch between the nanowires and their substrates and also on the size of the porosity of the substrates. Nanowires grown on PGaN have the best quality and highest density as compared to nanowires on other substrates. By using three kinds of porous substrates, we are able to study the increase in the alignment and density of the nanowires.

  16. 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.

  17. The Structure- and Metal-dependent Activity of Escherichia coli PgaB Provides Insight into the Partial De-N-acetylation of Poly-β-1,6-N-acetyl-d-glucosamine*

    PubMed Central

    Little, Dustin J.; Poloczek, Joanna; Whitney, John C.; Robinson, Howard; Nitz, Mark; Howell, P. Lynne

    2012-01-01

    Exopolysaccharides are required for the development and integrity of biofilms produced by a wide variety of bacteria. In Escherichia coli, partial de-N-acetylation of the exopolysaccharide poly-β-1,6-N-acetyl-d-glucosamine (PNAG) by the periplasmic protein PgaB is required for polysaccharide intercellular adhesin-dependent biofilm formation. To understand the molecular basis for PNAG de-N-acetylation, the structure of PgaB in complex with Ni2+ and Fe3+ have been determined to 1.9 and 2.1 Å resolution, respectively, and its activity on β-1,6-GlcNAc oligomers has been characterized. The structure of PgaB reveals two (β/α)x barrel domains: a metal-binding de-N-acetylase that is a member of the family 4 carbohydrate esterases (CE4s) and a domain structurally similar to glycoside hydrolases. PgaB displays de-N-acetylase activity on β-1,6-GlcNAc oligomers but not on the β-1,4-(GlcNAc)4 oligomer chitotetraose and is the first CE4 member to exhibit this substrate specificity. De-N-acetylation occurs in a length-dependent manor, and specificity is observed for the position of de-N-acetylation. A key aspartic acid involved in de-N-acetylation, normally seen in other CE4s, is missing in PgaB, suggesting that the activity of PgaB is attenuated to maintain the low levels of de-N-acetylation of PNAG observed in vivo. The metal dependence of PgaB is different from most CE4s, because PgaB shows increased rates of de-N-acetylation with Co2+ and Ni2+ under aerobic conditions, and Co2+, Ni2+ and Fe2+ under anaerobic conditions, but decreased activity with Zn2+. The work presented herein will guide inhibitor design to combat biofilm formation by E. coli and potentially a wide range of medically relevant bacteria producing polysaccharide intercellular adhesin-dependent biofilms. PMID:22810235

  18. Fractional spin textures in the frustrated magnet SrCr(9p)Ga(12-9p)O₁₉.

    PubMed

    Sen, Arnab; Damle, Kedar; Moessner, Roderich

    2011-03-25

    We consider the archetypal frustrated antiferromagnet SrCr(9p)Ga(12-9p)O₁₉ in its well-known spin-liquid state, and demonstrate that a Cr(3+) spin S=3/2 ion in direct proximity to a pair of vacancies (in disordered p<1 samples) is cloaked by a spatially extended spin texture that encodes the correlations of the parent spin liquid. In this spin-liquid regime, our analytic theory predicts that the combined object has a magnetic response identical to a classical spin of length S/2=3/4, which dominates over the small intrinsic susceptibility of the pure system. This fractional-spin texture leaves an unmistakable imprint on the measured ⁷¹Ga nuclear magnetic resonance line shapes, which we compute using Monte Carlo simulations and compare with experimental data. PMID:21517349

  19. Ames ER-2 ozone measurements

    NASA Technical Reports Server (NTRS)

    Pearson, R., Jr.; Vedder, James F.; Starr, W. L.

    1990-01-01

    The objective of this research is to study ozone (O3) in the stratosphere. Measurements of the ozone mixing ratio at 1 s intervals are obtained with an ultraviolet photometer which flies on the ER-2 aircraft. The photometer determines the amount of ozone in air by measuring the transmission of ultraviolet light through a fixed path with and without ambient O3 present.

  20. 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.

  1. ERS Focus On: Educating Boys

    ERIC Educational Resources Information Center

    Clarke, Suzanne

    2007-01-01

    This issue of "Focus On" examines where boys are underachieving and some possible reasons for their under-achievement, including biological and environmental factors. It also offers strategies that teachers can employ in their classrooms in order to address the educational needs of boys. Books in Brief; Web Resources; and Related ERS Resources are…

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. UBV photometry of ER Vulpeculae

    NASA Astrophysics Data System (ADS)

    Srivastava, R. K.; Padalia, T. D.; Srivastava, J. B.

    1991-08-01

    UBV photometry of the RS CVn-type eclipsing binary system ER Vulpeculae has been presented. The period comes out to be 0.698093d. The average depths of primary and secondary minima are, respectively, 0.21 and 0.12m. The colors at various phases have been given. A dip is seen around phase 0.73P as was seen in the observations of Arevalo et al. (1988). Large scatter is present in the observations as noticed earlier, and may be due to activity of the components.

  7. Next Generation Attenuation of Ground Motions in Ilan, Taiwan: Establishment and Analysis of Attenuation Relations for Peak Ground Acceleration (PGA) and Peak Ground Velocity (PGV)

    NASA Astrophysics Data System (ADS)

    Liu, K.

    2009-12-01

    An evaluation of seismic hazards requires an estimate of the expected ground motion at the site of interest. The most common means of estimating this ground motion in engineering practice is the use of an attenuation relation. A number of developments have arisen recently to suggest that a new generation of attenuation relationships is warranted. The project named Next Generation Attenuation of Ground Motions (NGA) Project was developed by Pacific Earthquake Engineering Research Center (PEER) in response to a core objective: reducing uncertainty in earthquake ground motion estimation. This objective reflects recognition from industry sponsors that improvements in earthquake ground motion estimation will result in significant cost savings and will result in improved system performance in the event of a large earthquake. The Central Weather Bureau has implemented the Taiwan Strong Motion Instrumentation Program (TSMIP) to collect high-quality instrumental recordings of strong earthquake shaking.It is necessary for us to study the strong ground motion characteristics at the Ilan area of northeastern Taiwan. Further analyses using a good quality data base that includes 486 events and 4172 recordings of magnitude greater than 4.0 are required to derive the next generation attenuation of ground motion in Ilan area. In addition, Liu and Tsai (2007) used a catalog of more than 1840 shallow earthquakes with homogenized Mw magnitude ranging from 5.0 to 8.2 in 1900-2007 to estimate the seismic hazard potential in Taiwan. As a result, the PGA and PGV contour patterns of maximum ground motion show that Ilan Plain has high values of 0.2g and 80cm/sec with respect to MMI intensity VII and IX, respectively. Furthermore, from the mean ground motion and the seismic intensity rate analyses, they show that a high annul probability of MMI > VI greater than 35 percents are located at the Chianan area of western Taiwan and Ilan Plain in northeastern Taiwan. However, these results was

  8. 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

  9. Luminescence and Thermal Properties of Er:GSGG and Yb,Er:GSGG Laser Crystals

    NASA Astrophysics Data System (ADS)

    Sun, Dun-Lu; Luo, Jian-Qiao; Xiao, Jing-Zhong; Zhang, Qing-Li; Chen, Jia-Kang; Liu, Wen-Peng; Kang, Hong-Xiang; Yin, Shao-Tang

    2012-05-01

    Er3+-doped and Yb3+/Er3+ co-doped Gd3Sc2Ga3O12 (abbreviated as Er:GSGG and Yb,Er:GSGG, respectively) laser crystals are investigated by using a combination of spectroscopic measurements and thermal characterizations. An absorption peak of Yb,Er:GSGG crystal shifts to 970 nm and its absorption band broadens obviously, which makes the crystal suitable for pumping by a 970 nm laser diode (LD). This crystal also exhibits a shorter lifetime of a lower laser level, a larger emission cross section and higher thermal conductivity than those of Er:GSGG. All these factors suggest that Yb3+/Er3+ co-doping has a positive effect on improving the spectroscopic and thermal performances in GSGG based laser crystals, and imply that double-doped Yb,Er:GSGG crystal is a potential candidate as an excellent LD pumped 2.79 μm laser material.

  10. Understanding the Magnitude Dependence of PGA and PGV: A look at differences between mainshocks and aftershocks in the NGA-West2 data and ground motion from small magnitude Anza data

    NASA Astrophysics Data System (ADS)

    Baltay, A.; Hanks, T. C.

    2013-12-01

    We build an earthquake-source based model to explain the magnitude dependence of PGA (peak ground acceleration) and PGV (peak ground velocity) observable in the NGA-West2 ground motion database and empirically based ground motion prediction equations (GMPEs). This simple model is based on a point-source, constant stress drop (Δσ) Brune model, including the high-frequency attenuation parameter (fmax or κ), random vibration theory (RVT) and a finite-fault assumption. This simple approach explains the magnitude dependence of PGA and PGV in the NGA-West2 ground motion data, and matches the GMPEs well. Using this model as a reference condition, we explore secondary dependencies, such as the difference in ground motion between mainshocks and aftershocks, and the magnitude dependence of ground motion from small magnitude earthquakes. In the NGA-West2 database, which consists of over 20,000 records of events from 3< M < 8, mainshocks are defined as Class 1 events, and on-fault aftershocks as Class 2. By comparing the median ground motion of these events with our source-based model, we can distinguish overall differences in stress drop associated with Class 1 vs. Class 2 events. We find that when taken all together, Class 2 events have slightly lower stress drop than Class 1 events. This suggests that the Class 2 events, on-fault aftershocks, may be re-rupturing damaged fault areas yielding lower stress drops. We observe more scatter in this model-based stress drop for the Class 2 events as compared to the mainshocks, similar to what is observed in seismologically based source studies. We also consider the magnitude dependence of very small magnitude data, 0PGA and PGV on magnitude, a consistent magnitude scale is necessary. Anza data are typically reported with local magnitude, ML, so we make a theoretically based empirical correction to convert to moment magnitude M. The

  11. 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.

  12. 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.

  13. Are Wnts Retrogradely Transported to the ER?

    PubMed

    Tang, Bor Luen

    2016-11-01

    A recent report showed that Drosophila miR-307a initiates endoplasmic reticulum (ER) stress in wingless (wg)-expressing cells by suppression of the evolutionarily conserve Wnt secretion factor Wntless (Wls). Interestingly, the authors noted that wg has a putative C-terminal dilysine motif (KKVY), which is required for its apparent retrograde Golgi-to-ER transport. Wls suppression resulted in ER stress, which was phenocopied by several other manipulations that impaired wg secretion in flies, as well as Wnt5a secretion in mammalian cells. The authors surmised that their data "reveals a previously unknown Golgi-to-ER retrograde route of wg, and elucidates a correlation between Wnt secretion and ER stress." However, there are obvious caveats to this interpretation, as ER stress resulting from Wnt secretion impairment could be readily explained by its inability to leave the ER, and not resulting from Golgi-to-ER retrograde transport. J. Cell. Physiol. 231: 2315-2316, 2016. © 2016 Wiley Periodicals, Inc. PMID:26916992

  14. 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.

  15. 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.

  16. Facilitative plasma membrane transporters function during ER transit

    PubMed Central

    Takanaga, Hitomi; Frommer, Wolf B.

    2010-01-01

    Although biochemical studies suggested a high permeability of the endoplasmic reticulum (ER) membrane for small molecules, proteomics identified few specialized ER transporters. To test functionality of transporters during ER passage, we tested whether glucose transporters (GLUTs, SGLTs) destined for the plasma membrane are active during ER transit. HepG2 cells were characterized by low-affinity ER transport activity, suggesting that ER uptake is protein mediated. The much-reduced capacity of HEK293T cells to take up glucose across the plasma membrane correlated with low ER transport. Ectopic expression of GLUT1, -2, -4, or -9 induced GLUT isoform-specific ER transport activity in HEK293T cells. In contrast, the Na+-glucose cotransporter SGLT1 mediated efficient plasma membrane glucose transport but no detectable ER uptake, probably because of lack of a sufficient sodium gradient across the ER membrane. In conclusion, we demonstrate that GLUTs are sufficient for mediating ER glucose transport en route to the plasma membrane. Because of the low volume of the ER, trace amounts of these uniporters contribute to ER solute import during ER transit, while uniporters and cation-coupled transporters carry out export from the ER, together potentially explaining the low selectivity of ER transport. Expression levels and residence time of transporters in the ER, as well as their coupling mechanisms, could be key determinants of ER permeability.—Takanaga, H., Frommer, W. B. Facilitative plasma membrane transporters function during ER transit. PMID:20354141

  17. 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 ...

  18. Edible Pot Sends Toddlers to Colorado ERs

    MedlinePlus

    ... html Edible Pot Sends Toddlers to Colorado ERs Cannabis-laced candy, baked goods look irresistible to kids, ... became the first two states to legalize recreational marijuana. Shortly after, a sharp increase occurred in the ...

  19. Environmental release summary (ERS) database CY 1997

    SciTech Connect

    Gleckler, B.P.

    1998-07-01

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

  20. FIRE_ACE_ER2_MAS

    Atmospheric Science Data Center

    2015-10-28

    ... First ISCCP Regional Experiment (FIRE) Arctic Cloud Experiment (ACE) NASA ER-2 Moderate Resolution Imaging ... SSFR Location:  Northern Alaska Arctic Ocean Spatial Coverage:  Fairbanks, Alaska and the surrounding ...

  1. Characterization of the ER-Targeted Low Affinity Ca(2+) Probe D4ER.

    PubMed

    Greotti, Elisa; Wong, Andrea; Pozzan, Tullio; Pendin, Diana; Pizzo, Paola

    2016-01-01

    Calcium ion (Ca(2+)) is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER) represents the major intracellular Ca(2+) store and the free Ca(2+) concentration ([Ca(2+)]) within its lumen ([Ca(2+)]ER) can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca(2+) sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca(2+) probes are plagued by different drawbacks, such as a double dissociation constant (Kd) for Ca(2+), low dynamic range, and an affinity for the cation that is too high for the levels of [Ca(2+)] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET)-based, Cameleon probe, named D4ER, characterized by suitable Ca(2+) affinity and dynamic range for monitoring [Ca(2+)] variations within the ER. As an example, resting [Ca(2+)]ER have been evaluated in a known paradigm of altered ER Ca(2+) homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer's Disease-linked protein Presenilin 2 (PS2). The lower Ca(2+) affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca(2+) content in cells expressing mutated PS2, compared to controls. PMID:27598166

  2. 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.

  3. Arctigenin alleviates ER stress via activating AMPK

    PubMed Central

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  4. Recent Advances with ER Targeted Intrabodies.

    PubMed

    Marschall, Andrea L J; Dübel, Stefan; Böldicke, Thomas

    2016-01-01

    ER intrabodies are recombinant antibody fragments produced and retained in the endoplasmatic reticulum (ER) of a cell or an organism with the purpose to induce phenotypes generated by interfering with the intracellular processing or by changing the location of the recognized antigen. The most common application is the generation of functional knockdowns of membrane proteins, which cannot reach their natural location on the cell surface when they are retained in the ER by the intrabody. Phenotypes generated by interfering with the secretion of extracellular or plasma proteins can be analyzed in a similar way. So far, most ER intrabody studies relied on scFv fragments subcloned from hybridoma lines. Recently, several large international research consortia have started to provide antibodies, with the final goal to cover substantial parts of the human proteome. For practical reasons of throughput and effort, in these consortia the most appropriate method to generate the necessary large numbers of monoclonal antibodies is in vitro selection, typically employing phage or yeast display. These methods provide the antibody genes right from the start, thereby facilitating the application of ER antibody approaches. On the other end, the first transgenic mice expressing an ER intrabody has recently been described. This moves the ER intrabody approach finally to level with classic in vivo knockout strategies - but also offers novel capabilities to the researchers. Promising new perspectives may originate from the fact that the knockdown is restricted to the protein level, that a graded knockdown strength can be achieved, or that the targeting of individual posttranslational modifications will be possible with previously impossible specificity. Finally, the link of today's high throughput recombinant antibody generation to a knock down phenotype is now possible with a single cloning step. It can therefore be expected that we will see a much quicker growth of the number of

  5. 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

  6. 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.

  7. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  8. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  9. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  10. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  11. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  12. 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.

  13. 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

  14. 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...

  15. 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…

  16. European Space Agency, ERS-1 program

    NASA Technical Reports Server (NTRS)

    Haskell, A.

    1983-01-01

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

  17. Er3+ fluorescence in rare-earth aluminate glass

    NASA Astrophysics Data System (ADS)

    Weber, Richard; Hampton, Scott; Nordine, Paul C.; Key, Thomas; Scheunemann, Richard

    2005-08-01

    Er3+ ion fluorescence was excited with a 980-nm pump laser in Er-doped rare-earth aluminate (REAl) glasses with Er-dopant concentrations from 0.5-30mol% (oxides basis). The spectral and decay characteristics were measured at ˜1550nm from Er3+I13/24 and at ˜2750nm from Er3+I11/24. Red and green light emissions were also observed, from Er3+F9/24 and S3/24+H11/22, respectively. The fluorescence decay rates are described by a model that yields an accurate fit of results at Er concentrations from 0.5to7mol%. The radiative lifetime of Er3+I13/24 in Er:REAl glass is 6.12±0.26ms. Hydroxyl ion quenching occurs at a rate given by 9.88×10-20 aOHnEr Hz, where aOH is the glass absorption coefficient (in cm-1) at a wavelength of 2950nm and nEr is the total Er ion concentration. The I13/24 upconversion rate constant increases with the Er concentration to 1.35+0.05×10-18width="0.3em"/>cm3/s at and above 7-mol% Er2O3. Er3+I11/24 fluorescence decays primarily by multiphonon quenching to I13/24, at 7700±800Hz, a rate that is slightly less than in tellurite glasses. The addition of 20-mol% silica to the glass has only a small influence on the fluorescence decay rates and greatly improves glass formation from the liquid to allow melting and casting of Er-doped REAl glass from platinum crucibles. The application of these Er-doped glasses in laser and optical device applications is briefly discussed.

  18. Lattice and magnetic properties of ErVO4 and ErPO4

    NASA Astrophysics Data System (ADS)

    Hirano, Y.; Skanthakumar, S.; Loong, C.-K.; Wakabayashi, N.; Boatner, L. A.

    2002-07-01

    The crystal-field energy-level structure of the Er3+ ground-state multiplet in ErVO4 was investigated by inelastic neutron scattering and magnetic susceptibility methods. The quantitative determination of the crystal-field-level energetics in conjunction with elastic-constant data was used to carry out a detailed analysis of the magnetoelastic contribution to the temperature dependence of the lattice parameters. X-ray-diffraction measurements show that the magnetoelastic effect is small, but the anisotropy with respect to the tetragonal c axis is unusual among the rare-earth orthovanadate and orthophosphate series. It was concluded that in ErVO4 the sixth-order multipole contribution is essential for explaining the observed thermal-expansion anomaly. A similar situation also occurs in the case of ErPO4. This result is contrary to the dominating role of the quadrupole effect found previously in many rare-earth orthovanadates and orthophosphates.

  19. 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

  20. 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

  1. 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

  2. Ethylene Perception by the ERS1 Protein in Arabidopsis1

    PubMed Central

    Hall, Anne E.; Findell, Jennifer L.; Schaller, G. Eric; Sisler, Edward C.; Bleecker, Anthony B.

    2000-01-01

    Ethylene perception in Arabidopsis is controlled by a family of five genes, including ETR1, ERS1 (ethylene response sensor 1), ERS2, ETR2, and EIN4. ERS1, the most highly conserved gene with ETR1, encodes a protein with 67% identity to ETR1. To clarify the role of ERS1 in ethylene sensing, we biochemically characterized the ERS1 protein by heterologous expression in yeast. ERS1, like ETR1, forms a membrane-associated, disulfide-linked dimer. In addition, yeast expressing the ERS1 protein contains ethylene-binding sites, indicating ERS1 is also an ethylene-binding protein. This finding supports previous genetic evidence that isoforms of ETR1 also function in plants as ethylene receptors. Further, we used the ethylene antagonist 1-methylcyclopropene (1-MCP) to characterize the ethylene-binding sites of ERS1 and ETR1. We found 1-MCP to be both a potent inhibitor of the ethylene-induced seedling triple response, as well as ethylene binding by yeast expressing ETR1 and ERS1. Yeast expressing ETR1 and ERS1 showed nearly identical sensitivity to 1-MCP, suggesting that the ethylene-binding sites of ETR1 and ERS1 have similar affinities for ethylene. PMID:10938361

  3. Ground-motion prediction equations for the average horizontal component of PGA, PGV, and 5%-damped PSA at spectral periods between 0.01 s and 10.0 s

    USGS Publications Warehouse

    Boore, D.M.; Atkinson, G.M.

    2008-01-01

    This paper contains ground-motion prediction equations (GMPEs) for average horizontal-component ground motions as a function of earthquake magnitude, distance from source to site, local average shear-wave velocity, and fault type. Our equations are for peak ground acceleration (PGA), peak ground velocity (PGV), and 5%-damped pseudo-absolute-acceleration spectra (PSA) at periods between 0.01 s and 10 s. They were derived by empirical regression of an extensive strong-motion database compiled by the 'PEER NGA' (Pacific Earthquake Engineering Research Center's Next Generation Attenuation) project. For periods less than 1 s, the analysis used 1,574 records from 58 mainshocks in the distance range from 0 km to 400 km (the number of available data decreased as period increased). The primary predictor variables are moment magnitude (M), closest horizontal distance to the surface projection of the fault plane (RJB), and the time-averaged shear-wave velocity from the surface to 30 m (VS30). The equations are applicable for M=5-8, RJB<200 km, and VS30= 180-1300 m/s. ?? 2008, Earthquake Engineering Research Institute.

  4. 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).

  5. Meyers Großer Sternenatlas

    NASA Astrophysics Data System (ADS)

    Brunier, Serge; Fujii, Akira

    Unendliche Weiten mal ganz aus der Nähe betrachtet. Meyers Großer Sternenatlas ist ein außergewöhnlicher Bildband über den Sternenhimmel, der die Sternbilder erstmals im gleichen Größenverhältnis zeigt, wie sie am Himmel erscheinen. Die sensationellen Astrofotos und aktuellen Aufnahmen des Hubble-Weltraumteleskops werden Gelegenheitsbeobachter und Hobbyastronomen gleichermaßen begeistern.

  6. 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

  7. Optical properties of RbMnF3:Er3+

    NASA Astrophysics Data System (ADS)

    Iverson, M. V.; Sibley, W. A.

    1980-03-01

    Absorption, emission, excitation, and lifetime data are presented for RbMnF3:Er3+. Evidence for Mn2+ --> Er3+ energy transfer was found from the Er3+ excitation spectra and the temperature dependence of the Mn2+ and Er3+ emissions. The presence of Er3+ in the lattice slightly changed the temperature dependence of the Mn2+ lifetime. Radiative and radiationless transitions are discussed in terms of the model of Flaherty and Di Bartolo and the quantum-mechanical single-configuration coordinate model of Struck and Fonger.

  8. 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

  9. 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.

  10. The role of ER stress in lipid metabolism and lipotoxicity.

    PubMed

    Han, Jaeseok; Kaufman, Randal J

    2016-08-01

    The endoplasmic reticulum (ER) is a cellular organelle important for regulating calcium homeostasis, lipid metabolism, protein synthesis, and posttranslational modification and trafficking. Numerous environmental, physiological, and pathological insults disturb ER homeostasis, referred to as ER stress, in which a collection of conserved intracellular signaling pathways, termed the unfolded protein response (UPR), are activated to maintain ER function for cell survival. However, excessive and/or prolonged UPR activation leads to initiation of self-destruction through apoptosis. Excessive accumulation of lipids and their intermediate products causes metabolic abnormalities and cell death, called lipotoxicity, in peripheral organs, including the pancreatic islets, liver, muscle, and heart. Because accumulating evidence links chronic ER stress and defects in UPR signaling to lipotoxicity in peripheral tissues, understanding the role of ER stress in cell physiology is a topic under intense investigation. In this review, we highlight recent findings that link ER stress and UPR signaling to the pathogenesis of peripheral organs due to lipotoxicity. PMID:27146479

  11. Ternary system Er-Ni-In at T=870 K

    SciTech Connect

    Dzevenko, M.; Tyvanchuk, Yu.; Bratash, L.; Zaremba, V.; Havela, L.; Kalychak, Ya.

    2011-10-15

    Isothermal section of the Er-Ni-In system at T=870 K was constructed by means of X-ray powder diffraction and EDX-analyses. Nine ternary compounds, namely ErNi{sub 9}In{sub 2} (YNi{sub 9}In{sub 2}-type), Er{sub 1-1.22}Ni{sub 4}In{sub 1-0.78} (MgCu{sub 4}Sn-type), Er{sub 10}Ni{sub 9.07}In{sub 20} (Ho{sub 10}Ni{sub 9}In{sub 20}-type), ErNi{sub 1-0.60}In{sub 1-1.40} (ZrNiAl-type), Er{sub 2}Ni{sub 2}In (Mn{sub 2}AlB{sub 2}-type), Er{sub 2}Ni{sub 1.78}In (Mo{sub 2}FeB{sub 2}-type), Er{sub 5}Ni{sub 2}In{sub 4} (Lu{sub 5}Ni{sub 2}In{sub 4}-type), Er{sub 5}Ni{sub 2}In (Mo{sub 5}SiB{sub 2}-type), and Er{sub 13.53}Ni{sub 3.14}In{sub 3.33} (Lu{sub 14}Co{sub 2}In{sub 3}-type), exist in the Er-Ni-In system at this temperature. The substitution of Ni for In was observed for ErNi{sub 1-0.60}In{sub 1-1.40} and In for Er in the case of related compounds ErNi{sub 2} and ErNi{sub 4}In. Er can enter NiIn (CoSn-type) leading to including-substitution type of compound Er{sub 0-0.12}NiIn{sub 1-0.89}. Basic magnetic properties of the Er{sub 0.04}NiIn{sub 0.97}, ErNi{sub 2}, Er{sub 0.9}Ni{sub 2}In{sub 0.1}, and ErNi{sub 4}In phases were inspected. Electrical-resistivity studies were performed on the ErNiIn, ErNi{sub 0.9}In{sub 1.1}, and ErNi{sub 4}In phases. - Graphical Abstract: Phase relations in the ternary system Er-Ni-In have been established for the isothermal section at T=870 K based on X-ray phase and EDX-analyses. Nine ternary compounds were observed. Highlights: > Isothermal section of Er-Ni-In system at T=870 K was constructed. > Nine ternary compounds were detected. > Basic magnetic properties of Er{sub 0.04}NiIn{sub 0.97} and ErNi{sub 4}In phases were inspected.

  12. 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

  13. 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.

  14. Bulk Er:YAP and Er:Yb:YAP optical emission studies for eyesafe laser applications

    NASA Astrophysics Data System (ADS)

    Georgiou, Efstratios; Boquillon, Jean-Pierre; Musset, Olivier

    2012-06-01

    Emission and excitation spectra of Er-doped YAP crystals reveal a broad emission band in the eyesafe region with peaks around 1545-nm and 1608-nm and pump-bands suitable for common 800-nm and 970-nm diode lasers, suggesting YAP as a candidate crystalline host for diode-pumped laser in the 1.5-μm eyesafe regime. Erbium-doped YAP-crystal results are comparable with analogous measurements on Er:Yb:YAG, which has already demostrated efficient lasing action in the eyesafe region.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Radiation Hydrodynamics with FLOW-ER

    NASA Astrophysics Data System (ADS)

    Marcello, Dominic; Tohline, J. E.; Motl, P. M.

    2008-03-01

    The effects of radiative transport are an important aspect of many astrophysical fluid problems, such as binary star accretion discs and common envelope evolution. Unfortunately, the full radiative transport problem is seven dimensional and outside the realm of current computational capabilities. The gray field flux limited diffusion (FLD) approximation has been shown to provide a feasible four dimensional approximation to the full radiative transport problems in many cases. The flux is approximated through an algebraic expression which interpolates between the two extremes of diffusive and free streaming radiation. FLD allows for the exchange of energy and momentum between the fluid and radiation field. We are implementing this into our current Newtonian astrophysical fluid simulation code named FLOW-ER. Unlike other FLD codes, FLOW-ER handles shocks without the use of artificial viscosity. At this point, the code runs in 1D and 2D on a single processor. The ultimate goal is a fully 3D parallel code running on an adaptive mesh. Presented are results for test cases in 1D and 2D, compared to analytic results where available, and to ZeusMP2 when not. This research has been supported, in part, by NSF grants AST-0407070 and AST-0708551.

  2. June 1997 ER-2 Flight Measurements

    NASA Technical Reports Server (NTRS)

    Jones, Irby W.

    2003-01-01

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

  3. ER Import Sites and Their Relationship to ER Exit Sites: A New Model for Bidirectional ER-Golgi Transport in Higher Plants.

    PubMed

    Lerich, Alexander; Hillmer, Stefan; Langhans, Markus; Scheuring, David; van Bentum, Paulien; Robinson, David G

    2012-01-01

    Per definition, ER exit sites are COPII vesiculation events at the surface of the ER and in higher plants are only visualizable in the electron microscope through cryofixation techniques. Fluorescent COPII labeling moves with Golgi stacks and locates to the interface between the ER and the Golgi. In contrast, the domain of the ER where retrograde COPI vesicles fuse, i.e., ER import sites (ERIS), has remained unclear. To identify ERIS we have employed ER-located SNAREs and tethering factors. We screened several SNAREs (SYP81, the SYP7 family, and USE1) to find a SNARE whose overexpression did not disrupt ER-Golgi traffic and which gave rise to discrete fluorescent punctae when expressed with an XFP tag. Only the Qc-SNARE SYP72 fulfilled these criteria. When coexpressed with SYP72-YFP, both the type I-membrane protein RFP-p24δ5 and the luminal marker CFP-HDEL whose ER localization are due to an efficient COPI-mediated recycling, form nodules along the tubular ER network. SYP72-YFP colocalizes with these nodules which are not seen when RFP-p24δ5 or CFP-HDEL is expressed alone or when SYP72-YFP is coexpressed with a mutant form of RFP-p24δ5 that cannot exit the ER. SYP72-YFP does not colocalize with Golgi markers, except when the Golgi stacks are immobilized through actin depolymerization. Endogenous SYP7 SNAREs, also colocalize with immobilized COPII/Golgi. In contrast, XFP-tagged versions of plant homologs to TIP20 of the Dsl1 COPI-tethering factor complex, and the COPII-tethering factor p115 colocalize perfectly with Golgi stacks irrespective of the motile status. These data suggest that COPI vesicle fusion with the ER is restricted to periods when Golgi stacks are stationary, but that when moving both COPII and COPI vesicles are tethered and collect in the ER-Golgi interface. Thus, the Golgi stack and an associated domain of the ER thereby constitute a mobile secretory and recycling unit: a unique feature in eukaryotic cells. PMID:22876251

  4. 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

  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. Untangling the web: Mechanisms underlying ER network formation

    PubMed Central

    Goyal, Uma; Blackstone, Craig

    2013-01-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

  7. 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.

  8. Technology for the ERS-1 SAR antenna

    NASA Astrophysics Data System (ADS)

    Wagner, R.

    1984-09-01

    The metallization of CFRP waveguides, the Deployable Truss Structure (DTS) and verification in terrestrial environment of the 10 x 1 m SAR antenna of ERS-1 (ESA satellite) are discussed. Waveguide metallization was achieved indirectly with metallization of the mandrel prior to CFRP lay-up, and directly, by electroplating of manufactured CFRP components. Both techniques proved unsatisfactory, but a surface treatment applied to the metal layer in the indirect technique improves adhesion strength by an order of magnitude, and enables the waveguides to meet requirements. The DTS satisfies launch, deployment, and inflight specifications for a 5 panel/2 wing structure. Ground tests include analytical simulation of deployment with and without gravity effects, and a gravity compensation technique for tests.

  9. 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.

  10. 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.

  11. 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

  12. 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 ...

  13. Erbium induced magnetic properties of Er/ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Jayachandraiah, C.; Sivakumar, K.; Divya, A.; Krishnaiah, G.

    2016-05-01

    Pure and Er (2, 3 and 4 at. %) doped ZnO nanoparticles have been synthesized by chemical co-precipitation method. EDS spectrum confirmed the presence of Zn, O and Er in the synthesized samples. The XRD measurements confirmed the hexagonal wurtzite structure of ZnO for all samples. The crystallite size of the samples decreases with increase in concentration and are compatible with the results that obtained from TEM analysis.EPR spectra exhibitedferromagnetic signals the substitution Er The possible ferromagnetic zinc interstials signal is appeared for 2 at. % of Er dopant. The room temperature ferromagnetic is observed only for 2 at. % of Er while all other samples exhibiting weak ferromagnetic nature.

  14. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  15. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  17. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  18. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. GRP78 Interacting Partner Bag5 Responds to ER Stress and Protects Cardiomyocytes From ER Stress-Induced Apoptosis.

    PubMed

    Gupta, Manish K; Tahrir, Farzaneh G; Knezevic, Tijana; White, Martyn K; Gordon, Jennifer; Cheung, Joseph Y; Khalili, Kamel; Feldman, Arthur M

    2016-08-01

    Bag5 is a member of the BAG family of molecular chaperone regulators and is unusual in that it consists of five BAG domains, which function as modulators of chaperone activity. Bag family proteins play a key role in cellular as well as in cardiac function and their differential expression is reported in heart failure. In this study, we examined the importance of a Bag family member protein, Bag5, in cardiomyocytes during endoplasmic reticulum (ER) stress. We found that expression of Bag5 in cardiomyocytes is significantly increased with the induction of ER stress in a time dependent manner. We have taken gain-in and loss-of functional approaches to characterize Bag5 protein function in cardiomyocytes. Adenoviral mediated expression of Bag5 significantly decreased cell death as well as improved cellular viability in ER stress. Along with this, ER stress-induced CHOP protein expression is significantly decreased in cells that overexpress Bag5. Conversely, we found that siRNA-mediated knockdown of Bag5 caused cell death, increased cytotoxicity, and decreased cellular viability in cardiomyocytes. Mechanistically, we found that Bag5 protein expression is significantly increased in the ER during ER stress and that this in turn modulates GRP78 protein stability and reduces ER stress. This study suggests that Bag5 is an important regulator of ER function and so could be exploited as a tool to improve cardiomyocyte function under stress conditions. J. Cell. Biochem. 117: 1813-1821, 2016. © 2016 Wiley Periodicals, Inc. PMID:26729625

  20. 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.

  1. Ultraviolet upconversion fluorescence of Er3+ in Yb3+/Er3+-codoped Gd2O3 nanotubes.

    PubMed

    Zheng, Kezhi; Zhao, Dan; Zhang, Daisheng; Liu, Zhenyu; Qin, Weiping

    2011-11-01

    Under 980 nm excitation, room-temperature ultraviolet (UV) upconversion (UC) emissions of Er3+ from the 4G(9/2), 2K(13/2), and 2P(3/2) states were observed in Gd2O3:Yb3+/Er3+ nanotubes, which were synthesized via a simple wet-chemical route at low temperature and ambient pressure followed by a subsequent heat treatment at 800 degrees C. The experimental results exhibited that these UV emissions came from four-photon UC processes. In the Gd2O3:Yb3+/Er3+ nanocrystals, the energy transfers (ETs) from Yb3+ to Er3+ played important roles in populating the high-energy states of Er3+ ions. This material provides a possible candidate for building UV compact solid-state lasers or fiber lasers. PMID:22413290

  2. In Vitro Study of Er:YAG and Er, Cr:YSGG Laser Irradiation on Human Gingival Fibroblast Cell Line.

    PubMed

    Talebi-Ardakani, Mohammad Reza; Torshabi, Maryam; Karami, Elahe; Arbabi, Elham; Rezaei Esfahrood, Zeinab

    2016-04-01

    The ultimate goal of the periodontal treatments is a regeneration of periodontium. Recently, laser irradiations are commonly used to improve wound repair. Because of many controversies about the effects of laser on soft tissue regeneration, more in vitro studies are still needed. The aim of the present in vitro study was to compare the effects of different doses of Er:YAG (erbium-doped:yttrium, aluminum, garnet) and Er, Cr:YSGG (erbium, chromium-doped: yttrium, scandium, gallium, garnet) laser treatment on human gingival fibroblasts (HGF) proliferation. In this randomized single-blind controlled in vitro trial, HGF cells were irradiated using Er:YAG and Er, Cr:YSGG laser for 10 and 30 seconds or remained unexposed as a control group. After a culture period of 24 and 48 hours, HGF cell proliferation was evaluated by MTT assay. The data were subjected to one-sided analysis of variance and Tukey multiple comparison tests. Our results showed Er:YAG application for 10 and 30 seconds as well as Er, Cr:YSGG irradiation for 10 and 30 seconds induced statistically significant (P<0.05) proliferation of HGF cells as compared with the control at 24 hours up to 18.39%, 26.22%, 21.21%, and 17.06% respectively. In 48 hour incubations, Er:YAG and Er, Cr:YSGG irradiation for 10 and 30 seconds significantly increased cellular proliferation up to 22.9%, 32.24%, 30.52% and 30.02% respectively (P<0.05). This study demonstrates that Er:YAG and Er, Cr:YSGG laser significantly increased HGF cell proliferation compared to the control specimens. This higher proliferation can lead to increased wound repair in clinical conditions. PMID:27309266

  3. Coupled ER to Golgi Transport Reconstituted with Purified Cytosolic Proteins

    PubMed Central

    Barlowe, Charles

    1997-01-01

    A cell-free vesicle fusion assay that reproduces a subreaction in transport of pro-α-factor from the ER to the Golgi complex has been used to fractionate yeast cytosol. Purified Sec18p, Uso1p, and LMA1 in the presence of ATP and GTP satisfies the requirement for cytosol in fusion of ER-derived vesicles with Golgi membranes. Although these purified factors are sufficient for vesicle docking and fusion, overall ER to Golgi transport in yeast semi-intact cells depends on COPII proteins (components of a membrane coat that drive vesicle budding from the ER). Thus, membrane fusion is coupled to vesicle formation in ER to Golgi transport even in the presence of saturating levels of purified fusion factors. Manipulation of the semi-intact cell assay is used to distinguish freely diffusible ER- derived vesicles containing pro-α-factor from docked vesicles and from fused vesicles. Uso1p mediates vesicle docking and produces a dilution resistant intermediate. Sec18p and LMA1 are not required for the docking phase, but are required for efficient fusion of ER- derived vesicles with the Golgi complex. Surprisingly, elevated levels of Sec23p complex (a subunit of the COPII coat) prevent vesicle fusion in a reversible manner, but do not interfere with vesicle docking. Ordering experiments using the dilution resistant intermediate and reversible Sec23p complex inhibition indicate Sec18p action is required before LMA1 function. PMID:9382859

  4. 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.

  5. 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.

  6. ER Stress-induced Aberrant Neuronal Maturation and Neurodevelopmental Disorders.

    PubMed

    Kawada, Koichi; Iekumo, Takaaki; Kaneko, Masayuki; Nomura, Yasuyuki; Okuma, Yasunobu

    2016-01-01

    Neurodevelopmental disorders, which include autism spectrum disorder, are congenital impairments in the growth and development of the central nervous system. They are mainly accentuated during infancy and childhood. Autism spectrum disorder may be caused by environmental factors, genomic imprinting of chromosome 15q11-q13 regions, and gene defects such as those in genes encoding neurexin and neuroligin, which are involved in synaptogenesis and synaptic signaling. However, regardless of the many reports on neurodevelopmental disorders, the pathogenic mechanism and treatment of neurodevelopmental disorders remain unclear. Conversely, it has been reported that endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases. ER stress is increased by environmental factors such as alcohol consumption and smoking. Here we show the recent results on ER stress-induced neurodevelopmental disorders. ER stress led to a decrease in the mRNA levels of the proneural factors Hes1/5 and Pax6, which maintain an undifferentiated state of the neural cells. This stress also led to a decrease in nestin expression and an increase in beta-III tubulin expression. In addition, dendrite length was shortened by ER stress in microtubule-associated protein-2 (MAP-2) positive cells. However, the ubiquitin ligase HRD1 expression was increased by ER stress. By suppressing HRD1 expression, the ER stress-induced decrease in nestin and MAP-2 expression and increase in beta-III tubulin returned to control levels. Therefore, we suggest that ER stress induces abnormalities in neuronal differentiation and maturation via HRD1 expression. These results suggest that targeting ER stress may facilitate quicker approaches toward the prevention and treatment of neurodevelopmental disorders. PMID:27252060

  7. 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

  8. 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.

  9. ER to synapse trafficking of NMDA receptors.

    PubMed

    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

  10. Large-scale ER-damper for seismic protection

    NASA Astrophysics Data System (ADS)

    McMahon, Scott; Makris, Nicos

    1997-05-01

    A large scale electrorheological (ER) damper has been designed, constructed, and tested. The damper consists of a main cylinder and a piston rod that pushes an ER-fluid through a number of stationary annular ducts. This damper is a scaled- up version of a prototype ER-damper which has been developed and extensively studied in the past. In this paper, results from comprehensive testing of the large-scale damper are presented, and the proposed theory developed for predicting the damper response is validated.

  11. 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

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

    NASA Technical Reports Server (NTRS)

    Anderson, Allen Joel; Sandwell, David T.

    1994-01-01

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

  13. Inhibitors of Protein Translocation Across the ER Membrane.

    PubMed

    Kalies, Kai-Uwe; Römisch, Karin

    2015-10-01

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

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

    SciTech Connect

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

    2014-05-21

    Er-concentration effect in GaAs;Er,O containing charge carriers (n-type, high resistance, p-type) has been studied by X-band Electron spin resonance (ESR) at low temperature (4.7 K < T < 18 K). Observed A, B, and C types of ESR signals were identical to those observed previously in GaAs:Er,O without carrier. The local structure around Er-2O centers is not affected by carriers because similar angular dependence of g-values was observed in both cases (with/without carrier). For temperature dependence, linewidth and lineshape analysis suggested the existence of Er dimers with antiferromagnetic exchange interaction of about 7 K. Moreover, drastic decrease of ESR intensity for C signal in p-type sample was observed and it correlates with the decrease of photoluminescence (PL) intensity. Possible model for the Er-2O trap level in GaAs:Er,O is discussed from the ESR and PL experimental results.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Properties of ER Fluids Comprised of Liquid Crystalline Polymers

    NASA Astrophysics Data System (ADS)

    Inoue, Akio; Ide, Yoichiroh; Maniwa, Shyunji; Yamada, Hiroyuki; Oda, Hiroji

    Side-chain liquid crystalline polysiloxanes (LCS) diluted with solvents show a large increase in viscosity and a newtonian flow under an electric field. Two types of solvent-diluted LCSs, A and B, are presented and their properties are described in this paper. Type A shows a large temperature-dependent ER effect a quick response of msec. order to an electric field and a dynamic behavior similar to that of a low molecular weight liquid crystal. Type B shows a stable ER effect throughout a wide range of temperatures up to 150°C, a two-step response of shear stress curve upon application of DC electric field and a micron-sized droplets structure which deforms with the electric field. The generation mechanisms of ER effect on the two types were discussed with the data of dynamic and morphological changes, referring those on a low molecular liquid crystal and a particle dispersion type ER fluid.

  20. Play 'Pokemon Go' without Landing in The ER

    MedlinePlus

    ... medlineplus.gov/news/fullstory_159911.html Play 'Pokemon Go' Without Landing in the ER Distracted walking a ... in pursuit of digital monsters via the "Pokemon Go" game. But players distracted by their smartphones risk ...

  1. ERS-1 and Almaz ocean wave monitoring experiments

    NASA Technical Reports Server (NTRS)

    Beal, R. C.; Tilley, D. G.

    1992-01-01

    Preliminary results from two ocean wave monitoring experiments conducted in 1991 using the high-altitude ERS-1 synthetic aperture radar (SAR) and the low-altitude ex-USSR Almaz 1 SAR are presented. ERS-1 imagery of the Gulf Stream supports the idea that a future wide-swath scansar will be a valuable tool for monitoring large-scale ocean dynamics at high resolution. A direct comparison of ERS-1 and Almaz 1 ocean wave spectra shows major deficiencies in the ERS-1 high range-to-velocity ratio R/V sensor that are partially resolved with the lower-altitude Almaz platform. Optimum wave imaging from space will require both a low R/V and low off-nadir angle.

  2. 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.

  3. 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

  4. Comparison of laser phacovaporization using the Er:YAG and the Er:YSGG laser

    NASA Astrophysics Data System (ADS)

    Gailitis, Raymond P.; Patterson, Scott W.; Samuels, Mark A.; Hagen, Kerry B.; Ren, Qiushi; Waring, George O., III

    1992-08-01

    Future advances in cataract surgery aim to remove the crystalline lens through a small opening such that the capsular bag, once devoid of lens epithelial cells, may be refilled with a clear polymer which may exhibit the elastic properties of a young lens and restore accommodation. Several different lasers are currently being investigated for laser cataract surgery including the excimer, pulsed visible and short infrared, and mid infrared lasers. Taking advantage of the strong water absorption peak at 2.94 micrometers , we have investigated the laser tissue interaction of the Er:YAG (2.94 micrometers ) and Er:YSGG (2.79 micrometers ) which have water absorption coefficients of 13,000 cm-1 and 7,000 cm-1, respectively. We have devised a delivery system which measures the ablation time versus radiant energy through a known thickness on a lens nucleus in free air for these two wavelengths. The current presentation compares the ablation rates versus radiant exposure of these two lasers in human lens nuclei. We also show the histopathology from ablated lenses of these two different wavelengths at different radiant exposures. Integration with fiberoptics and clinical applications is discussed.

  5. 5 d-4 f luminescence of Er 3+ in YAG:Er 3+

    NASA Astrophysics Data System (ADS)

    Aleksanyan, Eduard; Harutunyan, Vachagan; Kostanyan, Radik; Feldbach, Eduard; Kirm, Marco; Liblik, Peeter; Makhov, Vladimir N.; Vielhauer, Sebastian

    2009-04-01

    Interconfigurational 4 f105 d ↔ 4 f11 transitions of the Er 3+ ion in the YAG host were studied under both VUV photon (synchrotron radiation) and electron beam excitation. It was found that the lowest low-spin 5 d level of the Er 3+ ion has a rather large energy gap to the next lower 4 f2D(2) 5/2 crystal-field level, which results in a relatively low rate of nonradiative transitions from this 5 d level leading to the appearance of weak spin-allowed 5 d-4 f luminescence at low temperature. The lowest high-spin 5 d level, from which spin-forbidden 5 d-4 f radiative transitions could occur potentially, is situated only at ˜500 cm -1 above the 4D1/2 level. Such close location allows fast depopulation of the 5 d level resulting in the absence of spin-forbidden 5 d-4 f luminescence and appearance of 4D1/2 4 f-4 f luminescence.

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

    PubMed

    Greig, Sarah L

    2015-11-01

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Oceanographic results from analysis of ERS-1 altimetry

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  14. 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.

  15. 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.

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

    PubMed Central

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

    2014-01-01

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

  17. 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.

  18. Activation cross sections of proton and deuteron induced nuclear reactions on holmium and erbium, related to the production of (161)Er and (160)Er medical isotopes.

    PubMed

    Tárkányi, F; Ditrói, F; Takács, S; Hermanne, A; Baba, M

    2016-09-01

    Experimental excitation functions for long-lived products in proton induced reactions were measured with the activation method in the 37-65MeV energy range on natural holmium. Stacked foil irradiation technique and high resolution gamma spectrometry were used in order to measure cross-section data for the production of (161)Er, (160)Er and (1)(59,157)Dy. For comparison of the production routes of medically related (161)Er and (160)Er radioisotopes new experimental cross section data were deduced for the (162)Er(p,x)(161,160)Er and (162)Er(d,x)(161,160)Er reactions by re-evaluating gamma-ray spectra from earlier measurements. No earlier data were found in the literature for these reactions. The experimental data are compared with results of TALYS theoretical code reported in TENDL-2015. PMID:27451109

  19. 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

  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

  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. Mechanisms determining the morphology of the peripheral ER.

    PubMed

    Shibata, Yoko; Shemesh, Tom; Prinz, William A; Palazzo, Alexander F; Kozlov, Michael M; Rapoport, Tom A

    2010-11-24

    The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by the curvature-stabilizing proteins reticulons and DP1/Yop1p, but how the sheets are formed is unclear. Here, we identify several sheet-enriched membrane proteins in the mammalian ER, including proteins that translocate and modify newly synthesized polypeptides, as well as coiled-coil membrane proteins that are highly upregulated in cells with proliferated ER sheets, all of which are localized by membrane-bound polysomes. These results indicate that sheets and tubules correspond to rough and smooth ER, respectively. One of the coiled-coil proteins, Climp63, serves as a "luminal ER spacer" and forms sheets when overexpressed. More universally, however, sheet formation appears to involve the reticulons and DP1/Yop1p, which localize to sheet edges and whose abundance determines the ratio of sheets to tubules. These proteins may generate sheets by stabilizing the high curvature of edges. PMID:21111237

  3. 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.

  4. 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.

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

    PubMed

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

    2015-01-01

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

  6. 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 β-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.

  7. 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

  8. Er:YAG laser metal and ceramic bracket debonding

    NASA Astrophysics Data System (ADS)

    Dostálová, Tat'jana; Remeš, Marek; Jelínková, Helena; Å ulc, Jan; Němec, Michal; Vyhlídal, David

    2016-02-01

    The goal of the study was investigation of Er:YAG radiation (wavelength 2.94 μm) interaction with various metal and ceramic brackets and adhesive materials. The source of radiation was a free-running Er: YAG laser generating pulses with energy 280 mJ, 250 μs long and repetition rate 6 Hz (mean power 1.7 W). During the treatment lasting 140 s, water cooling was implemented and only the brackets were irradiated. It has been observed that the brackets were removed easily after the Er:YAG laser irradiation, and temperature rise was limited also for metal brackets. SEM investigation has confirmed less damage of enamel in comparison with non-irradiated samples.

  9. 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.

  10. ER Protein Processing Under Oxidative Stress: Implications and Prevention.

    PubMed

    Khalil, Mahmoud F; Valenzuela, Carlos; Sisniega, Daniella; Skouta, Rachid; Narayan, Mahesh

    2016-06-01

    Elevated levels of mitochondrial nitrosative stress have been associated with the pathogenesis of both Parkinson's and Alzheimer's diseases. The mechanism involves catalytic poisoning of the endoplasmic reticulum (ER)-resident oxidoreductase chaperone, protein disulfide isomerase (PDI), and the subsequent accumulation of ER-processed substrate proteins. Using a model system to mimic mitochondrial oxidative and nitrosative stress, we demonstrate a PDI-independent mechanism whereby reactive oxygen species (ROS) compromise regeneration rates of disulfide bond-containing ER-processed proteins. Under ROS-duress, the secretion-destined traffic adopts disulfide-exposed structures making the protein flux retrotranslocation biased. We also demonstrate that ROS-compromised protein maturation rates can be rescued by the polyphenol ellagic acid (EA). Our results are significant in that they reveal an additional mechanism which could promote neurodegenerative disorders. Furthermore, our data reveal that EA possesses therapeutic potential as a lead prophylactic agent against oxidative/nitrosative stress-related neurodegenerative diseases. PMID:26983927

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

    PubMed Central

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

    2016-01-01

    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 Ca2+-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. 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.

  13. On the accuracy of ERS-1 orbit predictions

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2005-02-01

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

  16. 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

  17. Next generation Er:YAG fractional ablative laser

    NASA Astrophysics Data System (ADS)

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

  18. Integral field spectroscopy of SN 2002er with PMAS

    NASA Astrophysics Data System (ADS)

    Christensen, L.; Becker, T.; Jahnke, K.; Kelz, A.; Roth, M. M.; Sánchez, S. F.; Wisotzki, L.

    2003-04-01

    We present observations of the Type Ia supernova SN 2002er during the brightening phase. The observations were performed with the Potsdam Multi Aperture Spectrophotometer (PMAS) integral field instrument. Due to the 8arcsecx8 arcsec field of view of the spectrograph an accurate background subtraction was possible. Results from analyses of the evolution of absorption features in comparisons with other SNe show that SN 2002er is a fairly bright Type Ia supernova with a peak brightness of MB=-19.6+/-0.1.

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    Spangler, Lee H.

    1994-12-01

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

  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. ERS-1 scatterometer measurements over the Southern Ocean

    NASA Technical Reports Server (NTRS)

    Freilich, M. H.

    1994-01-01

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

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

    NASA Technical Reports Server (NTRS)

    1998-01-01

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

  4. Thermal effects in Er:strengthened-glass laser

    NASA Astrophysics Data System (ADS)

    Tilleman, Michael M.; Jackel, Steven M.; Moshe, Inon

    1998-06-01

    We report the development of a high-power Er:strengthened- glass laser emitting at the eye-safe 1.535 μm wavelength. The flashlamp pumped Cr:Yb:Er:glass produced 330 mJ output @ 0.45% slope efficiency. Thermo-optical measurements indicated strong thermal lensing, of 16 diopter/kW and mild birefringence induced depolarization of 5% at 200 W. In terms of radial and birefringence elastooptical coefficients these data determine the values of 0.075 +/- 0.002 and 0.0094, respectively. For a hemispherical resonator configuration a TEM00 beam was achieved.

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

    NASA Technical Reports Server (NTRS)

    Hans, P.; Schuessler, H.

    1984-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Spangler, Lee H.

    1994-01-01

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

  7. 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

  8. Inelastic-neutron-scattering study of the Er3+ energy levels in ErBa2Cu3O7

    NASA Astrophysics Data System (ADS)

    Soderholm, L.; Loong, C.-K.; Kern, S.

    1992-05-01

    Magnetic excitation spectra of ErBa2Cu3O7 have been measured by use of inelastic neutron scattering. Optimal experimental conditions allow the resolution of the transitions between the Er3+ ground state and all seven excited states within the 4I15/2 Russell-Saunders ground multiplet. The data are analyzed in terms of an intermediate-coupling crystal-field model, calculated using spherical-tensor techniques. Calculated spectra based on the results of this analysis are consistent with all experimental spectra, including those obtained at higher temperatures. The eigenfunctions and eigenvalues obtained from this analysis are used to calculate the magnetic properties expected of Er3+ in this crystal environment.

  9. 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

  10. ER-α36, a novel isoform of ER-α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast

    PubMed Central

    Vranic, Semir; Gatalica, Zoran; Deng, Hao; Frkovic-Grazio, Snjezana; Lee, Lisa M J; Gurjeva, Olga; Wang, Zhao-Yi

    2012-01-01

    Background ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways. Aim To examine the expression of ER-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 negative and currently lack effective targeted therapeutic options. Methods 19 pure apocrine carcinomas (17 invasive and two in-situ carcinomas) and 11 adenoid cystic carcinomas of the breast were evaluated for ER-α36 expression, along with expressions of ER-α66, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods. Results All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-α66 and PR negative, AR strongly positive). ER-α36 expression was detected in 18/19 pure apocrine carcinomas (94.7%, 95% CI 75.1 to 98.7) in predominantly membranous and cytoplasmic distribution. When positive, pure apocrine carcinomas uniformly (100% of cells) expressed ER-α36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-α36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar sub-cellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-α36 in the majority of cells (average 76%). Conclusion ER-α36, a novel isoform of ER-α66, is frequently over-expressed in apocrine and adenoid cystic carcinomas of the breast. These results indicate a potential for a novel targeted treatment in these cancers. PMID:21045236

  11. 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.

  12. Determination of the Er3+ to Yb3+ energy transfer efficiency in Er3+/Yb3+-codoped YVO4 crystals

    NASA Astrophysics Data System (ADS)

    Di Paolo, R. E.; Cantelar, E.; Wang, X. M.; Tsuboi, T.; Cussó, F.

    2001-09-01

    The energy transfer efficiency from Er3+ to Yb3+ ions in yttrium orthovanadate single crystals (YVO4) is experimentally obtained, by using a method based on the simultaneous and multiwavelength measurement of photoacoustic and luminescent signals after pulsed laser excitation. The result is reached by comparing with the predictions from Judd-Ofelt analysis and the lifetime measurements. The energy transfer between the ions, from Er3+ to Yb3+, must be considered in order to fit the experimental results. A value of energy transfer efficiency (Ψ = 0.16) is obtained.

  13. Optical transitions of Er3+ ions in fluorozirconate glass

    NASA Astrophysics Data System (ADS)

    Shinn, M. D.; Sibley, W. A.; Drexhage, M. G.; Brown, R. N.

    1983-06-01

    Optical-absorption, -emission, and -excitation spectra are presented for Er3+ ions in fluorozirconate glass. Measured oscillator strengths of the transitions between J manifolds at 300 and 15 K are compared with calculated electric and magnetic dipole oscillator strengths. Radiative rates for five luminescing states were calculated. The nonradiative rates from these excited states were determined by calculating the difference between the measured rates and the calculated radiative rates. The low-temperature nonradiative rates are in agreement with the phenomenological energy-gap law followed by rare-earth ions in a number of crystals and glasses. The temperature dependence of the lifetimes was analyzed using the Huang-Rhys theory of multiphonon emission. Values for the 4I112 radiative and nonradiative rates obtained by the above methods are compared with those obtained applying the method Flaherty and DiBartolo used to study MnF2: Er3+. The multiphonon emission rates in fluorozirconate glass are much lower than the rates for the same levels of Er3+ in oxide glasses. Measurements of the bandwidths of the ground and excited states of Er3+ and the nearly exponential decay of the emissions indicate a relatively narrow distribution of site symmetries compared to oxide glasses.

  14. 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.

  15. Calcium and ER stress mediate hepatic apoptosis after burn injury

    PubMed Central

    Gauglitz, Gerd G.; Song, Juquan; Kulp, Gabriela A.; Finnerty, Celeste C.; Cox, Robert A.; Barral, José M.; Herndon, David N.; Boehning, Darren

    2009-01-01

    Abstract A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time‐points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn‐induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function – effects which may be mediated by increased calcium release by inositol 1,4,5‐trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury. PMID:20141609

  16. Staff Survey Results, 2000-2001. E&R Report.

    ERIC Educational Resources Information Center

    Wildman, Wanda N.

    Evaluation and Research (E&R) staff of the Wake County Public Schools (WCPSS), North Carolina, have conducted spring surveys of school staff since 1992. This report contains information from the survey distributed in March 2001. Completed surveys were returned by 5,755 staff members. Survey results indicate that in the year 2000, more staff…

  17. 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…

  18. 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…

  19. 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

  20. Historisches Rätsel Er hatte den Durchblick

    NASA Astrophysics Data System (ADS)

    Loos, Andreas

    2002-03-01

    Seine Jugend ist voller Schicksalsschläge: Mit zwölf Jahren wird er als elftes und jüngstes Kind eines Glasermeisters Vollwaise, mit vierzehn stürzt das Haus seines Pflegevaters und Lehrherren über ihm zusammen. Auch ist ihm kein langes Leben vergönnt: Mit gerade 39 Jahren ereilt ihn die Lungen- und Nervenschwindsucht.

  1. Spectroscopic properties of Nd, Er codoped glasses for solar pumped fiber lasers

    NASA Astrophysics Data System (ADS)

    Mizuno, Shintaro; Ito, Hiroshi; Hasegawa, Kazuo; Kawai, Hiroyuki; Nasu, Hiroyuki; Hughes, Mark A.; Suzuki, Takenobu; Ohishi, Yasutake

    2011-03-01

    The absorption and fluorescence characteristics of Er doped and Nd, Er codoped fluoride glasses were investigated under illumination of the simulated sunlight, laser or a monochromatic light filtered from a Xe lamp. Er was used as a sensitizing agent enhancing the energy conversion and the emission efficiency of Nd ions in fluoride glass intended for the sunlight excitation. Er doped fluoride glasses showed four emission peaks under simulated sunlight illumination at the wavelengths of 550, 848, 980, and 1530 nm attributed to the electronic transitions of Er3+ ions. The quantum efficiency of the emission from all of the bands had a peak at x = 0.5 mol. % Er and with the maximum of 73 %. The intensity of each emission band showed different ratios for various ErF3 contents. It is expected that concentration quenching of 4S3/2 state is easy to occur with high concentration of ErF3 compared to the other states. The energy transfer from Er to Nd was studied using a monochromatic light illumination which is absorbed by Er3+ ions only. Strong contribution of Er absorption to the 1.05 μm emission of Nd, Er co-doped fluoride glass was observed. Er was confirmed as a suitable sensitizer for the enhanced energy conversion and emission efficiency of Nd ions in ZBLAN glasses which are proposed for highly efficient solar pumped fiber lasers.

  2. 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

  3. Precise satellite orbit determination with particular application to ERS-1

    NASA Astrophysics Data System (ADS)

    Fernandes, Maria Joana Afonso Pereira

    The motivation behind this study is twofold. First to assess the accuracy of ERS-1 long arc ephemerides using state of the art models. Second, to develop improved methods for determining precise ERS-1 orbits using either short or long arc techniques. The SATAN programs, for the computation of satellite orbits using laser data were used. Several facilities were added to the original programs: the processing of PRARE range and altimeter data, and a number of algorithms that allow more flexible solutions by adjusting a number of additional parameters. The first part of this study, before the launch of ERS-1, was done with SEAS AT data. The accuracy of SEASAT orbits computed with PRARE simulated data has been determined. The effect of temporal distribution of tracking data along the arc and the extent to which altimetry can replace range data have been investigated. The second part starts with the computation of ERS-1 long arc solutions using laser data. Some aspects of modelling the two main forces affecting ERS-l's orbit are investigated. With regard to the gravitational forces, the adjustment of a set of geopotential coefficients has been considered. With respect to atmospheric drag, extensive research has been carried out on determining the influence on orbit accuracy of the measurements of solar fluxes (P10.7 indices) and geomagnetic activity (Kp indices) used by the atmospheric model in the computation of atmospheric density at satellite height. Two new short arc methods have been developed: the Constrained and the Bayesian method. Both methods are dynamic and consist of solving for the 6 osculating elements. Using different techniques, both methods overcome the problem of normal matrix ill- conditioning by constraining the solution. The accuracy and applicability of these methods are discussed and compared with the traditional non-dynamic TAR method.

  4. Systemic effects of AGEs in ER stress induction in vivo.

    PubMed

    Adamopoulos, Christos; Mihailidou, Chrysovalantou; Grivaki, Christofora; Papavassiliou, Kostas A; Kiaris, Hippokratis; Piperi, Christina; Papavassiliou, Athanasios G

    2016-08-01

    Emerging evidence indicates that accumulation of advanced glycation end products (AGEs) in human tissues may contribute to cell injury, inflammation and apoptosis through induction of endoplasmic reticulum (ER) stress. Human metabolism relies on ER homeostasis for the coordinated response of all metabolic organs by controlling the synthesis and catabolism of various nutrients. In vitro studies have demonstrated AGE-induced enhancement of unfolded protein response (UPR) in different cell types including endothelial, neuronal, pancreatic cells and podocytes, suggesting this crosstalk as an underlying pathological mechanism that contributes to metabolic diseases. In this minireview, we describe in vivo studies undertaken by our group and others that demonstrate the diverse systemic effects of AGEs in ER stress induction in major metabolic tissues such as brain, kidney, liver and pancreas of normal mice. Administration of high-AGEs content diet to normal mice for the period of 4 weeks upergulates the mRNA and protein levels of ER chaperone Bip (GRP78) indicative of UPR initiation in all major metabolic organs and induces activation of the pivotal transcription factor XBP1 that regulates glucose and lipid metabolism. Furthermore, animals with genetic ablation of UPR-activated transcription factor C/EBP homologous protein CHOP allocated in high-AGEs diet, exhibited relative resistance to UPR induction (BiP levels) and XBP1 activation in major metabolic organs. Since CHOP presents a critical mediator that links accumulation and aggregation of unfolded proteins with induction of oxidative stress and ER stress-related apoptosis, it is revealed as an important molecular target for the management of metabolic diseases. PMID:27236787

  5. Soluble tyrosinase is an endoplasmic reticulum (ER)-associated degradation substrate retained in the ER by calreticulin and BiP/GRP78 and not calnexin.

    PubMed

    Popescu, Costin I; Paduraru, Crina; Dwek, Raymond A; Petrescu, Stefana M

    2005-04-01

    Tyrosinase is a type I membrane protein regulating the pigmentation process in humans. Mutations of the human tyrosinase gene cause the tyrosinase negative type I oculocutaneous albinism (OCAI). Some OCAI mutations were shown to delete the transmembrane domain or to affect its hydrophobic properties, resulting in soluble tyrosinase mutants that are retained in the endoplasmic reticulum (ER). To understand the specific mechanisms involved in the ER retention of soluble tyrosinase, we have constructed a tyrosinase mutant truncated at its C-terminal end and investigated its maturation process. The mutant is retained in the ER, and it is degraded through the proteasomal pathway. We determined that the mannose trimming is required for an efficient degradation process. Moreover, this soluble ER-associated degradation substrate is stopped at the ER quality control checkpoint with no requirements for an ER-Golgi recycling pathway. Co-immmunoprecipitation experiments showed that soluble tyrosinase interacts with calreticulin and BiP/GRP78 (and not calnexin) during its ER transit. Expression of soluble tyrosinase in calreticulin-deficient cells resulted in the export of soluble tyrosinase of the ER, indicating the calreticulin role in ER retention. Taken together, these data show that OCAI soluble tyrosinase is an ER-associated degradation substrate that, unlike other albino tyrosinases, associates with calreticulin and BiP/GRP78. The lack of specificity for calnexin interaction reveals a novel role for calreticulin in OCAI albinism. PMID:15677452

  6. 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.

  7. SEAP activity serves for demonstrating ER stress induction by glucolipotoxicity as well as testing ER stress inhibitory potential of therapeutic agents.

    PubMed

    Lenin, Raji; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-06-01

    Endoplasmic reticulum (ER) stress is emerging as a unifying paradigm and one of the underlying mechanisms in the genesis of diabetes and its complications. While this has prompted the development of ER stress inhibitors, there is a limitation in monitoring of ER stress in vitro and in vivo by reliable methodologies. We validated the secreted alkaline phosphatase (SEAP) activity as a surrogate marker of ER stress in mouse β-TC6 cells exposed to glucolipotoxicity or tunicamycin and studied insulin secretion along with alterations in ER stress markers. SEAP activity assay was measured using the Great EscAPe SEAP kit, insulin levels were determined by Mercodia reagents and mRNA expression of ER stress markers was quantified by real-time PCR. SEAP activity in β-cells was significantly decreased (indicating increased ER stress) on exposure either to glucolipotoxicity or tunicamycin. This was accompanied by an increased mRNA expression of ER stress markers (GRP-78, PERK, IRE1α, ATF6, XBP-1, and CHOP) and decreased insulin secretion. Treating the cells with phenylbutyric acid normalized SEAP activity, decreased mRNA expression of ER stress markers and improved insulin secretion. Interestingly, cells exposed to different classes of anti-diabetes agents or compounds such as resveratrol resisted ER stress. Methylglyoxal also induces ER stress and this was counteracted by aminoguanidine. Out study demonstrates SEAP activity as a novel ER stress monitoring assay to investigate the therapeutic value of agents with ER stress inhibitory potential. Future studies should focus on the exercise of adopting this reporter assay for high-throughput screening mode of drug discovery. PMID:25776571

  8. NASA ER-2: Flying Laboratory for Earth Science Studies and Remote Sensing

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    This viewgraph presentation shows views of the ER-2, NASA's Flying Laboratory for Earth Science Studies and Remote Sensing. The presentation briefly reviews the successes of the ER-2, and what the facility provides.

  9. 78 FR 40484 - Determination That METADATE ER (Methylphenidate Hydrochloride) Extended-Release Tablet, 10...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-05

    ... HUMAN SERVICES Food and Drug Administration Determination That METADATE ER (Methylphenidate... Administration (FDA) has determined that METADATE ER (methylphenidate hydrochloride (HCl)) extended-release... determination will allow FDA to approve abbreviated new drug applications (ANDAs) for methylphenidate...

  10. Measuring Trends in Salaries and Wages in Public Schools: ERS Composite Indicator of Changes. ERS Information Aid.

    ERIC Educational Resources Information Center

    Educational Research Service, Arlington, VA.

    The composite indicator, published annually by the Educational Research Service (ERS), was designed to reflect overall changes in average salaries and wages paid by public school systems. The purpose of this book is to describe the nature of the indicator, how it is compiled on a national and state basis, and how local school systems can compile…

  11. Site symmetry of Er3+ in In0.5Ga0.5P

    NASA Astrophysics Data System (ADS)

    Jeong, B. S.; Hong, Y. K.; An, J. Y.; Choi, J. C.; Chung, C. H.; Park, H. L.

    1995-01-01

    The site and site symmetry of Er3+ in LPE grown In0.5Ga0.5P have been investigated for the first time through Raman and polarized luminescence spectroscopic techniques. The Er3+ site was found to be ErIn in In0.5Ga0.5P. The site symmetry of Er3+ in In0.5Ga0.5P was positively confirmed asC2v.

  12. 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

  13. ER-Mitochondria contact sites: A new regulator of cellular calcium flux comes into play.

    PubMed

    Krols, Michiel; Bultynck, Geert; Janssens, Sophie

    2016-08-15

    Endoplasmic reticulum (ER)-mitochondria membrane contacts are hotspots for calcium signaling. In this issue, Raturi et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201512077) show that the thioredoxin TMX1 inhibits the calcium pump SERCA2b at ER-mitochondria contact sites, thereby affecting ER-mitochondrial calcium transfer and mitochondrial bioenergetics. PMID:27528654

  14. Return to sender: use of Plasmodium ER retrieval sequences to study protein transport in the infected erythrocyte and predict putative ER protein families.

    PubMed

    Külzer, Simone; Gehde, Nina; Przyborski, Jude M

    2009-06-01

    We have investigated how knowledge of endoplasmic reticulum (ER) retrieval signals can be used to study specific trafficking pathways in the malaria-infected erythrocyte. We show that addition of various lumenal ER retrieval signals to soluble green fluorescent protein (GFP) chimaera causes retrieval of the fusion protein in the parasite's ER. In contrast, adding these signals to the C-terminus of a membrane bound protein does not affect its eventual sub-cellular localization. This demonstrates proof of principle that ER retrieval signals can be used to study the solubility state of Plasmodium falciparum proteins during their transport to the host erythrocyte. Furthermore, using our knowledge of ER retrieval signals, we identify Plasmodium ER protein families and assign putative functions to them. PMID:19294420

  15. Involvement of ER stress in retinal cell death

    PubMed Central

    Shimazawa, Masamitsu; Inokuchi, Yuta; Ito, Yasushi; Murata, Hiroshi; Aihara, Makoto; Miura, Masayuki; Araie, Makoto

    2007-01-01

    Purpose To clarify whether endoplasmic reticulum (ER) stress is involved in retinal cell death, using cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed with E1A virus), and transgenic mice ER stress-activated indicator (ERAI) mice carrying a human XBP1 and venus a variant of green fluorescent protein (GFP) fusion gene. Methods RGC-5 damage was induced by tunicamycin, and cell viability was measured by double nuclear staining (Hoechst 33342 and either YO-PRO-1 or propidium iodide). The expressions of glucose-regulated protein 78(GRP78)/BiP, the phosphorylated form of eukaryotic initiation factor 2α (p-eIF2α), and C/EBP-homologous (CHOP) protein after tunicamycin (in vitro or in vivo) or N-methyl-D-aspartate (NMDA; in vivo) treatment were measured using immunoblot or immunostaining. ERAI mice carrying the F-XBP1-DBD-venus expression gene were used to monitor ER-stress in vivo. Twenty-four hours after intravitreal injection of tunicamycin or NMDA, or after raising intraocular pressure (IOP), the retinal fluorescence intensity was visualized in anesthetized animals using an ophthalmoscope and in retinal flatmount or cross-section specimens using laser confocal microscopy. Results Treatment with tunicamycin induced apoptotic cell death in RGC-5 and also induced production of ER stress-related proteins (BiP, the phosphorylated form of eIF2α, and CHOP protein). In vivo, tunicamycin induced retinal ganglion cell (RGC) loss and thinning of the inner plexiform layer, 7 days after intravitreal injection. In flatmounted retinas of ERAI mice, the fluorescence intensity arising from the XBP-1-venus fusion protein, indicating ER-stress activation, was increased at 24 h after tunicamycin, NMDA, or IOP elevation. In transverse cross-sections from ERAI mice, the fluorescence intensity was first increased in cells of the ganglion cell and inner plexiform layers at 12 and 24 h, respectively, after NMDA injection, and it was localized to ganglion and

  16. Er and Yb isotope fractionation in planetary materials

    NASA Astrophysics Data System (ADS)

    Albalat, Emmanuelle; Telouk, Philippe; Albarède, Francis

    2012-11-01

    Terrestrial planets are depleted in volatile elements relative to solar abundances. Little is known, however, about volatility at the high temperatures relevant to asteroidal collisions and to the giant lunar impact. Although refractory rare-earth elements have overall similar crystallochemical properties, some differ in their temperatures of condensation from the nebular gas. This is the case for Yb, which condenses at ˜1490K and in the vapor is mostly in elemental form. By contrast, Er, largely present as ErO, condenses at ˜1660K. We analyzed the Er and Yb isotopic compositions in 33 terrestrial basalts, garnets, different classes of chondrites and achondrites, and lunar samples by MC-ICP-MS. The range of mass-dependent isotope fractionation is larger for Yb (0.43‰ per amu) than Er (0.23‰) isotopes. For terrestrial rocks, a positive correlation between δYb and La/Yb suggests that the isotopic differences between Er and Yb can be accounted for by the presence of small fractions of Yb2+. Yb is isotopically heavy in kimberlite and light in garnets. Ytterbium behaves similarly to Fe, with Yb3+ being more incompatible than the much less abundant Yb2+. In addition, the coexistence of divalent and trivalent sites in the garnet structure and the preference of heavy isotopes for stable bonds makes Yb in garnet isotopically light. The deficit of heavy Yb isotopes in lunar basaltic samples relative to the Earth, chondrites, and eucrites provides new evidence that the Moon formed by the condensation of silicate vapor in the aftermath of the giant lunar impact. Separation of vapor from melt and of heavy from light isotopes is first expected during the adiabatic expansion of the initial vapor plume. Subsequently, friction between melt and gas tends to further enrich the Moon feeding zone in silicate vapor to compensate the inward migration of melt out of the pre-lunar disk. A major consequence of interpreting the present lunar data by vapor/melt segregation is that the

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2014-05-21

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

  20. 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

  1. Multiple magnetic transitions in Er2Ni2Pb

    NASA Astrophysics Data System (ADS)

    Chinchure, Aravind D.; Muñoz-Sandoval, E.; Mydosh, J. A.

    2001-07-01

    We have fabricated single-phase samples and measured the bulk properties for one (Er) of a series of ternary, heavy rare-earth, 221 ``plumbide'' intermetallic compounds R2Ni2Pb (R=rare earths). These materials form in the orthorhombic (space group Cmmm) structure which is isostructural to Mn2AlB2 compounds. Our results of susceptibility, magnetization, heat capacity, and (magneto) resistivity on Er2Ni2Pb show (sharp) multiple antiferromagnetic transitions and strong field dependences in all bulk properties for the temperature range 2-10 K. We relate this magnetic behavior to the unusual R symmetry (partially frustrated) of the highly anisotropic plumbide crystal structure.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  4. 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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  6. Thermal lensing and stress in Cr,Er:YSGG

    NASA Astrophysics Data System (ADS)

    Gollihar, William A.; Margo, Satrijo T.; DeShazer, Larry G.; Kennedy, Chandler J.

    1995-04-01

    Thermal and stress lensing effects have been measured in a Cr,Er:YSGG rod by observing a transmitted 1064 nm Nd:YAG beam diverging from an operating Cr,Er:YSGG laser. The results compare favorably with theory and estimated thermal-optic properties of YSGG, which is intermediate between YAG and GSGG. Numerical simulations of the laser agree substantially with the threshold and power observed and show a heat generation rate which is consistent with our observations of lensing. Thermal fracture of the rod has been observed on several occasions, leading to an estimate of the thermal fracture figure of merit which is also intermediate between YAG and GSGG. Back focal distances of less than 20 cm occur in the vicinity of half the thermal rupture limit.

  7. 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.

  8. Tunable eye-safe Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Němec, M.; Šulc, J.; Indra, L.; Fibrich, M.; Jelínková, 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.

  9. 100-megawatt power Q-switched Er-glass laser

    NASA Astrophysics Data System (ADS)

    Taboada, John; Taboada, John M.; Stolarski, David J.; Zohner, Justin J.; Chavey, Lucas J.; Hodnett, Harvey M.; Noojin, Gary D.; Thomas, Robert J.; Kumru, Semih S.; Cain, Clarence P.

    2006-02-01

    A very high energy Q-switched Er-glass laser is reported. We incorporated a rotating, resonant mirror/Porro-cavity reflector optical arrangement to achieve very high shutter speeds on the cavity Q of a laser designed for energetic, flashlamp-pumped, 600-μs, 1540-nm pulses. Reproducible 3.75-J, 35-ns, 1533-nm laser pulses were obtained at a repetition rate less than 1 minute. Our work shows that reliable, very high energy, Q-switched, Er-glass laser pulses at 1533 nm can be generated mechanically with no apparent damage to laser cavity components. We demonstrate the applications of this "eye safe" wavelength to energetic processes such as LIBS and materials processing. The laser could also serve as a new tool for bioeffects studies and targeting applications.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  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. ER-stress in Alzheimer's disease: turning the scale?

    PubMed

    Endres, Kristina; Reinhardt, Sven

    2013-01-01

    Pathogenic mechanisms of Alzheimer's disease (AD) are intensely investigated as it is the most common form of dementia and burdens society by its costs and social demands. While key molecules such as A-beta peptides and tau have been identified decades ago, it is still enigmatic what drives the disease in its sporadic manifestation. Synthesis of A-beta peptides as well as phosphorylation of tau proteins comprise normal cellular functions and occur in principle in the healthy as well as in dementia-affected persons. Dyshomeostasis of Amyloid Precursor Protein (APP) cleavage, energy metabolism or kinase/phosphatase activity due to stressors has been suggested as a trigger of the disease. One way for cells to escape stress based on dysfunction of ER is the unfolded protein response - the UPR. This pathway is composed out of three different routes that differ in proteins involved, targets and consequences for cell fate: activation of transmembrane ER resident kinases IRE1-alpha and PERK or monomerization of membrane-anchored activating transcription factor 6 (ATF6) induce activation of versatile transcription factors (XBP-1, eIF2-alpha/ATF4 and ATF6 P50). These bind to specific DNA sequences on target gene promoters and on one hand attenuate general ER-prone protein synthesis and on the other equip the cell with tools to de-stress. If cells fail in stress compensation, this signaling also is able to evoke apoptosis. In this review we summarized knowledge on how APP processing and phosphorylation of tau might be influenced by ER-stress signaling. In addition, we depicted the effects UPR itself seems to have on molecules closely related to AD and describe what is known about UPR in AD animal models as well as in human patients. PMID:24319643

  13. 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.

  14. 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.

  15. 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

  16. Root canal preparation with Er:YSGG laser

    NASA Astrophysics Data System (ADS)

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

    1994-12-01

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

  17. Electron paramagnetic resonance of Er3+ ions in aluminum nitride

    NASA Astrophysics Data System (ADS)

    Yang, Shan; Evans, S. M.; Halliburton, L. E.; Slack, G. A.; Schujman, S. B.; Morgan, K. E.; Bondokov, R. T.; Mueller, S. G.

    2009-01-01

    An electron paramagnetic resonance (EPR) spectrum from Er3+ ions has been observed in a bulk single crystal of aluminum nitride (AlN). These Er3+ ions were introduced into the crystal during growth and had a concentration of approximately 2×1016 cm-3. The Er3+ EPR signal, monitored at 4.5 K, exhibits axial symmetry (the unique axis is parallel to the c axis in this wurtzite lattice) and shows well-resolved hyperfine splittings due to E167r nuclei. An absence of site splittings in the EPR angular dependence indicates that these erbium ions, replacing aluminum ions in the AlN crystal, have no nearby defects. Principal values for the g and hyperfine matrices are g∥=4.337, g⊥=7.647, |A∥|=454 MHz, and |A⊥|=796 MHz. Forbidden transitions, appearing in the low-field portion of the hyperfine spectrum when the magnetic field is rotated a few degrees away from the c axis, give |P|=7.8 MHz for the nuclear electric quadrupole parameter.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. ER Suspensions of Sulfonated Poly(Styrene-CO-Divinylbenzene) Particles

    NASA Astrophysics Data System (ADS)

    Kawakami, Toshihiro; Aizawa, Ryuji; Konishi, Masayoshi; Asako, Yoshinobu

    Two ER suspensions (ERF1 and ERF2) containing highly sulfonated poly(styrene-co-divinylbenzene) particles (ERP) were newly prepared. The ERP concentration was 20 wt% in ERF1 and 40 wt% in ERF2. The ER properties of the suspensions were investigated in view of applications to practical devices. The investigated properties were zero-field viscosity, dispersion stability, induced shear stress, current density, response time, shear rate and temperature dependence of the induced shear stress and current density, response time, shear rate and temperature dependence of the induced shear stress and the current density. electrical durability. In the results, it was found that ERF1 and ERF2 had a very high potential for practical applicatons. The remarkable characteristic of ERF1 was the very low zero-field viscosity of 35 mPa·s at 25°C. The remarkable characteristic of ERF2 was very large induced shear stress and under applying DC 4 kV/mm at 25°C, the induced shear stress was 5.1 kPa. As an application example, the ERFs can be efficiently used for an ER Cutting Machine incorporating variable speed rodless cylinders. The machine has worked smoothly for one and a half years, although the characteristic of control slightly changed.

  3. 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.

  4. 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.

  5. ER and PR signaling nodes during mammary gland development

    PubMed Central

    2012-01-01

    The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge. PMID:22809143

  6. 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.

  7. An Overview of ER-2 Platform Science during TC4

    NASA Astrophysics Data System (ADS)

    Platnick, S.; Newman, P. A.

    2007-12-01

    The NASA high-altitude ER-2 aircraft flew 11 science flight out of San Jose, Costa Rica during July and August 2007 as part of the NASA-sponsored Tropical Composition, Clouds and Climate Coupling Experiment (TC4). The ER-2 flew a remote sensing payload consisting of passive optical and microwave imagers (MAS/MASTER, CoSSIR, AMPR), a high spectral resolution IR imager (S-HIS), active sensors (CPL lidar, CRS and EDOP radars), spectral solar (SSFR) and IR flux radiometers, a microwave temperature profiler (MTP), and a visible video camera (MVIS). This suite of sensors provided a high spatial resolution simulator for cloud, aerosol, sounding, and trace gas retrieval capabilities from the "A-Train" constellation, in particular, the Aqua, CloudSat, and CALIPSO satellites. In this talk we present an overview of the ER-2 TC4 science and validation objectives, and a summary of the campaign accomplishments. Science goals included observations of convective system development, anvil cirrus property evolution (i.e., microphysics, optical properties, narrow and broadband radiative fluxes), tropical Tropopause Transition Layer (TTL) and subvisual cirrus detection and characterization, marine boundary layer cloud properties, aerosol transport and optical properties, and trace gas and atmospheric state characteristics. Coordination with the DC-8 and/or WB-57 aircrafts allowed for validation of various retrievals from these observations. Morning flights (due to adverse local afternoon weather conditions) included coordination with the Terra spacecraft when feasible.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

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

    NASA Astrophysics Data System (ADS)

    Najar, Adel; Omi, Hiroo; Tawara, Takehiko

    2014-07-01

    Polycrystalline Er-Sc silicates (Er x Sc2- x Si2O7 and Er x Sc2- x SiO5) were fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on SiO2/Si substrates by RF sputtering and thermal annealing at high temperature. The films were characterized by synchrotron radiation grazing incidence X-ray diffraction, cross-sectional transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate phase Er x Sc2- x Si2O7 is the dominant film, and Er and Sc are homogeneously distributed after thermal treatment because of the excess of oxygen from SiO2 interlayers. The Er concentration of 6.7 × 1021 atoms/cm3 was achieved due to the presence of Sc that dilutes the Er concentration and generates concentration quenching. During silicate formation, the erbium diffusion coefficient in the silicate phase is estimated to be 1 × 10-15 cm2/s at 1,250°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.

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

    PubMed Central

    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

  17. WatER: The proposed Water Elevation Recovery satellite mission

    NASA Astrophysics Data System (ADS)

    Alsdorf, D.; Mognard, N.; Rodriguez, E.; Participants, W.

    2005-12-01

    Surface fresh water is essential for life, yet we have surprisingly poor knowledge of the spatial and temporal dynamics of surface water storage and discharge globally. The core mission objective is to describe and understand the continental water cycle and the hydrological processes (e.g., floodplain hydraulics) at work in a river basin. The key question that will be answered by WatER is: "Where is water stored on Earth's land surfaces, and how does this storage vary in space and time?" WatER will facilitate societal needs by (1) improving our understanding of flood hazards; (2) freely providing water volume information to countries who critically rely on rivers that cross political borders; and (3) mapping the variations in water bodies that contribute to disease vectors (e.g., malaria). Conventional altimeter profiles are, without question, incapable of supplying the measurements needed to address scientific and societal questions. WatER will repeatedly measure the spatially distributed water surface elevations (h) of wetlands, rivers, lakes, reservoirs, etc. Successive h measurements yield dh/dt, (t is time), hence a volumetric change in water stored or lost. Individual images of h yield dh/dx (x is distance), hence surface water slope, which is necessary for estimating streamflow. WatER's main instrument is a Ka-band radar interferometer (KaRIN) which is the only technology capable of supplying the required imaging capability of h. KaRIN has a rich heritage based on (1) the many highly successful ocean observing radar altimeters, (2) the Shuttle Radar Topography Mission (SRTM), and (3) the development effort of the Wide Swath Ocean Altimeter (WSOA). The interferometric altimeter is a near-nadir viewing, 120 km wideswath based instrument that uses interferometric SAR processing of the returned pulses to yield single-look 5m azimuth and 10m to 70m range resolution, with an elevation accuracy of approximately 50 cm. Polynomial based averaging of heights along the

  18. 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

  19. 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

  20. Energy transfer and upconversion in Yb:YAG and Yb:Er:YAG

    SciTech Connect

    Lacovara, P.

    1992-01-01

    Energy transfer and upconversion have been studied in ytterbium, and ytterbium-erbium doped YAG (yttrium-aluminum garnet Y[sub 2]Al[sub 5]O[sub 12]). The energy-transfer probabilities were calculated for Yb-Yb, Yb-Er, and Er-Yb interactions, as well as for Er-Er and Yb-Er upconversion. The transfer of excitation from ytterbium to erbium was found experimentally to be efficient at Er concentrations above about 1%, with an Yb concentration of 6.5%. The Burshtein hopping model for donor migration-assisted transfer was applied to the Yb-Er system for different Er concentrations. Fitting the decay predicted by the Burshtein model to the Yb fluorescence gave a value for the Yb-Er dipole-dipole interaction strength which was in very close agreement with the calculated value, but discrepancies were noted for the donor-donor interaction. Upconversion was observed during pulsed measurements, and studies in detail with intense CW pumping. The Yb-Er upconversion was observed to dominate the Er-Er upconversion in the Yb-Er samples. Values for the Yb-Er and Er-Er ([sup 4]I[sub 1 1/2]) upconversion coefficients were determined from quantitative measurements of the [sup 4]S[sub 3/2] fluorescence which these processes generate, and measurements of the change in [sup 4]I[sub 1 1/2] population with increasing pump density. The quenching of nominally pure Yb:YAG by trace rare-earth impurities was also studied. The time dependence of the Yb fluorescence decay in some high-concentration samples suggested a fast quenching process active at high excited-ion densities, and a slower one at lower excited-ion densities. Study of the cooperative luminescence emitted by excited Yb pairs suggested a quenching mechanism acting preferentially on pairs. Sensitive Ar[sup +]-ion laser-pumped fluorescence measurements showed the presence of high ppm levels of several impurities, including Er, Tm and Cr. Pumping the ytterbium at 940 nm using pulsed and CW lasers revealed Er and Tm upconversion.

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

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration.

    PubMed

    Jia, Yichang; Jucius, Thomas J; Cook, Susan A; Ackerman, Susan L

    2015-02-18

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

  4. Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production.

    PubMed

    Leal, Nuno Santos; Schreiner, Bernadette; Pinho, Catarina Moreira; Filadi, Riccardo; Wiehager, Birgitta; Karlström, Helena; Pizzo, Paola; Ankarcrona, Maria

    2016-09-01

    Mitochondria are physically and biochemically in contact with other organelles including the endoplasmic reticulum (ER). Such contacts are formed between mitochondria-associated ER membranes (MAM), specialized subregions of ER, and the outer mitochondrial membrane (OMM). We have previously shown increased expression of MAM-associated proteins and enhanced ER to mitochondria Ca(2+) transfer from ER to mitochondria in Alzheimer's disease (AD) and amyloid β-peptide (Aβ)-related neuronal models. Here, we report that siRNA knockdown of mitofusin-2 (Mfn2), a protein that is involved in the tethering of ER and mitochondria, leads to increased contact between the two organelles. Cells depleted in Mfn2 showed increased Ca(2+) transfer from ER to mitchondria and longer stretches of ER forming contacts with OMM. Interestingly, increased contact resulted in decreased concentrations of intra- and extracellular Aβ40 and Aβ42 . Analysis of γ-secretase protein expression, maturation and activity revealed that the low Aβ concentrations were a result of impaired γ-secretase complex function. Amyloid-β precursor protein (APP), β-site APP-cleaving enzyme 1 and neprilysin expression as well as neprilysin activity were not affected by Mfn2 siRNA treatment. In summary, our data shows that modulation of ER-mitochondria contact affects γ-secretase activity and Aβ generation. Increased ER-mitochondria contact results in lower γ-secretase activity suggesting a new mechanism by which Aβ generation can be controlled. PMID:27203684

  5. 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

    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

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

    PubMed

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

    2014-04-01

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

  7. 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

  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. Ozone loss rates calculated along ER-2 flight tracks

    SciTech Connect

    Murphy, D.M. )

    1991-03-20

    Local ozone loss rates due to the ClO+ClO and BrO+ClO cycles are calculated using ClO, pressure, and temperature from in-situ aircraft measurements and representative BrO mixing ratios. Ozone loss during the vertical profiles executed by the ER-2 near 72{degree}S usually extended over a deep altitude range rather than reaching a maximum at the top of the profiles. This is due to the strong pressure dependence of the rate determining steps. In the Antarctic, very high ozone loss rates (>5{center dot}10{sup 6} cm{sup {minus}3} s{sup {minus}1}) were observed at altitudes with potential temperatures below 400 K, where advective exchange is likely to be much more rapid than at higher altitudes. On September 22, 1987, the ER-2 measured an ozone loss rate of aboutn 2.8 Dobson units (DU) per 12 sunlit hours in the 350-400 K range and 2.0 DU in the 400-450 K range near 72{degree}S. Rapid ozone loss in the Arctic did not extend below 400 K in the available data. The calculated average loss rate, which is nonlinear, in general depends on the order in which the terms are averaged. Loss rates calculated by averaging the ClO, pressure and temperature for up to 2,400 s (about 500 km) generally agree with the average of the local loss rate to within one percent except at the edge of the vortex, where the difference can be up to 30%. Adiabatic temperature and pressure effects nearly cancel. Thermal decomposition of Cl{sub 2}O{sub 2} was not important along sunlit portions of ER-2 flight tracks if equilibrium is assumed between ClO and Cl{sub 2}O{sub 2}. The effect of recalibration of the ClO data on the calculated loss rates is discussed.

  10. Planar array antenna for ERS-1 synthetic aperture radar

    NASA Astrophysics Data System (ADS)

    Wagner, R.

    1986-08-01

    To meet ERS-1 SAR specifications as to high gain, very narrow beamwidth in azimuth, and a slightly tapered shaped beam in elevation, a long narrow antenna was designed. At 5.3 GHz center frequency, the slotted waveguide antenna concept was selected over the reflector or the microstrip principles. Reasons are the low losses, good beamshaping capability, and mechanical compactness. A resonant array is chosen. All waveguides are made from metallized CFRP for reasons of low mass. The mechanical antenna system features a deployable configuration, plus the associated mechanisms. The performance verification concept, through analyses, and tests at different levels, is described.

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

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. Er/Tm:fiber laser system for coherent Raman microscopy.

    PubMed

    Coluccelli, Nicola; Kumar, Vikas; Cassinerio, Marco; Galzerano, Gianluca; Marangoni, Marco; Cerullo, Giulio

    2014-06-01

    We present a novel architecture for a fiber-based hybrid laser system for coherent Raman microscopy, combining an amplified Er:fiber femtosecond oscillator with a Tm:fiber amplifier boosting the power of the 2-μm portion of a supercontinuum up to 300 mW. This is enough to obtain, by means of nonlinear spectral compression, sub-20-cm(-1) wide pump and Stokes pulses with 2500-3300  cm(-1) frequency detuning and average power at the 100-mW level. Application of this system to stimulated Raman scattering microscopy is discussed. PMID:24875984

  14. Electromagnetic properties of vibrational bands in 170Er

    NASA Astrophysics Data System (ADS)

    DiJulio, D. D.; Cederkall, J.; Fahlander, C.; Ekström, A.; Golubev, P.; Mattsson, K.; Rudolph, D.; de Angelis, G.; Aydin, S.; Deo, A. Y.; Farnea, E.; Farrelly, G.; Geibel, K.; He, C.; Iwanicki, J.; Kempley, R.; Marginean, N.; Menegazzo, R.; Mengoni, D.; Orlandi, R.; Podolyak, Z.; Recchia, F.; Reiter, P.; Sahin, E.; Smith, J.; Söderström, P. A.; Torres, D. A.; Tveten, G. M.; Ur, C. A.; Valiente-Dobón, J. J.; Wendt, A.; Zielińska, M.

    2011-02-01

    Excited states of the nucleus 170Er have been studied by Coulomb excitation using the GASP γ -ray detector system at the Laboratori Nazionali di Legnaro. The ground-state band along with a low-lying ensuremath K^{π}=0^+ band and γ -vibrational band were populated during the experiment. Based on the measured γ -ray yields, a set of interband and intraband matrix elements has been extracted using the Coulomb excitation code GOSIA. The resulting E2 matrix elements are compared to collective model predictions.

  15. 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.

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

    PubMed

    Pereira, David M; Valentão, Patrícia; Correia-da-Silva, Georgina; Teixeira, Natércia; 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

  17. 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

  18. Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

    PubMed Central

    Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

    2015-01-01

    The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. A molecular switch for targeting between endoplasmic reticulum (ER) and mitochondria: conversion of a mitochondria-targeting element into an ER-targeting signal in DAKAP1.

    PubMed

    Ma, Yuliang; Taylor, Susan S

    2008-04-25

    dAKAP1 (AKAP121, S-AKAP84), a dual specificity PKA scaffold protein, exists in several forms designated as a, b, c, and d. Whether dAKAP1 targets to endoplasmic reticulum (ER) or mitochondria depends on the presence of the N-terminal 33 amino acids (N1), and these N-terminal variants are generated by either alternative splicing and/or differential initiation of translation. The mitochondrial targeting motif, which is localized between residues 49 and 63, is comprised of a hydrophobic helix followed by positive charges ( Ma, Y., and Taylor, S. (2002) J. Biol. Chem. 277, 27328-27336 ). dAKAP1 is located on the cytosolic surface of mitochondria outer membrane and both smooth and rough ER membrane. A single residue, Asp(31), within the first 33 residues of dAKAP1b is required for ER targeting. Asp(31), which functions as a separate motif from the mitochondrial targeting signal, converts the mitochondrial-targeting signal into a bipartite ER-targeting signal, without destroying the mitochondria-targeting signal. Therefore dAKAP1 possesses a single targeting element capable of targeting to both mitochondria and ER, with the ER signal overlapping the mitochondria signal. The specificity of ER or mitochondria targeting is determined and switched by the availability of the negatively charged residue, Asp(31). PMID:18287098

  8. A novel role of c-FLIP protein in regulation of ER stress response.

    PubMed

    Conti, Silvia; Petrungaro, Simonetta; Marini, Elettra Sara; Masciarelli, Silvia; Tomaipitinca, Luana; Filippini, Antonio; Giampietri, Claudia; Ziparo, Elio

    2016-09-01

    Cellular-Flice-like inhibitory protein (c-FLIP) is an apoptosis modulator known to inhibit the extrinsic apoptotic pathway thus blocking Caspase-8 processing in the Death Inducing Signalling Complex (DISC). We previously demonstrated that c-FLIP localizes at the endoplasmic reticulum (ER) and that c-FLIP-deficient mouse embryonic fibroblasts (MEFs) display an enlarged ER morphology. In the present study, we have addressed the consequences of c-FLIP ablation in the ER stress response by investigating the effects of pharmacologically-induced ER stress in Wild Type (WT) and c-FLIP-/- MEFs. Surprisingly, c-FLIP-/- MEFs were found to be strikingly more resistant than WT MEFs to ER stress-mediated apoptosis. Analysis of Unfolded Protein Response (UPR) pathways revealed that Pancreatic ER Kinase (PERK) and Inositol-Requiring Enzyme 1 (IRE1) branch signalling is compromised in c-FLIP-/- cells when compared with WT cells. We found that c-FLIP modulates the PERK pathway by interfering with the activity of the serine threonine kinase AKT. Indeed, c-FLIP-/- MEFs display higher levels of active AKT than WT MEFs upon ER stress, while treatment with a specific AKT inhibitor of c-FLIP-/- MEFs subjected to ER stress restores the PERK but not the IRE1 pathway. Importantly, the AKT inhibitor or dominant negative AKT transfection sensitizes c-FLIP-/- cells to ER stress-induced cell death while the expression of a constitutively active AKT reduces WT cells sensitivity to ER stress-induced death. Thus, our results demonstrate that c-FLIP modulation of AKT activity is crucial in controlling PERK signalling and sensitivity to ER stress, and highlight c-FLIP as a novel molecular player in PERK and IRE1-mediated ER stress response. PMID:27267061

  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. 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

  12. 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

  13. 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.

  14. Squashed embedding of E-R schemas in hypercubes

    NASA Astrophysics Data System (ADS)

    Baru, Chaitanya K.; Goel, Piyush

    1990-04-01

    We have been investigating an approach to parallel database processing based on treating Entity-Relationship (E-R) schema graphs as dataflow graphs. A prerequisite is to find appropriate embeddings of the schema graphs into a processor graph, in this case a hypercube. This paper studies a class of adjacency preserving embeddings that map a node in the schema graph into a subcube (relaxed squashed or RS embeddings) or into adjacent subcubes (relaxed extended squashed or RES embeddings) of a hypercube. The mapping algorithm is motivated by the technique used for state assignment in asynchronous sequential machines. In general, the dimension of the cube required for squashed embedding of a graph is called the weak cubical dimension or WCD of the graph. The RES embedding provides an RES-WCD of O(⌈log2n⌉) for a completely connected graph, Kn, and RS embedding provides an RS-WCD of O(⌈log2n⌉ + ⌈log2m⌉) for a completely connected bigraph, Km,n. Typical E-R graphs are incompletely connected bigraphs. An algorithm for embedding incomplete bigraphs is presented.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Hrd1 and ER-Associated Protein Degradation, ERAD, Are Critical Elements of the Adaptive ER Stress Response in Cardiac Myocytes

    PubMed Central

    Doroudgar, Shirin; Völkers, Mirko; Thuerauf, Donna J; Khan, Mohsin; Mohsin, Sadia; Respress, Jonathan L; Wang, Wei; Gude, Natalie; Müller, Oliver J; Wehrens, Xander HT; Sussman, Mark A; Glembotski, Christopher C

    2015-01-01

    Rationale Hrd1 is an endoplasmic reticulum (ER)-transmembrane E3 ubiquitin ligase that has been studied in yeast, where it contributes to ER protein quality control by ER-associated degradation (ERAD) of misfolded proteins that accumulate during ER stress. Neither Hrd1 nor ERAD have been studied in the heart, or in cardiac myocytes, where protein quality control is critical for proper heart function. Objective The objectives of this study were to elucidate roles for Hrd1 in ER stress, ERAD, and viability in cultured cardiac myocytes and in the mouse heart, in vivo. Methods and Results The effects of siRNA-mediated Hrd1 knockdown were examined in cultured neonatal rat ventricular myocytes. The effects of adeno-associated virus (AAV)-mediated Hrd1 knockdown and overexpression were examined in the hearts of mice subjected to pressure-overload induced pathological cardiac hypertrophy, which challenges protein-folding capacity. In cardiac myocytes, the ER stressors, thapsigargin (TG) and tunicamycin (TM) increased ERAD, as well as adaptive ER stress proteins, and minimally affected cell death. However, when Hrd1 was knocked down, TG and TM dramatically decreased ERAD, while increasing maladaptive ER stress proteins and cell death. In vivo, Hrd1 knockdown exacerbated cardiac dysfunction, and increased apoptosis and cardiac hypertrophy, while Hrd1 overexpression preserved cardiac function, and decreased apoptosis and attenuated cardiac hypertrophy in the hearts of mice subjected to pressure-overload. Conclusions Hrd1 and ERAD are essential components of the adaptive ER stress response in cardiac myocytes. Hrd1 contributes to preserving heart structure and function in a mouse model of pathological cardiac hypertrophy. PMID:26137860

  1. 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.

  2. Specific features of the nonradiative relaxation of Er{sup 3+} ions in epitaxial Si structures

    SciTech Connect

    Kudryavtsev, K. E. Kryzhkov, D. I.; Antonov, A. V.; Shengurov, D. V.; Shmagin, V. B.; Krasilnik, Z. F.

    2014-12-15

    The specific features of the nonradiative relaxation of Er{sup 3+} ions in Si:Er layers grown by sublimation molecular-beam epitaxy (SMBE) are studied. In Si:Er/Si diode structures containing precipitation-type emitting centers, a resonance photoresponse at the wavelength λ ≈ 1.5 μm is observed, which is indicative of the nonradiative relaxation of Er3+ ions via the energy back-transfer mechanism. Saturation of the erbium-related photocurrent is for the first time observed at high temperatures. This allows estimation of the concentration of Er centers that undergo relaxation via the above-mentioned back-transfer mechanism (N{sub 0} ≈ 5 × 10{sup 16} cm{sup −3}). In terms of order of magnitude, the estimated concentration N{sub 0} corresponds to the concentration of optically active Er ions upon excitation of the Si:Er layers by means of the recombination mechanism. The features of the nonradiative relaxation of Er{sup 3+} ions in Si:Er/Si structures with different types of emitting centers are analyzed.

  3. The PR status of the originating cell of ER/PR-negative mouse mammary tumors.

    PubMed

    Dong, J; Zhao, W; Shi, A; Toneff, M; Lydon, J; So, D; Li, Y

    2016-08-01

    Progesterone receptor (PR) is usually co-localized with estrogen receptor (ER) in normal mammary cells. It is not known whether ER/PR-negative human breast cancer arises from an ER/PR-negative cell or from an ER/PR-positive cell that later lost ER/PR. Using intraductal injection of a lentivirus to deliver both an oncogene (ErbB2) and a floxed green fluorescent protein (GFP) in PR(Cre/+)mice, whose Cre gene is under the control of the PR promoter, we were able to trace the PR status of the infected cells as they progressed to cancer. We found that the resulting early lesions stained negative for PR in most of the cells and usually retained GFP. The resulting tumors lacked ER and PR, and 75% (15/20) of them retained the GFP signal in all tumor cells, suggesting PR was never expressed throughout the evolution of a majority of these tumors. In conclusion, our data demonstrate that ErbB2-initiated ER/PR-negative mammary tumors primarily originate from the subset of the mammary epithelium that is negative for PR and probably ER as well. These findings also provide an explanation for why antihormonal therapy fails to prevent ER-negative breast cancers. PMID:26640140

  4. 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

  5. Unsaturated FAs prevent palmitate-induced LOX-1 induction via inhibition of ER stress in macrophages

    PubMed Central

    Ishiyama, Junichi; Taguchi, Ryoko; Akasaka, Yunike; Shibata, Saiko; Ito, Minoru; Nagasawa, Michiaki; Murakami, Koji

    2011-01-01

    Palmitic acid (PA) upregulates oxidized LDL receptor-1 (LOX-1), a scavenger receptor responsible for uptake of oxidized LDL (oxLDL), and enhances oxLDL uptake in macrophages. However, the precise underlying mechanism remains to be elucidated. PA is known to induce endoplasmic reticulum (ER) stress in various cell types. Therefore, we investigated whether ER stress is involved in PA-induced LOX-1 upregulation. PA induced ER stress, as determined by phosphorylation of PERK, eIF2α, and JNK, as well as induction of CHOP in macrophage-like THP-1 cells. Inhibitors [4-phenylbutyric acid (PBA), sodium tauroursodeoxycholate (TUDCA), and salubrinal] and small interfering RNA (siRNA) for the ER stress response decreased PA-induced LOX-1 upregulation. Thapsigargin, an ER stress inducer, upregulated LOX-1, which was decreased by PBA and TUDCA. We next examined whether unsaturated FAs could counteract the effect of PA. Both oleic acid (OA) and linoleic acid (LA) suppressed PA-induced LOX-1. Activation of the ER stress response observed in the PA-treated cells was markedly attenuated when the cells were cotreated with OA or LA. In addition, OA and LA suppressed thapsigargin-induced LOX-1 upregulation with reduced activation of ER stress markers. Our results indicate that activation of ER stress is involved in PA-induced LOX-1 upregulation in macrophages, and that OA and LA inhibit LOX-1 induction through suppression of ER stress. PMID:21078775

  6. Amalgam Surface Treatment by Different Output Powers of Er:YAG Laser:SEM Evaluation

    PubMed Central

    Hosseini, Mohammad Hashem; Hassanpour, Mehdi; Etemadi, Ardavan; Ranjbar Omrani, Ladan; Darvishpour, Hojat; Chiniforush, Nasim

    2015-01-01

    Introduction: The purpose of this study was to evaluate amalgam surfaces treated by different output powers of erbium-doped yttrium aluminum garnet (Er:YAG) laser by scanning electron microscope (SEM). Methods: Twenty-one amalgam blocks (8 mm × 8 mm, 3 mm thickness) were prepared by condensing silver amalgam (into putty impression material. After keeping them for 24 hours in distilled water, they were divided into 7 groups as follow: G1: Er:YAG laser (1 W, 50 mJ), G2: Er:YAG laser (2 W, 100 mJ), G3: Er:YAG laser (3 W, 150 mJ), G4: Sandblast, G5: Sandblast + Er:YAG laser (1 W, 50 mJ), G6: Sandblast +Er:YAG laser (2 W, 100 mJ) and G7: Sandblast +Er:YAG laser (3 W, 150 mJ). Then after preparation of all samples, they were examined by SEM. Results: The SEM results of amalgam surfaces treated by different output powers of Er:YAG laser showed some pitting areas with non-homogenous irregularities Conclusion: It seems that the application of sandblasting accompanied by Er:YAG laser irradiation can provide proper surface for bonding of orthodontic brackets. PMID:26705463

  7. 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

  8. Green up-converted luminescence in (Er3+-Yb3+) co-doped LiNbO3 crystals

    NASA Astrophysics Data System (ADS)

    Stoffel, M.; Rinnert, H.; Kokanyan, E.; Demirkhanyan, G.; Demirkhanyan, H.; Aillerie, M.

    2016-07-01

    Er3+ doped and (Er3+-Yb3+) co-doped LiNbO3 (LN) crystals grown by the Czochralski method are investigated by photoluminescence spectroscopy. Green up-converted luminescence is observed in Er3+ doped LN crystals under 980 nm excitation. This is explained by an energy transfer between two neighboring Er3+ ions. In (Er3+, Yb3+) co-doped LN crystals, the intensity of the green up-converted luminescence can be further enhanced suggesting that Yb3+ ions also contribute to the up-conversion process. Time resolved photoluminescence measurements clearly demonstrate that an efficient energy transfer occurs between Yb3+ and Er3+ ions. A theoretical model taking into account the contribution of both Er3+-Er3+ pairs and Yb3+-Er3+ pairs is able to describe correctly the decay of the up-converted luminescence.

  9. Molecular characterization of the ets-related human transcription factor ER81.

    PubMed

    Monté, D; Coutte, L; Baert, J L; Angeli, I; Stéhelin, D; de Launoit, Y

    1995-08-17

    The PEA3 group is a homogeneous group of the ets transcription factor family and is composed of three known members, PEA3, ERM and ER81, which, on the amino acid (AA) level, are more than 95% identical within the DNA-binding domain (the Ets domain), more than 85% within a 32 AA domain (the acidic domain) localized in the amino-terminus and almost 50% identical overall. By screening a human kidney cDNA library with a specific probe obtained from mouse ER81, we isolated two clones of 1.6 and 1.5 kb in length encoding a 458 AA open reading frame. When compared to mouse ER81, the present human ER81 lacks the last 13 AA of the acidic domain and the 5 AA contiguous to the carboxy-terminal part of the acidic domain. Of the 458 AA of the human ER81 protein, 97% are identical to mouse ER81. Gel shift analysis indicates that the full-length human ER81 protein is able to bind specifically to an oligonucleotide containing the binding sites recognized by most of the Ets proteins. By transient expression in RK13 mammalian cells, human ER81 protein transactivated a reporter plasmid containing Ets binding sites, indicating that this molecule is a bonafide transcriptional activator, while by expression in Cos-1 transfected cells, we detected the presence of human ER81 protein in the nucleus using immunocytochemistry. In human tissues, ER81 mRNA is very highly expressed in brain, highly expressed in testis, lung and heart, moderately in spleen, small intestine, pancreas and colon, weakly in liver, prostate and thymus, very weakly in skeletal muscle, kidney and ovary and not in placenta and peripheral blood leukocytes. Analysis of human solid or haematopoietic tumour cell lines showed that most of them did not express ER81 detectably. Database searches revealed that ETV1 mRNA is highly similar to human ER81 described here, although it contains the full-length acidic domain present in mouse ER81. By screening a genomic DNA library, we characterized the intron-exon junction within the

  10. 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

  11. 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.

  12. Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

    SciTech Connect

    Antonson, P.; Omoto, Y.; Humire, P.; Gustafsson, J.-A.

    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.

  13. Sorting Nexin 17 Regulates ApoER2 Recycling and Reelin Signaling

    PubMed Central

    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

  14. 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.

  15. 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.

  16. 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.

  17. Solar-pumped Er,Tm,Ho:YAG laser

    SciTech Connect

    Benmair, R.M.J.; Kagan, J.; Kalisky, Y.; Noter, Y.; Oron, M.; Shimony, Y.; Yogev, A. )

    1990-01-01

    Direct solar illumination was used to pump a 5-mm-diameter 62-mm exposed-length rod of Er,Tm,Ho:YAG to achieve a quasi-cw lasing of the Ho ion at an average power of 12 W. The solar radiation was chopped at a 20% duty cycle to avoid overloading of the cooling system. The peak power output was more than 65 W during the chopper's open times. The slope efficiency is 3.8%, and the threshold input energy is approximately 100 W. The laser was operated for long times (up to hours) while maintaining its performance. This is, to our knowledge, the first directly solar-pumped laser operating at 77 K.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Squashed embedding of E-R schemas in hypercubes

    SciTech Connect

    Baru, C.K.; Goel, P. )

    1990-04-01

    The authors have been investigating an approach to parallel database processing based on treating entity-relationship (E-R) schema graphs as dataflow graphs. A prerequisite is to find appropriate embeddings of the schema graphs into a processor graph, in this case a hypercube. This paper studies a class of adjacency preserving embeddings that map a node in the schema graph into a subcube (relaxed squashed or RS embeddings) or into adjacent subcubes (relaxed extended squashed or RES embeddings) of a hypercube. The mapping algorithm is motivated by the technique used for state assignment in asynchronous sequential machines. In general, the dimension of the cube required for squashed embedding of a graph is called the weak cubical dimension or WCD of the graph.

  3. Ice discharge from north and northeast Greenland using ERS data

    NASA Technical Reports Server (NTRS)

    Rignot, Eric

    1997-01-01

    Ice discharge from north and northeast Greenland glaciers was calculated at the grounding line using ERS radar interferometry data acquired during the tandem phase. The resulting estimates exceed the production of icebergs at the glacier fronts by a factor of 3.5. This large decrease in ice flux is attributed to extensive melting at the underside of the floating sections. When compared to the predicted grounding line ice discharge of an ice sheet in balance, the results show an excess of 28 cubic km/yr of ice lost to the ocean. The north and northeast sectors of the Greenland ice sheet are therefore thinning and contributing positively to sea-level rise.

  4. 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.

  5. 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.

  6. Nanoparticle doping for improved Er-doped fiber lasers

    NASA Astrophysics Data System (ADS)

    Baker, Colin C.; Friebele, E. Joseph; Askins, Charles G.; Hunt, Michael P.; Marcheschi, Barbara A.; Fontana, Jake; Peele, John R.; Kim, Woohong; Sanghera, Jasbinder; Zhang, Jun; Pattnaik, Radha K.; Merkle, Larry D.; Dubinskii, Mark; Chen, Youming; Dajani, Iyad A.; Mart, Cody

    2016-03-01

    A nanoparticle (NP) doping technique was used for making erbium-doped fibers (EDFs) for high energy lasers. The nanoparticles were doped into the silica soot of preforms, which were drawn into fibers. The Er luminescence lifetimes of the NP-doped cores are longer than those of corresponding solution-doped silica, and substantially less Al is incorporated into the NP-doped cores. Optical-to-optical slope efficiencies of greater than 71% have been measured. Initial investigations of stimulated Brillouin scattering (SBS) have indicated that SBS suppression is achieved by NP doping, where we observed a low intrinsic Brillouin gain coefficient, of ~1× 10-11 m/W and the Brillouin bandwidth was increased by 2.5x compared to fused silica.

  7. FINAL REPORT DOE/ER/63705-1

    SciTech Connect

    R.L. Street; F.L. Ludwig; Y. Chen

    2005-10-31

    Our DOE project is one of the efforts that comprised the Vertical Transport and Mixing Program [VTMX] of the Environmental Sciences Division of the Office of Biological and Environmental Research in Department of Energy and was supported originally by DOE grant ER 62847. The Advanced Regional Prediction System [ARPS] computer code was used to simulate flow in the Salt Lake Valley. The simulations provided evidence that atmospheric forcing interacts with the Jordan Narrows, the Traverse Range and other complex mountain terrain at the south end of the Salt Lake Valley to produce lee rotors, hydraulic jumps and other effects. This continuation grant was designed to allow us to complete our work on VTMX. The primary outcome of this grant was the completion of the dissertation of Dr. Ying Chen. In that work, several turbulence models were tested, a new surface vegetation model was developed, and Weather Research and Forecast code simulations were compared with ARPS runs.

  8. SEM investigation of Er:YAG laser apical preparation

    NASA Astrophysics Data System (ADS)

    Bǎlǎbuc, Cosmin; Todea, Carmen; Locovei, Cosmin; RǎduÅ£ǎ, Aurel

    2016-03-01

    Endodontic surgery involves the incision and flap elevation, the access to the root tip, its resection, the cavity retrograde preparation and filling it with biocompatible material that provides a good seal of the apex[1]. Apicoectomy is compulsory in endodontic surgery. The final stage involves the root retropreparation and the carrying out of the retrograde obturation. In order to perform the retrograde preparation the endodontist can use various tools such as lowspeed conventional handpieces, sonic and ultrasonic equipment. The ideal depth of the preparation should be 3 mm, exceeding this value may affect the long-term success of the obturation [2]. Resection at the depth of 3 mm reduces apical ramifications by 98% and lateral root canals by 93%. The ultrasonic retropreparation has numerous advantages compared to the dental drill. Firstly, the cavity will be in the axis of the tooth which implies a minimum destruction of the root canal morphology. The preparations are precise, and the cutting pattern is perpendicular to the long axis of the root, the advantage being the reduction in the number of dentinal tubules exposed at the resected area [3]. Therefore, the retrograde filling is the procedure when an inert and non-toxic material is compacted in the apically created cavity.[4,5]. The Er:YAG laser is the most common wavelength indicated for dental hard tissue preparation. Its natural selectivity offers a significant advantage compared to the conventional hard tissue preparation [6-9].The purpose of this in vitro study was to investigate the quality of Er:YAG laser apical third preparation using Scanning Electron Microscopy (SEM), in comparison with the conventional ultrasonic method.

  9. Design of Er:YAG laser blood-sampling device

    NASA Astrophysics Data System (ADS)

    Wu, Zhi-chao; Jin, Guang-yong; Tan, Xue-chun; Ling, Ming; Liang, Zhu

    2009-07-01

    Laser blood-sampling device is one of the foremost tasks in medicine domain. It has a lot of merits such as un-touching, avoiding infection, indolence, and fast healing etc. The Er:YAG laser with wavelength of 2.94μm which is just close to the absorbency peak of water can be strongly absorbed by water molecular, so it has very wide application value in clinical medicine. In the paper, based on the mutual action characters of the laser with 2.94μm wave length on biological tissues, such as high absorption, acting on surface, the design of a new type of laser blood-sampling device is introduced. According to the needs of practice, the main component of the blood-sampling device is the laser, which includes optical resonator, optical collector, pumping source, optical guidance and focusing system. All of them are designed in the paper, and the reflection index of output coupling mirror of laser is optimized, the laser threshold is reduced, and pumping efficiency is improved. Moreover, thermal effect of Er:YAG solid-state laser is analyzed and a reasonable cooling method is designed. As a result, an excellent laser blood- sampling is obtained, the maximum output power is about 1J, the optical to optical conversion efficiency is 1.2%. For the better production-grade, the cuprum-based conduction is adopt to eliminate heat, the precision modulation and fixing of the optical resonance is achieved by the special adjusting structure that not only improve the stability and reliability, but also reduce the size of laser bloodsampling device. The size is 110×190×320mm, the weight is about 5.8kg, and the laser blood- sampling efficiency is 100%.

  10. 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.

  11. 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.

  12. 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 mm×28 mm×9 mm and Er3+/Yb3+: Li3Ba2La3(WO4)8 crystal with dimensions of 52 mm×24 mm×8 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

  13. Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER in Budding Vesicles.

    PubMed

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

    2016-02-01

    The long-standing paradigm that all peroxisomal proteins are imported post-translationally into pre-existing peroxisomes has been challenged by the detection of peroxisomal membrane proteins (PMPs) inside the endoplasmic reticulum (ER). In mammals, the mechanisms of ER entry and exit of PMPs are completely unknown. We show that the human PMP PEX3 inserts co-translationally into the mammalian ER via the Sec61 translocon. Photocrosslinking and fluorescence spectroscopy studies demonstrate that the N-terminal transmembrane segment (TMS) of ribosome-bound PEX3 is recognized by the signal recognition particle (SRP). Binding to SRP is a prerequisite for targeting of the PEX3-containing ribosome•nascent chain complex (RNC) to the translocon, where an ordered multistep pathway integrates the nascent chain into the membrane adjacent to translocon proteins Sec61α and TRAM. This insertion of PEX3 into the ER is physiologically relevant because PEX3 then exits the ER via budding vesicles in an ATP-dependent process. This study identifies early steps in human peroxisomal biogenesis by demonstrating sequential stages of PMP passage through the mammalian ER. PMID:26572236

  14. 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

  15. 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...

  16. 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

  17. AMPK-independent inhibition of human macrophage ER stress response by AICAR.

    PubMed

    Boß, Marcel; Newbatt, Yvette; Gupta, Sahil; Collins, Ian; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR. PMID:27562249

  18. 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

  19. Upconversion properties of Er3+, Yb3+ and Tm3+ codoped fluorophosphate glasses.

    PubMed

    Liao, Meisong; Hu, Lili; Fang, Yongzheng; Zhang, Junjie; Sun, Hongtao; Xu, Shiqing; Zhang, Liyan

    2007-11-01

    Er3+, Yb3+ and Tm3+ codoped fluorophosphate glasses emitting blue, green and red upconversion luminescence at 970 nm laser diode excitation were studied. It was shown that Tm3+ behaves as the sensitizer to Er3+ for the green upconversion luminescence through the energy transfer process: Tm3+:3H4+Er3+:4I 15/2-->Er3+:4I 9/2+Tm3+:3H6, and for the red upconversion luminescence through the energy transfer process: Tm3+:3F4+Er3+:4I 11/2-->Tm3+:3H6+Er3+:4F 9/2. Moreover, Er3+ acts as quenching center for the blue upconversion luminescence of Tm3+. The sensitization of Tm3+ to Er3+ depends on the concentration of Yb3+. The intensity of blue, green and red emissions can be changed by adjusting the concentrations of the three kinds of rare earth ions. This research may provide useful information for the development of high color and spatial resolution devices and white light simulation. PMID:17329153

  20. Angiopoietin-2 promotes ER+ breast cancer cell survival in bone marrow niche.

    PubMed

    Han, Hyun Ho; Kim, Baek Gil; Lee, Joo Hyun; Kang, Suki; Kim, Ji Eun; Cho, Nam Hoon

    2016-08-01

    In estrogen receptor-positive (ER+) breast cancer, it is recognized that metastases may develop after a long period of dormancy. Bone marrow (BM) vascular niche is where the dormant tumor cells are most likely to reside. So far, it is not fully understood why the dormant tumor cells become proliferative and eventually generate tumor. We hypothesized that therapeutic or menopause-related estrogen depletion may be the switch behind dormant ER+ tumor cell awakening in BM. We utilized an existing experimental model of BM endothelial niche that can simulate ER+ tumor cell dormancy to test our hypothesis. In results, estrogen depletion paradoxically promoted ER+ tumor cell proliferation in the BM endothelial niche, and their molecular phenotype shifted from dormant to awaken. Following estrogen depletion, the BM niche cells produced angiopoietin-2 (ANGPT2), which destabilized niche endothelium by interfering ANGPT1/Tie2 signaling, and promoted ER+ tumor cell survival under estrogen deficiency via cell surface integrin &1. Knockdown of ANGPT2 completely negated ER+ tumor cell awakening in the niche. Furthermore, ANGPT2 expression in ER+ tumor human samples was associated with increased risk of distant metastasis only in those who underwent adjuvant estrogen depletion therapy, not in those who did not undergo adjuvant therapy. In conclusion, we demonstrate that ANGPT2 signaling activated after estrogen depletion paradoxically triggers ER+ tumor cell awakening from dormancy in their BM niche, partly indirectly via endothelial Tie2 receptor and partly directly via tumor cell surface integrin &1. PMID:27353038

  1. From ISBD(CF) to ISBD(ER): Process, Policy, and Provisions.

    ERIC Educational Resources Information Center

    Sandberg-Fox, Ann; Byrum, John D.

    1998-01-01

    In addition to setting out the process by which the International Standard Bibliographic Description for Computer Files [ISBD(CF)] was revised and the policies incorporated in the ISBD for Electronic Resources [ISBD(ER)], a detailed indication is provided of the stipulations of the ISBD(ER). Includes implications for AACR2R. (AEF)

  2. 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…

  3. A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro

    PubMed Central

    Kojima, Rieko; Endo, Toshiya; Tamura, Yasushi

    2016-01-01

    As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria. PMID:27469264

  4. Monomerization and ER Relocalization of GRASP Is a Requisite for Unconventional Secretion of CFTR.

    PubMed

    Kim, Jiyoon; Noh, Shin Hye; Piao, He; Kim, Dong Hee; Kim, Kuglae; Cha, Jeong Seok; Chung, Woo Young; Cho, Hyun-Soo; Kim, Joo Young; Lee, Min Goo

    2016-07-01

    Induction of endoplasmic reticulum (ER)-to-Golgi blockade or ER stress induces Golgi reassembly stacking protein (GRASP)-mediated, Golgi-independent unconventional cell-surface trafficking of the folding-deficient ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR). However, molecular mechanisms underlying this process remain elusive. Here, we show that phosphorylation-dependent dissociation of GRASP homotypic complexes and subsequent relocalization of GRASP to the ER play a critical role in the unconventional secretion of CFTR. Immunolocalization analyses of mammalian cells revealed that the Golgi protein GRASP55 was redistributed to the ER by stimuli that induce unconventional secretion of ΔF508-CFTR, such as induction of ER-to-Golgi blockade by the Arf1 mutant. Notably, the same stimuli also induced phosphorylation of regions near the C-terminus of GRASP55 and dissociation of GRASP homomultimer complexes. Furthermore, phosphorylation-mimicking mutations of GRASP55 induced the monomerization and ER relocalization of GRASP55, and these changes were nullified by phosphorylation-inhibiting mutations. These results provide mechanistic insights into how GRASP accesses the ER-retained ΔF508-CFTR and mediates the ER stress-induced unconventional secretion pathway. PMID:27062250

  5. 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.

  6. Survival of Er(a+) red cells in a patient with allo-anti-Era

    SciTech Connect

    Thompson, H.W.; Skradski, K.J.; Thoreson, J.R.; Polesky, H.F.

    1985-03-01

    /sup 51/Chromium-labeled Er(a+) red cells survived nearly normally (T1/2 of 21 days) in a patient with allo-anti-Era. Transfusion of Er(a+) blood was without significant reaction and did not affect the anti-Era titer.

  7. 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

  8. Thermal conductivity of near-stoichiometric (U, Er)O 2 solid solutions

    NASA Astrophysics Data System (ADS)

    Kim, Si-Hyung; Kim, Yeon-Gu; Kim, Han-Soo; Na, Sang-Ho; Lee, Young-Woo; Suhr, Dong-Soo

    2005-06-01

    Thermal diffusivities of UO 2 and UO 2 doped with 1, 3, 5, 7 and 10 mol % ErO 1.5 were measured in the range of 298-1673 K by a laser flash method and their thermal conductivities were calculated from the thermal diffusivity, the measured sample density and published specific heat capacity data. The temperature dependence of the thermal conductivity up to 1673 K in UO 2 and UO 2-doped with ErO 1.5 was found to be modeled well using the phonon conduction equation, K = ( A + BT) -1. The thermal conductivities of the UO 2 and (U, Er)O 2 solid solutions gradually decreased with the temperature. The thermal conductivity of the doped UO 2 decreased relative to UO 2 with an increase of ErO 1.5 content at low temperatures, while it was independent of the ErO 1.5 content at higher temperatures. The variation of parameters A and B as a function of ErO 1.5 content is found experimentally and it is found that the dependence of the thermal conductivity of (U, Er)O 2 on temperature up to 1673 K and on the ErO 1.5 content can be expressed as K={K}/{1+K(kAy+kByT)}.

  9. AMPK-independent inhibition of human macrophage ER stress response by AICAR

    PubMed Central

    Boß, Marcel; Newbatt, Yvette; Gupta, Sahil; Collins, Ian; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear. In a setting of hypoxia-potentiated inflammation induced by SFA palmitate, we found that the AMP-mimetic AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) potently suppressed upregulation of ER stress marker mRNAs and pro-inflammatory cytokines. Furthermore, AICAR inhibited macrophage ER stress responses triggered by ER-stressors thapsigargin or tunicamycin. Surprisingly, AICAR acted independent of AMPK or AICAR conversion to 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate (ZMP) while requiring intracellular uptake via the equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) CNT3. AICAR did not affect the initiation of the ER stress response, but inhibited the expression of major ER stress transcriptional effectors. Furthermore, AICAR inhibited autophosphorylation of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), while activating its endoribonuclease activity in vitro. Our results suggest that AMPK-independent inhibition of ER stress responses contributes to anti-inflammatory and anti-diabetic effects of AICAR. PMID:27562249

  10. Plasmodium falciparum Sec24 marks transitional ER that exports a model cargo via a diacidic motif

    PubMed Central

    Lee, Marcus C. S.; Moura, Pedro A.; Miller, Elizabeth A.; Fidock, David A.

    2009-01-01

    Summary Exit from the endoplasmic reticulum (ER) often occurs at distinct sites of vesicle formation known as transitional ER (tER) that are enriched for COPII vesicle coat proteins. We have characterized the organization of ER export in the malaria parasite, Plasmodium falciparum, by examining the localization of two components of the COPII machinery, PfSec12 and PfSec24a. PfSec12 was found throughout the ER, whereas the COPII cargo adaptor, PfSec24a, was concentrated at distinct foci that likely correspond to tER sites. These foci were closely apposed to cis-Golgi sites marked by PfGRASP-GFP, and upon treatment with brefeldin A they accumulated a model cargo protein via a process dependent on the presence of an intact diacidic export motif. Our data suggest that the cargo-binding function of PfSec24a is conserved and that accumulation of cargo in discrete tER sites depends upon positive sorting signals. Furthermore, the number and position of tER sites with respect to the cis-Golgi suggests a co-ordinated biogenesis of these domains. PMID:18410493

  11. A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro.

    PubMed

    Kojima, Rieko; Endo, Toshiya; Tamura, Yasushi

    2016-01-01

    As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria. PMID:27469264

  12. Novel intronic promoter in the rat ER alpha gene responsible for the transient transcription of a variant receptor.

    PubMed

    Tiffoche, C; Vaillant, C; Schausi, D; Thieulant, M L

    2001-09-01

    To analyze the molecular origin of an ER variant, the truncated ER product-1, transiently expressed at the proestrus in lactotrope cells, we generated a 2.5-kb sequence of a genomic region upstream and downstream the specific sequence truncated ER product-1. Genomic Southern blot analysis showed that truncated ER product-1 is spliced from a noncoding leader exon localized within the intron 4 of the ER alpha gene. Analysis of the promoter sequence revealed the presence of a major transcriptional start site, a canonical TATA box and putative cis regulatory elements for pituitary specific expression as well as an E-responsive element. In transient transfection, the truncated ER product-1 promoter was transcriptionally the most active in the lactotrope cell lines (MMQ). Analysis of truncated ER product-1 functionality showed that: 1) the protein inhibited ER alpha binding to the E-responsive element in electromobility shift assays, 2) inhibited the E2 binding to ER alpha in binding assays, 3) the truncated ER product-1/ER alpha complex antagonized the transcriptional activity elicited by E2, 4) nuclear localization of green fluorescent protein-ER alpha was altered in Chinese hamster ovary cell lines stably expressing truncated ER product-1. Collectively, these data demonstrated that the protein exerts full dominant negative activity against ER alpha. Moreover, truncated ER product-1/ER alpha complex also repressed the activity of all promoters tested to date, suggesting a general inhibitory effect toward transcription. In conclusion, the data suggest that truncated ER product-1 could regulate estrogen signaling via a specific promoter in lactotrope cells. PMID:11517190

  13. Electrochemical Preparation of Al-Li-Er-Tm Alloys by Co-reduction

    NASA Astrophysics Data System (ADS)

    Sun, Yi; Zhang, Milin; Han, Wei; Li, Mei; Ye, Ke; Yang, Yusheng; Yan, Yongde; Zhang, Meng

    2013-12-01

    The electrochemical behavior of Al, Li, Er, and Tm was investigated on tungsten electrodes in LiCl-KCl-AlF3-ErCl3-TmCl3 melts. The results indicated that the co-reduction of Al, Li, Er, and Tm occurs at current densities more negative than -0.469 A cm-2 or applied potentials more negative than -2.31 V. The strengthen phases of Al3Er and Al3Tm were prepared by galvanostatic electrolysis and characterized by X-ray diffraction and scanning electron microscopy. ICP-AES analyses showed that the content of lithium, erbium, and thulium in Al-Li-Er-Tm alloys could be controlled by adjusting AlF3 concentration and electrochemical parameters.

  14. Optical activation of Si nanowires using Er-doped, sol-gel derived silica

    SciTech Connect

    Suh, Kiseok; Shin, Jung H.; Park, Oun-Ho; Bae, Byeong-Soo; Lee, Jung-Chul; Choi, Heon-Jin

    2005-01-31

    Optical activation of Si nanowires (Si-NWs) using sol-gel derived Er-doped silica is investigated. Si-NWs of about 100 nm diameter were grown on Si substrates by the vapor-liquid-solid method using Au catalysts and H{sub 2} diluted SiCl{sub 4}. Afterwards, Er-doped silica sol-gel solution was spin-coated, and annealed at 950 deg. C in flowing N{sub 2}/O{sub 2} environment. Such Er-doped silica/Si-NWs nanocomposite is found to combine the advantages of crystalline Si and silica to simultaneously achieve both high carrier-mediated excitation efficiency and high Er{sup 3+} luminescence efficiency while at the same time providing high areal density of Er{sup 3+} and easy current injection, indicating the possibility of developing sol-gel activated Si-NWs as a material platform for Si-based photonics.

  15. Structural, electronic and mechanical properties of rare earth nitride-ErN: A first principles study

    SciTech Connect

    Murugan, A.; Rajeswarapalanichamy, R. Santhosh, M.; Priyanga, G. Sudha; Kanagaprabha, S.; Iyakutti, K.

    2015-06-24

    The structural, electronic and mechanical properties of rare earth nitride ErN is investigated by the first principles calculations based on density functional theory using the Vienna ab-initio simulation package. At ambient pressure ErN is stable in the ferromagnetic state with NaCl structure. The calculated lattice parameters are in good agreement with the available results. The electronic structure reveals that ErN is half metallic at normal pressure. A pressure-induced structural phase transition from NaCl (B1) to CsCl (B2) phase is observed in ErN. Ferromagnetic to non magnetic phase transition is predicted in ErN at high pressure.

  16. ERS-1 radial position refinement by dual crossover analysis with TOPEX/Poseidon

    NASA Astrophysics Data System (ADS)

    Carnochan, S.; Moore, P.; Ehlers, S.

    Achieving orbital accuracies in the radial direction for ERS-1 commensurate with those for TOPEX/Poseidon is of utmost importance for the integration of the two altimeter data sets. This paper outlines a procedure whereby the radial orbit error for ERS-1 is recovered as a time series expansion in the form of a finite Fourier series with additional terms for atmospheric drag, solar radiation pressure, and initial state vector mismodelling. Using a least squares collocation method with constraints derived from the JGM2 gravity field co-variance matrix, the radial error is recovered using both dual crossovers and ERS-1 single satellite crossovers. Aggregate arcs are then used to derive the ERS-1 orbit error over the repeat period of 35 days. The results are presented in the improvement of fit in the dual crossover, ERS-1 crossover and altimetry data sets as well as the recovery of an altimeter bias for the two satellites.

  17. Systematic study of excited 0+ states in the Er isotopes populated in the (p , t) reaction

    NASA Astrophysics Data System (ADS)

    Garrett, P. E.; Finlay, A.; Kisliuk, D.; Chagnon-Lessard, S.; Diaz Varela, A.; Dunlop, R.; Jamieson, D. S.; Leach, K. G.; Svensson, C. E.; Ball, G. C.; Triambak, S.; Faestermann, T.; Hertenberger, R.; Wirth, H.-F.

    2014-09-01

    The nature of excited 0+ states in well-deformed nuclei continue to pose a challenge in nuclear structure. Often, even the nature of the first excited 0+ state, 02+, is unclear and interpretations involving β vibrations, pairing excitations, two-phonon γ vibrations, etc., have been advanced with different degrees of success. A major issue historically has been lack of data on excited 0+ states. In light of this, the study of the Er isotopes has been extended via the 162Er and 164Er (p , t) reactions. The experiments were performed at the Maier-Leibnitz Laboratory using 22 MeV proton beams on highly-enriched targets of 162,164Er, and the reaction products were analyzed with the Q3D spectrograph. Strong populations of the 02+ states have been observed. The systematics of the strong population of the 0+ states in the Er (p , t) reactions sheds light on the underlying nature of these levels.

  18. 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.

  19. Structural, electronic and magnetic properties of Er implanted ZnO thin films

    NASA Astrophysics Data System (ADS)

    Murmu, P. P.; Kennedy, J.; Ruck, B. J.; Leveneur, J.

    2015-09-01

    We report the structural, electronic and magnetic properties of Er implanted and annealed ZnO thin films. The effect of annealing in oxygen-deficient and oxygen-rich conditions was investigated. Rutherford backscattering spectrometry results revealed that the Er atoms are located at the implantation depth of around 13 nm, and annealing conditions had no adverse effect on the Er concentration in the layer. Raman spectroscopy results showed peak related to E2(high) mode of ZnO indicating enhanced crystalline quality of the Er implanted and annealed ZnO films. X-ray absorption near edge spectroscopy results demonstrated pre-edge features in O K-edge which are attributed to the structural defects in the films. Room temperature magnetic ordering was observed in Er implanted and annealed films, and is mainly assigned to the intrinsic defects in ZnO.

  20. Power scaling of resonantly cladding-pumped, Yb-free, Er-doped LMA fiber lasers

    NASA Astrophysics Data System (ADS)

    Dubinskii, M.; Zhang, J.; Kudryashov, I.

    2009-04-01

    The results of the recent major efforts in power scaling of resonantly cladding-pumped Yb-free Er fiber lasers are presented. Commercially available Yb-free Er-doped large mode area Er60-20/125 (LMA) DC fibers were tested in two regimes: (i), as a booster amplifier in a single-frequency (SF) MOPA configuration and, (ii), in a Bragg grating (FBG) based narrowband fiber laser configuration. We obtained ˜28.5 W of output power at 1590 nm, the highest power reported so far out of Yb-free Er-doped LMA fiber with resonant cladding pumping. The achieved optical-to-optical conversion slope efficiency of ˜56.6% is also believed to be the highest efficiency ever reported from Yb-free Er-doped fiber laser with resonant cladding pumping.

  1. 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.

  2. Transient calnexin interaction confers long-term stability on folded K+ channel protein in the ER.

    PubMed

    Khanna, Rajesh; Lee, Eun Jeon; Papazian, Diane M

    2004-06-15

    We recently showed that an unglycosylated form of the Shaker potassium channel protein is retained in the endoplasmic reticulum (ER) and degraded by proteasomes in mammalian cells despite apparently normal folding and assembly. These results suggest that channel proteins with a native structure can be substrates for ER-associated degradation. We have now tested this hypothesis using the wild-type Shaker protein. Wild-type Shaker is degraded by cytoplasmic proteasomes when it is trapped in the ER and prevented from interacting with calnexin. Neither condition alone is sufficient to destabilize the protein. Proteasomal degradation of the wild-type protein is abolished when ER mannosidase I trimming of the core glycan is inhibited. Our results indicate that transient interaction with calnexin provides long-term protection from ER-associated degradation. PMID:15161937

  3. 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.

  4. Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress.

    PubMed

    Xu, S; Nam, S M; Kim, J-H; Das, R; Choi, S-K; Nguyen, T T; Quan, X; Choi, S J; Chung, C H; Lee, E Y; Lee, I-K; Wiederkehr, A; Wollheim, C B; Cha, S-K; Park, K-S

    2015-01-01

    Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca(2+) increase due to depletion of luminal ER Ca(2+). Palmitate-induced ER Ca(2+) depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca(2+) pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca(2+) depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca(2+) loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca(2+) depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA

  5. Enhancement of Er optical efficiency through bismuth sensitization in yttrium oxide

    SciTech Connect

    Scarangella, Adriana; Reitano, Riccardo; Franzò, Giorgia; Miritello, Maria; Priolo, Francesco

    2015-07-27

    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 Er{sup 3+} and Bi{sup 3+} valence states. In addition, we establish the ET occurrence from Bi{sup 3+} to Er{sup 3+} by the observed Bi{sup 3+} PL emission decrease and the simultaneous Er{sup 3+} photoluminescence (PL) emission increase. This was further confirmed by the coincidence of the Er{sup 3+} and Bi{sup 3+} 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 Bi{sup 3+} optical efficiency, the ET process between Bi{sup 3+} and Er{sup 3+} 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 Er{sup 3+} effective excitation cross section by more than three orders of magnitude with respect to the direct one, estimating a value of 5.3 × 10{sup −18} cm{sup 2}, similar to the expected Bi{sup 3+} 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.

  6. 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; Hung, Mien-Chie

    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.

  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

  8. ER stress and unfolded protein response in amyotrophic lateral sclerosis-a controversial role of protein disulphide isomerase.

    PubMed

    Jaronen, Merja; Goldsteins, Gundars; Koistinaho, Jari

    2014-01-01

    Accumulation of proteins in aberrant conformation occurs in many neurodegenerative diseases. Furthermore, dysfunctions in protein handling in endoplasmic reticulum (ER) and the following ER stress have been implicated in a vast number of diseases, such as amyotrophic lateral sclerosis (ALS). During excessive ER stress unfolded protein response (UPR) is activated to return ER to its normal physiological balance. The exact mechanisms of protein misfolding, accumulation and the following ER stress, which could lead to neurodegeneration, and the question whether UPR is a beneficial compensatory mechanism slowing down the neurodegenerative processes, are of interest. Protein disulphide isomerase (PDI) is a disulphide bond-modulating ER chaperone, which can also facilitate the ER-associated degradation (ERAD) of misfolded proteins. In this review we discuss the recent findings of ER stress, UPR and especially the role of PDI in ALS. PMID:25520620

  9. Coastal lee waves on ERS-1 SAR images

    NASA Astrophysics Data System (ADS)

    Zheng, Quanan; Yan, Xiao-Hai; Klemas, Vic; Ho, Chung-Ru; Kuo, Nan-Jung; Wang, Zongming

    1998-04-01

    Alternative dark-bright patterns on ERS-1 synthetic aperture radar (SAR) images of the west side of the Taiwan Strait taken on December 8, 1994, were recognized to be the sea surface signature of a coastal lee wave. Such waves are called coastal lee waves because they occur along the lee side of the coast. The coastal lee waves appeared in the form of a wave packet distributed within an offshore band 20-40 km wide. The first packet, which occurred in the northern portion of the observed area, contained six waves with variable wavelengths (defined as the spatial separation between two waves) from 1.7 to 2.7 km. The second packet, in the middle, contained 10 waves with a relatively uniform wavelength of 4.2 km. The third packet, in the southern portion, contained 17 waves with an average wavelength of 2.0 km. The crest lengths were from 20 to 80 km. Local meteorologic parameters observed simultaneously at Fuzhou, China, close to the imaged area, showed an offshore wind of 1.5-3.5 m/s and a land surface air temperature of 19°C, which was 4°C lower than the sea surface temperature (SST). Thus the lower atmospheric boundary conditions at imaging time were very favorable both for generating the land breeze circulation and small wind waves on the sea surface, which are in the Bragg-scattering wavelength band of the C band ERS-1 SAR. A physical model of a three-layer atmosphere was developed in order to explain how the land breeze circulation can generate the coastal lee waves. The results showed that the vertical velocity disturbance caused by the wind convergence at the land breeze frontal zone is of vital importance for the generation of coastal lee waves, and the model gave very good estimates of the processes observed. The SAR imaging mechanisms of the waves were analyzed in detail. The differences between coastal lee waves and ocean internal waves, which appear as similar alternative dark-bright patterns on SAR images, were also discussed.

  10. 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

  11. Quantitation of the immunocytochemical assay for estrogen receptor protein (ER-ICA) in human breast cancer by television imaging.

    PubMed

    Sklarew, R J; Pertschuk, L P

    1987-11-01

    A Quantimet 720D Image Analysis System has been programmed for light microscopic evaluation of the nuclear estrogen receptor distribution in frozen sections of human breast cancer stained by the peroxidase-antiperoxidase method using monoclonal antibodies to estrogen receptor protein (ER). This method provides precise criteria for distinguishing ER-positive and -negative cells and a sensitive and reproducible means for densitometric quantification of the staining patterns. Although imaging sequence and graphic analysis are automated by computer programs, light pen interaction provides supervision of feature selection. Imaging of the immunocytochemical assay (ER-ICA) in 50 patients revealed marked heterogeneity of nuclear estrogen receptor concentration varying over a nearly 100 fold concentration range. Various ER concentration patterns were evident: (I) distributions with a single peak (CV = 5%) present at various concentration levels; (II) bimodal distributions, revealing co-existent ER-positive and ER-negative subpopulations; (III) multimodal distributions with a number of resolvable concentration peaks; and (IV) highly skewed distributions with or without discernible peaks, frequently extending over the entire concentration range. Statistical methods of de-convolution were applied to determine the frequency and ER concentration characteristics of component subpopulations in the mosaic cases and for resolving the proportion of ER-positive and -negative cells. An approach for evaluating nuclear ER content in conjunction with ER concentration patterns in individual patients revealed whether spread in the ER concentration distribution resulted from differences in nuclear ER content or from variability in nuclear volume distribution. PMID:2821106

  12. 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.

  13. Optical activity and defect/dopant evolution in ZnO implanted with Er

    SciTech Connect

    Azarov, Alexander; Galeckas, Augustinas; Kuznetsov, Andrej; Monakhov, Edouard; Svensson, Bengt G.; Hallén, Anders

    2015-09-28

    The effects of annealing on the optical properties and defect/dopant evolution in wurtzite (0001) ZnO single crystals implanted with Er ions are studied using a combination of Rutherford backscattering/channeling spectrometry and photoluminescence measurements. The results suggest a lattice recovery behavior dependent on ion dose and involving formation/evolution of an anomalous multipeak defect distribution, thermal stability of optically active Er complexes, and Er outdiffusion. An intermediate defect band occurring between the surface and ion-induced defects in the bulk is stable up to 900 °C and has a photoluminescence signature around 420 nm well corresponding to Zn interstitials. The optical activity of the Er atoms reaches a maximum after annealing at 700 °C but is not directly associated to the ideal Zn site configuration, since the Er substitutional fraction is maximal already in the as-implanted state. In its turn, annealing at temperatures above 700 °C leads to dissociation of the optically active Er complexes with subsequent outdiffusion of Er accompanied by the efficient lattice recovery.

  14. 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

  15. Multiple Domains in PEX16 Mediate Its Trafficking and Recruitment of Peroxisomal Proteins to the ER.

    PubMed

    Hua, Rong; Gidda, Satinder K; Aranovich, Alexander; Mullen, Robert T; Kim, Peter K

    2015-08-01

    Peroxisomes rely on a diverse array of mechanisms to ensure the specific targeting of their protein constituents. Peroxisomal membrane proteins (PMPs), for instance, are targeted by at least two distinct pathways: directly to peroxisomes from their sites of synthesis in the cytosol or indirectly via the endoplasmic reticulum (ER). However, the extent to which each PMP targeting pathway is involved in the maintenance of pre-existing peroxisomes is unclear. Recently, we showed that human PEX16 plays a critical role in the ER-dependent targeting of PMPs by mediating the recruitment of two other PMPs, PEX3 and PMP34, to the ER. Here, we extend these results by carrying out a comprehensive mutational analysis of PEX16 aimed at gaining insights into the molecular targeting signals responsible for its ER-to-peroxisome trafficking and the domain(s) involved in PMP recruitment function at the ER. We also show that the recruitment of PMPs to the ER by PEX16 is conserved in plants. The implications of these results in terms of the function of PEX16 and the role of the ER in peroxisome maintenance in general are discussed. PMID:25903784

  16. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    PubMed Central

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

  17. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation.

    PubMed

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. PMID:27435961

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

    PubMed Central

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

    2015-01-01

    STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca2+ 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 Ca2+ influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca2+ 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 Ca2+ 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

  19. 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

  20. p53 and Translation Attenuation Regulate Distinct Cell Cycle Checkpoints during Endoplasmic Reticulum (ER) Stress*

    PubMed Central

    Thomas, Sally E.; Malzer, Elke; Ordóñez, Adriana; Dalton, Lucy E.; van ′t Wout, Emily F. A.; Liniker, Elizabeth; Crowther, Damian C.; Lomas, David A.; Marciniak, Stefan J.

    2013-01-01

    Cell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G1 phase, although recent studies have identified a novel ER stress G2 checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G2 delay involving CHK1 and a later induction of G1 arrest associated both with the induction of p53 target genes and loss of cyclin D1. We show that substitution of p53/47 for p53 impairs the ER stress G1 checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G2 progression prior to ultimate G1 arrest. PMID:23341460

  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. Optical activity and defect/dopant evolution in ZnO implanted with Er

    NASA Astrophysics Data System (ADS)

    Azarov, Alexander; Galeckas, Augustinas; Hallén, Anders; Kuznetsov, Andrej; Monakhov, Edouard; Svensson, Bengt G.

    2015-09-01

    The effects of annealing on the optical properties and defect/dopant evolution in wurtzite (0001) ZnO single crystals implanted with Er ions are studied using a combination of Rutherford backscattering/channeling spectrometry and photoluminescence measurements. The results suggest a lattice recovery behavior dependent on ion dose and involving formation/evolution of an anomalous multipeak defect distribution, thermal stability of optically active Er complexes, and Er outdiffusion. An intermediate defect band occurring between the surface and ion-induced defects in the bulk is stable up to 900 °C and has a photoluminescence signature around 420 nm well corresponding to Zn interstitials. The optical activity of the Er atoms reaches a maximum after annealing at 700 °C but is not directly associated to the ideal Zn site configuration, since the Er substitutional fraction is maximal already in the as-implanted state. In its turn, annealing at temperatures above 700 °C leads to dissociation of the optically active Er complexes with subsequent outdiffusion of Er accompanied by the efficient lattice recovery.

  3. Oxidation of thin ErSi 1.7 overlayers on Si(111)

    NASA Astrophysics Data System (ADS)

    Guerfi, N.; Tan, T. A. Nguyen; Veuillen, J. Y.; Lollman, D. B.

    The oxidation of ErSi 1.7 thin films, epitaxially grown on Si(111)(7×7) surfaces by solid phase epitaxy, has been investigated by X-ray and UV photoelectron spectroscopies. Oxidation has been carried out at room temperature under low pressure (≤ 2×10 -5mbar) and 1 atm of oxygen, and at 700°C under 2 × 10 -5 mbar of oxygen. In all cases, both Si and Er react with oxygen. At room temperature the reaction depends on the pressure. Under low pressure the silicide surface is rather inert: a chemisorption phase of oxygen on Si and Er is detected only after exposures < 10 3 langmuir. High oxygen pressure produces a thin layer of mixed SiO 2, Si su☐ides and Er 2O 3. At 700°C, SiO 2 and Er 2O 3 are simultaneously formed, thus implying the decomposition of the silicide. The oxide layer has a SiO 2 termination at the surface. Only about half of the decomposed Si atoms react with oxygen. The preferential oxidation of Er is attributed to the high value of the heat of formation of Er 2O 3. An oxidation mechanism is proposed.

  4. 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

  5. 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

  6. ER/Golgi Intermediates Acquire Golgi Enzymes by Brefeldin a–Sensitive Retrograde Transport in Vitro

    PubMed Central

    Lin, Chung-Chih; Love, Harold D.; Gushue, Jennifer N.; Bergeron, John J.M.; Ostermann, Joachim

    1999-01-01

    Secretory proteins exit the ER in transport vesicles that fuse to form vesicular tubular clusters (VTCs) which move along microtubule tracks to the Golgi apparatus. Using the well-characterized in vitro approach to study the properties of Golgi membranes, we determined whether the Golgi enzyme NAGT I is transported to ER/Golgi intermediates. Secretory cargo was arrested at distinct steps of the secretory pathway of a glycosylation mutant cell line, and in vitro complementation of the glycosylation defect was determined. Complementation yield increased after ER exit of secretory cargo and was optimal when transport was blocked at an ER/Golgi intermediate step. The rapid drop of the complementation yield as secretory cargo progresses into the stack suggests that Golgi enzymes are preferentially targeted to ER/Golgi intermediates and not to membranes of the Golgi stack. Two mechanisms for in vitro complementation could be distinguished due to their different sensitivities to brefeldin A (BFA). Transport occurred either by direct fusion of preexisting transport intermediates with ER/Golgi intermediates, or it occurred as a BFA-sensitive and most likely COP I–mediated step. Direct fusion of ER/Golgi intermediates with cisternal membranes of the Golgi stack was not observed under these conditions. PMID:10613904

  7. 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

  8. 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

  9. Optical spectra and analysis of Er3 + in silicon with C, O, and N impurities

    NASA Astrophysics Data System (ADS)

    Wortman, D. E.; Morrison, C. A.; Bradshaw, J. L.

    1997-09-01

    Photoluminescence (PL) spectra of Er3+ in an Er-doped silicon film were recorded at 2 and 77 K over the wavelength range from 1.52 to 1.68 μm, which includes optical transitions between the Er3+4I13/2 and 4I15/2 manifolds. These spectra were then analyzed to determine the nature of the electrostatic field at the site of the Er ion that governs the ion's optical behavior. The PL spectra were analyzed three different ways: by considering the Er3+ ions to be occupying sites of Td, C3, or D2d point group symmetry. Transition energies and magnetic dipole transition probabilities were calculated for each case by diagonalizing a Hamiltonian representing the free-ion and crystal-field interactions in a Russell-Saunders basis of states spanning the lowest 15 J multiplets of the 4f11 electronic configuration of Er3+. Crystal-field parameters were varied in each case to find the best agreement with the experiment. Our results showed that the site symmetry of the Er3+ ions most consistent with the data is D2d. For this case, the rms deviation between the experimental and calculated energy levels is 3.3 cm-1 with the calculated magnetic dipole transition probabilities in qualitative agreement with the experiment.

  10. Investigation of Er3+, Yb3+, Nd3+ doped yttrium calcium oxyborate for photon upconversion applications

    NASA Astrophysics Data System (ADS)

    Kalidasan, M.; Baskar, K.; Dhanasekaran, R.

    2016-07-01

    In this work, investigation have been done on polycrystalline yttrium calcium oxyborate (YCa4O(BO3)3) for the realization of existence of second harmonic generation and other photon upconversion processes as concurrent effect with the aid of Er, Yb, Nd trivalent lanthanide ions. Pure, Er:Yb co-doped and Er:Yb:Nd triply-doped YCa4O(BO3)3 samples were prepared through solid state reaction and the phase identification has been done using powder X-ray diffraction spectral analysis. FTIR spectra show that the dopants increases the absorption of functional groups and modifies the lattice vibrational modes of YCa4O(BO3)3. The spectral overlap of optical absorption bands of Er3+, Yb3+, Nd3+ ions in 840 nm-1070 nm region indicates the prospect of energy transfer between these ions. The photoluminescence spectrum of Er:Yb:Nd triply doped sample show good enhancement compared to pure and Er:Yb co-doped YCa4O(BO3)3 samples. In the photon upconversion test carried out using 1064 nm Nd:YAG laser YCa4O(BO3)3:Er:Yb:Nd sample produced green light with efficiency higher than the other two samples. Surface morphology of the samples was recorded using field emission scanning electron microscope and analysed. The elemental composition of the samples has been confirmed by energy dispersive X-ray spectral analysis.

  11. 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

  12. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+) and Negative (ER-) Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

    PubMed Central

    Semaan, Suzan M.; Wang, Xu; Marshall, Alan G.; Sang, Qing-Xiang Amy

    2012-01-01

    Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+) tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER-) tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining) and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples. PMID:22773931

  13. Study of luminescence properties of novel Er3+ single-doped and Er3+/Yb3+ co-doped tellurite glasses.

    PubMed

    Gao, Yuan; Nie, Qiu-Hua; Xu, Tie-Feng; Shen, Xiang

    2005-04-01

    The novel Er(3+) single-doped and Er(3+)/Yb(3+) co-doped tellurite glasses were prepared. The effect of Yb(2)O(3) concentration on absorption spectra, emission spectra and upconversion spectra of glasses were measured and investigated. The emission intensity, fluorescence full width at half maximum (FWHM) and upconversion luminescence of Er(3+) go up with the increasing concentration of Yb(3+) ions. The maximum FWHM of (4)I(13/2) --> (4)I(15/2) transition of Er(3+) is approximate 77 nm for 1.41 x 10(21)ions/cm(3) concentration of Yb(3+)-doped glass. The visible upconversion emissions at about 532, 546 and 659 nm, corresponding to the (2)H(11/2) --> (4)I(15/2), (4)S(3/2) --> (4)I(15/2) and (4)F(9/2) --> (4)I(15/2) transitions of Er(3+), respectively, were simultaneously observed under the excitation at 970 nm. Subsequently, the possible upconversion mechanisms and important role of Yb(3+) on the green and red emissions were discussed and compared. The results demonstrate that this kind of tellurite glass may be a potentially useful material for developing potential amplifiers and upconversion optical devices. PMID:15741130

  14. Highly sensitive optical thermometry based on the upconversion fluorescence from Yb3+/Er3+ codoped La2(WO4)3:Yb3+ ,Er3+ phosphor

    NASA Astrophysics Data System (ADS)

    Yang, Yan-min; Mi, Chao

    2013-12-01

    An optical temperature sensor based on Yb3+ and Er3+ codoped La2(WO4)3 phosphor for using in the high temperature region is discussed on the basis of fluorescence intensity ratio (FIR) method. The dependence of temperature on the upconversion green emission was intensive studied when the temperature increased from 300 K to 550 K under the excitation of 971 nm laser diode. The fluorescence intensity ratio of the two green emissions bands centered at 525 nm, 545 nm changed dramatically with the thermal treatment. By analyzing the experimental data according to the FIR method, the result on the thermometric property of La2(WO4)3:Yb3+, Er3+ was obtained and it shows that the sensitivity of La2(WO4)3:Yb3+, Er3+ reached the maximal value of about 0.0097 K-1 at the temperature of 510 K, even when the temperature was as high as 900 K, the sensitivity could still exceed 0.007 K-1. Results indicate that La2(WO4)3:Yb3+, Er3+ has higher sensitivity for thermometry in high temperature area. Owing to its good thermal stability, low synthesis cost and high sensitivity, La2(WO4)3: Yb3+, Er3+ phosphor has potential application in optical temperature sensing.

  15. 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

  16. Direct imaging of ER calcium with targeted-esterase induced dye loading (TED).

    PubMed

    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 Ca(2+) indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca(2+) 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 Ca(2+) 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 Ca(2+) indicator and a hydrophilic fluorescent dye/Ca(2+) 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. 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

  18. Autophagy regulation depends on ER homeostasis controlled by lipid droplets.

    PubMed

    Velázquez, Ariadna P; Graef, Martin

    2016-08-01

    Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane vesicular structures encapsulating cytoplasmic cargo for vacuolar turnover and recycling. The membrane rearrangements underlying nucleation, expansion, closure, and vacuolar fusion of autophagosomes are driven by multicomponent core autophagy machinery in cooperation with numerous factors involved in a variety of cellular processes. Our current understanding of the origin and contribution of diverse membrane sources to autophagosome biogenesis and of cellular functions enabling stress-appropriate autophagy responses critical for cell health and survival remains limited. Here, we summarize and discuss our recent findings analyzing the role of lipid droplets (LDs), conserved intracellular storage compartments for neutral lipids, for autophagy regulation. Our data indicate that LDs are dispensable as membrane sources, but fulfill critical functions for maintaining endoplasmic reticulum (ER) homeostasis, including buffering of newly synthesized fatty acids and maintenance of phospholipid composition, required for intact autophagy regulation and cell survival during nutrient stress. PMID:27245853

  19. Gamma spectrum following neutron capture in {sup 167}Er

    SciTech Connect

    Visser, D.; Khoo, T.L.; Lister, C.J.

    1995-08-01

    Statistical decay from a highly excited state samples all the lower-lying states and, hence, provides a sensitive measure of the level density. Pairing has a major impact on the level density, e.g. creating a pair gap between the 0- and 2-quasiparticle configurations. Hence the shape of the statistical spectrum contains information on pairing, and can be used to provide information on the reduction of pairing with thermal excitation energy. For this reason, we measured the complete spectrum of {gamma}rays following thermal neutron capture in {sup 167}Er. The experiment was performed at the Brookhaven reactor using Compton-suppressed Ge detectors from TESSA. The spectrum, which was corrected for detector response and efficiency, reveals primary (first-step, high-energy) transitions up to nearly 8 MeV, secondary (last-step, lower-energy) transitions, as we as a continuous statistical component. Effort was expanded to identify all lines from contaminant sources and an upper limit of 5% was tentatively set for their contributions. The spectral shape of the statistical spectrum will be compared with theoretical spectra obtained from a calculation of pairing which accounts for a stepwise reduction of the pair correlations as the number of quasiparticles increases. The primary lines which decay directly to the near-yrast states will also be used to deduce the level densities.

  20. Emergence of Chaotic Scattering in Ultracold Er and Dy

    NASA Astrophysics Data System (ADS)

    Maier, T.; Kadau, H.; Schmitt, M.; Wenzel, M.; Ferrier-Barbut, I.; Pfau, T.; Frisch, A.; Baier, S.; Aikawa, K.; Chomaz, L.; Mark, M. J.; Ferlaino, F.; Makrides, C.; Tiesinga, E.; Petrov, A.; Kotochigova, S.

    2015-10-01

    We show that for ultracold magnetic lanthanide atoms chaotic scattering emerges due to a combination of anisotropic interaction potentials and Zeeman coupling under an external magnetic field. This scattering is studied in a collaborative experimental and theoretical effort for both dysprosium and erbium. We present extensive atom-loss measurements of their dense magnetic Feshbach-resonance spectra, analyze their statistical properties, and compare to predictions from a random-matrix-theory-inspired model. Furthermore, theoretical coupled-channels simulations of the anisotropic molecular Hamiltonian at zero magnetic field show that weakly bound, near threshold diatomic levels form overlapping, uncoupled chaotic series that when combined are randomly distributed. The Zeeman interaction shifts and couples these levels, leading to a Feshbach spectrum of zero-energy bound states with nearest-neighbor spacings that changes from randomly to chaotically distributed for increasing magnetic field. Finally, we show that the extreme temperature sensitivity of a small, but sizable fraction of the resonances in the Dy and Er atom-loss spectra is due to resonant nonzero partial-wave collisions. Our threshold analysis for these resonances indicates a large collision-energy dependence of the three-body recombination rate.

  1. Magnetization Processes During FM Transitions of Supercooled Er Films

    NASA Astrophysics Data System (ADS)

    Durfee, C. S.; Flynn, C. P.

    2000-03-01

    FM transitions are generally accompanied by dimensional changes of the crystal lattice. In magnetic films, the in-plane dimensional changes are inhibited by clamping to the substrate, creating a rich variety of phenomena (e.g. supercooling, dislocation formation and motion, bowing of dislocations, and altered magnetization processes), which can be directly observed with x-rays. Here we characterize the magnetization processes exhibited by unstrained Er films. Below the Curie temperature, the film exhibits supercooling, remaining in a metastable non-FM state and only relaxing to the FM state when a magnetic field is applied. This occurs by two distinct processes. The first process, which broadens the x-ray line shape, is nucleation and growth of FM domains. The second, which produces no line broadening, is isotropic magnetization of the entire film. Once magnetized, the film remains in the FM state until the temperature is raised several degrees above the Curie temperature, at which point the film relaxes to the non-FM state via one of these two paths. This process depends on the temperature when the field is removed.

  2. X-ray measurement of magnetoelastic strain in epitaxial Er

    NASA Astrophysics Data System (ADS)

    Durfee, C. S.; Conover, M. J.; Flynn, C. P.

    1997-03-01

    Magnetic transitions are frequently accompanied by magnetoelastic distortions of the crystal lattice. In the case of epitaxially-grown thin magnetic films, however, distortions of the unit cell are potentially restricted by the clamping of the film to the substrate. In thicker epitaxial films (≈ 0.5 μ m), we expect that a film will not be rigidly clamped but will allow dislocations to absorb the lattice mismatch with the substrate. A thick epitaxial magnetic film in this limit offers a system to study dislocation formation and motion in the presence of a tunable field-induced mismatch between film and substrate. For this study, we have prepared strain-free Er films on sapphire by well-known MBE techniques, and have investigated magnetoelastic distortions using x-ray diffraction. X-ray measurements were performed using specially-constructed 40 kOe magnet dewar with x-ray windows. In-plane and perpendicular lattice parameters were measured at several applied magnetic fields, which allow the degree of clamping in the constrained direction to be directly measured. These strains will be discussed in the context of dislocation motion to accommodate lattice mismatch.

  3. Calculations of signature for Dy, Er, Yb nuclei

    SciTech Connect

    Mueller, W.F.; Jensen, H.J.; Reviot, W.

    1993-10-01

    Energy signature splitting {Delta}e` of rotational bands depends sensitively on deformation, pair correlations, and Fermi level in the particular nucleus. Calculating {Delta}e` is therefore very useful in understanding the experimentally observed properties of such bands. In principal, one can extract {Delta}e` from Total Routhian Surface (TRS) calculations as well as from the Cranked Shell Model (CSM). However, the codes available are not based on a fully self-consistent treatment of all critical parameters, deformation, pairing, and Fermi level. The TRS calculations, while modeling the deformation in a {open_quote}realistic{close_quotes} manner as a function of rotational frequency and changes in the quasiparticle configuration, have deficiencies particularly in the treatment of pairing. The CSM codes, on the other hand, estimate pairing and the location of the Fermi level more precisely than the TRS codes, but work under the assumption of a constant deformation. We have developed a method to calculate {Delta}e` that utilizes the most advanced features of both types of codes. This ensures that the best parameter values are used as input for calculating the routhians. As a test, we have used a series of odd-A Dy, Er, and Yb nuclei around A = 160 and compared the results for the vi{sub 13/2} shell with experimental data on {Delta}e`. Details of our method will be discussed and the comparison will be presented.

  4. 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.

  5. Evolution of mechanical properties in ErT2 films.

    SciTech Connect

    Browning, James Frederick; Bond, Gillian Mary; Knapp, James Arthur

    2010-04-01

    The mechanical properties of rare earth tritide films evolve as tritium decays into {sup 3}He, which forms bubbles that influence long-term film stability in applications such as neutron generators. Ultralow load nanoindentation, combined with finite-element modeling to separate the mechanical properties of the thin films from their substrates, has been used to follow the mechanical properties of model ErT{sub 2} films as they aged. The size of the growing {sup 3}He bubbles was followed with transmission electron microscopy, while ion beam analysis was used to monitor total T and {sup 3}He content. The observed behavior is divided into two regimes: a substantial increase in layer hardness but elasticity changed little over {approx}18 months, followed by a decrease in elastic stiffness and a modest decease in hardness over the final 24 months. We show that the evolution of properties is explained by a combination of dislocation pinning by the bubbles, elastic softening as the bubbles occupy an increasing fraction of the material, and details of bubble growth modes.

  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. Arctic Ocean Gravity Field Derived From ERS-1 Satellite Altimetry.

    PubMed

    Laxon, S; McAdoo, D

    1994-07-29

    The derivation of a marine gravity field from satellite altimetry over permanently ice-covered regions of the Arctic Ocean provides much new geophysical information about the structure and development of the Arctic sea floor. The Arctic Ocean, because of its remote location and perpetual ice cover, remains from a tectonic point of view the most poorly understood ocean basin on Earth. A gravity field has been derived with data from the ERS-1 radar altimeter, including permanently ice-covered regions. The gravity field described here clearly delineates sections of the Arctic Basin margin along with the tips of the Lomonosov and Arctic mid-ocean ridges. Several important tectonic features of the Amerasia Basin are clearly expressed in this gravity field. These include the Mendeleev Ridge; the Northwind Ridge; details of the Chukchi Borderland; and a north-south trending, linear feature in the middle of the Canada Basin that apparently represents an extinct spreading center that "died" in the Mesozoic. Some tectonic models of the Canada Basin have proposed such a failed spreading center, but its actual existence and location were heretofore unknown. PMID:17752757

  8. 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.

  9. Power scaling of resonantly pumped Yb-free Er-doped fiber laser

    NASA Astrophysics Data System (ADS)

    Dubinskii, M.; Zhang, J.; Ter-Mikirtychev, V.

    2009-05-01

    Even though Yb-doped fiber lasers are known to be the most powerful and most efficient among all fiber lasers, recent successes in the eye-safe ~1.5μm Yb-Er-doped fiber lasers (where Er is excited through Yb-Er energy transfer) are quite impressive. Output power of Yb-Er fiber lasers reached ~300 W level and their optical-to-optical efficiency, for somewhat lower power levels, is exceeding 40% [2]. Nevertheless, as far as real eye safety is concerned, multi-hundred Watt Yb-Er fiber lasers typically carry in their output a significant fraction of competing 1-μm Yb emission, which totally compromises an eye-safe side of the application. Ultimate efficiency and thermal management of Yb-Er approach are also suffering due to: (i), inefficiency of Yb-Er energy transfer and, (ii), gigantic ~40% quantum defect of Er-doped fiber pumped at 9XX-nm. Presented here are very recent and successful results on power scaling of resonantly pumped Yb-free Er-doped fiber lasers and amplifiers. We are reporting an Ybfree Er-doped cladding-pumped fiber power scaling to ~50 W with ~57% optical-tooptical efficiency [6] in a few first experimental steps. This is clear manifestation of scaling potential of this most efficient approach to high power eye-safe fiber laser. The only competing approach to scalable eye-safe fiber laser implements Tm3+-doped fibers pumped at ~790 nm while relying on well known "2-for-1" process leading to quite efficient excitation of the ~2μm Tm3+ laser operation [4]. This approach has operational optical-to-optical efficiency quantum limit of ~75% [4], while resonantly pumped Ybfree Er-doped fiber laser's optical-to-optical efficiency quantum limit exceeds 95% due to its low-quantum-defect (QD) pump-lase scheme. Significant scaling potential of resonantly-pumped Yb-free Er-doped fiber lasers and amplifiers sets a path to an eye-safe fiber laser concept with drastically relaxed thermal management and nearly diffraction limited beam quality at ~kW-=-class power

  10. Transverse momentum nonconservation at the ErAs/GaAs interface

    NASA Astrophysics Data System (ADS)

    Russell, K. J.; Appelbaum, Ian; Narayanamurti, V.; Hanson, M. P.; Gossard, A. C.

    2005-03-01

    Because ErAs , a semimetal, grows epitaxially on GaAs(100) , ErAs -base/ GaAs -collector metal-base transistors provide a uniquely simple system in which to study the interfacial transverse momentum conservation of hot electrons. This system is also of interest for metal-semiconductor superlattice thermal energy conversion devices that utilize ErAs as the interbarrier material. A key requirement for such devices to outperform bulk thermal energy converters is the nonconservation of transverse momentum. Our results, indicating total nonconservation of transverse momentum, could therefore lead to significantly more efficient thermal energy conversion devices.

  11. An update on increasing ER violence and what's being done about it.

    PubMed

    1992-07-01

    Violent incidents in the hospital emergency room are increasing in intensity throughout the country, endangering the lives of the medical staff, security officers, patients, and visitors. Much of the violence is attributed to the spread of gang and drug activity, along with overcrowded, understaffed ERs due to a depressed economy. This report covers recent incidents of ER violence and the public demands of ER physicians and nurses for increased security. We will also detail security measures--from training in the psychology of violence to installing state-of-the-art metal detectors--that hospitals are now utilizing as deterrents. PMID:10121340

  12. 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.

  13. THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH OPANA ER INTRAVENOUS ABUSE A Case Report.

    PubMed

    Jabr, Fadi I; Yu, Ling

    2016-01-01

    Thrombotic microangiopathy is characterized by endothelial changes and microvascular stenosis. Several entities such as pregnancy, infection, connective tissue diseases, and drugs are associated with secondary thrombotic microangiopathy. Recently, new reformulation of Opana ER had been associated with thrombotic microangiopathy when injected intravenously. Here, we report the case of a 37-year-old man who developed renal failure and hemolytic anemia secondary to Opana ER intravenous abuse. Renal biopsy pathology was consistent with thrombotic microangiopathy likely caused by Opana ER intravenous abuse. PMID:27169165

  14. [The design of intelligentized FES system on ERD/ERS signals].

    PubMed

    Wang, Ya; Zhou, Peng; Zhang, Shuang; Wang, Mingshi

    2007-10-01

    Our objective is the designing of a functional electrical stimulation (FES) system on event related desynchronization (ERD) and event related synchronization (ERS) signals. When the brain images the left-and right-leg movements, the ERD/ERS signals will appear. By characterization and characteristic classification, the ERD/ERS will be translated into the response control signal for operating the FES system to electrically stimulate the legs of motor disability. The result shows that the experiment is successful in electrically stimulating the legs of motor disability. PMID:18027717

  15. Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells

    PubMed Central

    Li, Lei; Haynes, M. Page; Bender, Jeffrey R.

    2003-01-01

    Estrogen receptor (ER) α variants have been identified in an array of nonendothelial cells. We previously demonstrated that estrogen rapidly induces nitric oxide release via a phosphatidylinositol 3-kinase/Akt/endothelial nitric-oxide synthase (eNOS) pathway in EA.hy926 cells (immortalized human endothelial cells), which express a 46-kDa ER. We now confirm that, due to alternative splicing, the 46-kDa endothelial cell protein (ER46) is an amino-terminal truncated product of full-length ERα (ER66). ER46 is expressed in the plasma membrane, cytosol, and nucleus of resting, estrogen-deprived cells. Flow cytometric and immunofluorescence microscopic analyses demonstrated that the ER46 C but not N terminus is Ab-accessible in the plasma membrane. Inhibition of palmitoylation with tunicamycin and [3H]palmitic acid labeling demonstrated an estrogen-induced, palmitoylation-dependent plasma membrane ER46 recruitment, with reorganization into caveolae. In reconstituted, estrogen-stimulated COS-7 (ER-null) cells, membrane ER46 more efficiently triggered membrane eNOS phosphorylation than ER66. Conversely, ER66 more efficiently mediated estrogen response element reporter-gene transactivation than ER46. These results demonstrate that ER46 is localized and further dynamically targeted to the plasma membrane in a palmitoylation-dependent manner. ER46 more efficiently modulates membrane-initiated estrogen actions, including eNOS activation, than full-length ER66. These findings may have important implications in vascular-specific targeting of estrogen receptor agonists. PMID:12682286

  16. Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

    PubMed Central

    Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

    2012-01-01

    Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target. PMID:22341523

  17. 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).

  18. 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

  19. 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.

  20. [Study on red up-conversion luminescence of fluoride glasses doped with Er3+, Yb3+ and Tm3+].

    PubMed

    Yan, Lei; Liu, Zheng-wei; Yang, Xiao-liang

    2005-06-01

    When the quality of Er2O3 is 10 times the former, the authors found that its character of up-conversion luminescence is distinct. Then the authors studied the luminescence system of Es3+ /Tm3+, Er3+ /Er3+ and Er3+ /Yb3+ /Tm3+ and their character of upconversion and fluorescence spectrum at 980 nm. In addition, the authors studied the relation between the three systems and the consistency of Er2O3. The authors found that the intensity of green and red light changed with the consistence of Er3+ in the experiment. It's the consistence of Er3+ that is the most causative. The chance is equal for each lanthanonion that makes up the luminescence system in the uniformity matter. With the distance between each pair of lanthanonions in the luminescence system is changed, the luminescence system and the color of the up-conversion luminescence also changed. PMID:16201349

  1. The Formation of Clusters and Nanocrystals in Er-Implanted Hexagonal Silicon Carbide

    NASA Astrophysics Data System (ADS)

    Kaiser, U.; Muller, D. A.; Chuvilin, A.; Pasold, G.; Witthuhn, W.

    2004-04-01

    Impurity atom cluster and nanocrystal formation in Er-implanted hexagonal SiC were studied using TEM and HAADF-STEM. Short interstitial loops were initially observed to form in the as-implanted layers. After annealing at 1600°C extended matrix defects (wide interstitial loops and voids), Er atom clusters and nanocrystals grew. The wide interstitial loops act as strong sinks capturing diffusing dopants that gather first in lines, then planes, and finally in three-dimensional ErSi2 nanocrystals. The unstrained nanocrystals have a hill-like shape and only two polarity-dependent orientations with respect to the matrix. One-, two-, and three-dimensional Er atom clusters were also identified. For the case of Ge implantation, again the wide interstitial loops act as sinks for the implanted Ge, representing the seeds of the nanocrystal.

  2. 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.

  3. Expression of Human Gaucher Disease Gene GBA Generates Neurodevelopmental Defects and ER Stress in Drosophila Eye

    PubMed Central

    Ito, Kumpei; Hanai, Shuji; Aizawa, Hidenobu; Kato, Tomoki; Kawasaki, Kazunori; Yamaguchi, Terumi; Ryoo, Hyung Don; Goto-Inoue, Naoko; Setou, Mitsutoshi; Tsuji, Shoji; Ishida, Norio

    2013-01-01

    Gaucher disease (GD) is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase (GlcCerase). The accumulation of its substrate, glucocylceramide (GlcCer) is considered the main cause of GD. We found here that the expression of human mutated GlcCerase gene (hGBA) that is associated with neuronopathy in GD patients causes neurodevelopmental defects in Drosophila eyes. The data indicate that endoplasmic reticulum (ER) stress was elevated in Drosophila eye carrying mutated hGBAs by using of the ER stress markers dXBP1 and dBiP. We also found that Ambroxol, a potential pharmacological chaperone for mutated hGBAs, can alleviate the neuronopathic phenotype through reducing ER stress. We demonstrate a novel mechanism of neurodevelopmental defects mediated by ER stress through expression of mutants of human GBA gene in the eye of Drosophila. PMID:23936319

  4. Skateboarding Mishaps Send 176 U.S. Kids to ERs Every Day

    MedlinePlus

    ... fullstory_158502.html Skateboarding Mishaps Send 176 U.S. Kids to ERs Every Day Protective gear is essential ... in Columbus, Ohio. The study included data for kids between 5 and 19 years old. All were ...

  5. 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.

  6. 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.

  7. ER Death Rate in U.S. Drops by Nearly Half

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159738.html ER Death Rate in U.S. Drops by Nearly Half Study ... July 6, 2016 (HealthDay News) -- Hospital emergency room deaths in the United States plummeted by nearly half ...

  8. ER Death Rate in U.S. Drops by Nearly Half

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_159738.html ER Death Rate in U.S. Drops by Nearly Half Study ... July 6, 2016 (HealthDay News) -- Hospital emergency room deaths in the United States plummeted by nearly half ...

  9. 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.

  10. 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.

  11. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

    SciTech Connect

    Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

    2015-11-25

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  12. Spikes in Blood Pressure Don't Always Need ER Care

    MedlinePlus

    ... medlineplus/news/fullstory_159343.html Spikes in Blood Pressure Don't Always Need ER Care Most cases ... June 13, 2016 (HealthDay News) -- If your blood pressure reading at a routine doctor's office visit is ...

  13. 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...

  14. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.

    PubMed

    Karanasios, Eleftherios; Walker, Simon A; Okkenhaug, Hanneke; Manifava, Maria; Hummel, Eric; Zimmermann, Hans; Ahmed, Qashif; Domart, Marie-Charlotte; Collinson, Lucy; Ktistakis, Nicholas T

    2016-01-01

    Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. PMID:27510922

  15. 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

  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. Skateboarding Mishaps Send 176 U.S. Kids to ERs Every Day

    MedlinePlus

    ... Mishaps Send 176 U.S. Kids to ERs Every Day Protective gear is essential for preventing injuries, experts ... hospital emergency rooms each year -- about 176 a day -- for skateboarding-related injuries. Fractures and dislocations were ...

  18. 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

  19. Spikes in Blood Pressure Don't Always Need ER Care

    MedlinePlus

    ... gov/news/fullstory_159343.html Spikes in Blood Pressure Don't Always Need ER Care Most cases ... June 13, 2016 (HealthDay News) -- If your blood pressure reading at a routine doctor's office visit is ...

  20. Just 6 Percent of Chest Pain Cases in ER Are Life-Threatening

    MedlinePlus

    ... Percent of Chest Pain Cases in ER Are Life-Threatening: Study Muscle strains, anxiety, gastrointestinal issues often ... than 6 percent of these patients suffer from life-threatening conditions such as a heart attack. Most ...

  1. 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 ...

  2. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles

    PubMed Central

    Karanasios, Eleftherios; Walker, Simon A.; Okkenhaug, Hanneke; Manifava, Maria; Hummel, Eric; Zimmermann, Hans; Ahmed, Qashif; Domart, Marie-Charlotte; Collinson, Lucy; Ktistakis, Nicholas T.

    2016-01-01

    Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. PMID:27510922

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. ER-2 lidar observations from the October 1986 fire cirrus experiment

    NASA Technical Reports Server (NTRS)

    Spinhirne, J. D.; Hlavka, D. L.; Hart, W. D.

    1988-01-01

    A description of the ER-2 lidar data characteristics and available products, plus flight times and locations is presented for the FIRE cirrus experiment of October 13 through November 2, 1986. The CALS airborne lidar was flown for this experiment on the NASA ER-2 high altitude aircraft. The primary objectives of the CALS observations were to intensively measure cirrus cloud top height and structure for basic cirrus studies and for validation of satellite cloud retrievals.

  14. Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic β cells.

    PubMed

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

    Pancreatic β cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic β cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redox state thereby disrupting correct disulfide bond formation and proper protein folding. mTOR signaling regulates many metabolic processes including protein synthesis, cell growth, survival and proliferation. Oxidative stress inhibits mTORC1, which is considered an important suppressor of mitochondrial oxidative stress in β cells, and ultimately, controls cell survival. The interplay between ER stress and mTORC1 is complicated, since the unfolded protein response (UPR) activation can occur upstream or downstream of mTORC1. Persistent activation of mTORC1 initiates protein synthesis and UPR activation, while in the later phase induces ER stress. Chronic activation of ER stress inhibits Akt/mTORC1 pathway, while under particular settings, acute activation of UPR activates Akt-mTOR signaling. Thus, modulating mitochondrial oxidative stress and ER stress via mTOR signaling may be an approach that will effectively suppress obesity- or glucolipotoxicity-induced metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). In this review, we focus on the regulations between mTOR signaling and mitochondrial oxidative or ER stress in pancreatic β cells. PMID:27185188

  15. 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

    2016-02-01

    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

  16. 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... RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.47 Election of the RLS by a widow(er) or parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly...

  17. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Election of the RLS by a widow(er) or parent... RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.47 Election of the RLS by a widow(er) or parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly...

  18. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Election of the RLS by a widow(er) or parent... RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.47 Election of the RLS by a widow(er) or parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly...

  19. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Election of the RLS by a widow(er) or parent... RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.47 Election of the RLS by a widow(er) or parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly...

  20. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Election of the RLS by a widow(er) or parent... RETIREMENT ACT LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.47 Election of the RLS by a widow(er) or parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly...

  1. The Er/Ki-67 Proportion in Breast Tumours - An Immunohistochemical Study

    PubMed Central

    Rai, M K

    2016-01-01

    Introduction Breast tumours are classified as benign, proliferative and invasive tumours. Estrogen hormone influences the proliferative activity and progression of the tumour. Estrogen Receptor (ER) status and proliferative index (Ki 67) are important histopathological factors in the development and prognosis of these tumours. Aim The present study was aimed to evaluate the variations in ER and Ki-67 expression in three broad categories of breast lesions namely benign breast disease, proliferative breast disease and malignant breast disease. Materials and Methods ER% and Ki-67% was evaluated on the histopathological tissues of 15 patients each of benign, proliferative and invasive breast tumours. The ER+/ Ki-67± ratio was calculated and the variation of expression between the three categories was analyzed using student’s t-test. Pearson’s coefficient of correlation was used to correlate ER and Ki-67 positivity within each category. Results The mean ER+/Ki-67+ in benign, proliferative and invasive tumours was 0.81, 0.87 and 1.42 respectively. A statistically significant difference in ER+/Ki-67+ proportions was observed between proliferative breast disease category and malignant breast disease category and also between benign breast disease category and malignant breast disease category (p<0.05). However, no significant difference was observed in benign breast disease category and proliferative breast disease category (p>0.05). A significant correlation was observed in proliferative breast disease and malignant breast disease categories. However, no significant correlation was observed in benign breast disease category Conclusion ER+/Ki-67+ ratio is an important determinant of the invasive breast cancer and can be used to differentiate invasive cancers from benign and proliferative breast tumours. PMID:27190810

  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. INTRAPUPAL TEMPERATURE VARIATION DURING ER,CR:YSGG ENAMEL IRRADIATION ON CARIES PREVENTION

    PubMed Central

    de Freitas, Patrícia Moreira; Soares-Geraldo, Débora; Biella-Silva, Ana Cristina; Silva, Amanda Verna; da Silveira, Bruno Lopes; Eduardo, Carlos de Paula

    2008-01-01

    Studies have shown the cariostatic effect of Er,Cr:YSGG (2.78 μm) laser irradiation on human enamel and have suggested its use on caries prevention. However there are still no reports on the intrapulpal temperature increase during enamel irradiation using parameters for caries prevention. The aim of this in vitro study was to evaluate the temperature variation in the pulp chamber during human enamel irradiation with Er,Cr:YSGG laser at different energy densities. Fifteen enamel blocks obtained from third molars (3 x 3 x 3 mm) were randomly assigned to 3 groups (n=5): G1 – Er,Cr:YSGG laser 0.25 W, 20 Hz, 2.84 J/cm2, G2 – Er,Cr:YSGG laser 0.50 W, 20 Hz, 5.68 J/cm2, G3 – Er,Cr:YSGG laser 0.75 W, 20 Hz, 8.52 J/cm2. During enamel irradiation, two thermocouples were fixed in the inner surface of the specimens and a thermal conducting paste was used. One-way ANOVA did not show statistically significant difference among the experimental groups (α=0.05). There was intrapulpal temperature variation ≤0.1°C for all irradiation parameters. In conclusion, under the tested conditions, the use of Er,Cr:YSGG laser with parameters set for caries prevention lead to an acceptable temperature increase in the pulp chamber. PMID:19089198

  4. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease.

    PubMed

    Celardo, I; Costa, A C; Lehmann, S; Jones, C; Wood, N; Mencacci, N E; Mallucci, G R; Loh, S H Y; Martins, L M

    2016-01-01

    Mutations in PINK1 and PARKIN cause early-onset Parkinson's disease (PD), thought to be due to mitochondrial toxicity. Here, we show that in Drosophila pink1 and parkin mutants, defective mitochondria also give rise to endoplasmic reticulum (ER) stress signalling, specifically to the activation of the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response (UPR). We show that enhanced ER stress signalling in pink1 and parkin mutants is mediated by mitofusin bridges, which occur between defective mitochondria and the ER. Reducing mitofusin contacts with the ER is neuroprotective, through suppression of PERK signalling, while mitochondrial dysfunction remains unchanged. Further, both genetic inhibition of dPerk-dependent ER stress signalling and pharmacological inhibition using the PERK inhibitor GSK2606414 were neuroprotective in both pink1 and parkin mutants. We conclude that activation of ER stress by defective mitochondria is neurotoxic in pink1 and parkin flies and that the reduction of this signalling is neuroprotective, independently of defective mitochondria. A video abstract for this article is available online in the supplementary information. PMID:27336715

  5. 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

  6. Comparison of urinary calculus fragmentation during Ho:YAG and Er:YAG lithotripsy

    NASA Astrophysics Data System (ADS)

    Kang, Hyun Wook; Lee, Ho; Teichman, Joel H.; Welch, A. J.

    2005-04-01

    We compared urinary calculus fragmentation with long pulsed Ho:YAG (λ= 2.12 μm) versus Er:YAG (λ = 2.94 μm) lasers. We measured the ablation width, depth, volume and efficiency as a function of pulse energy from calculus threshold energy to clinical energy typically used for Ho:YAG laser lithotripsy. Ablation effects were evaluated for three types of urinary calculi (calcium oxalate monohydrate, cystine, and uric acid), for single and multiple pulses applied at various optical energy levels. By means of comparing laser-induced crater topography and ablation volume for each stone type, the feasibility of Er:YAG laser lithotripsy was appraised. The Er:YAG laser pulse energy generated deeper and narrower crater shapes with relatively smooth contours whereas the Ho:YAG laser produced shallower and wider craters with irregular shapes. In terms of multiple pulses ablation, the Er:YAG produced larger ablation volume than Ho:YAG. The deeper crater induced by the Er:YAG was attributed to the higher absorption coefficient of stones at the 2.94 μm wavelength, and widening of crater by Ho:YAG was perhaps caused by lateral expansion of ablated material. Comparing the ablation efficiency, Er:YAG was superior to Ho:YAG for both single and five-pulses.

  7. 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.

  8. 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

  9. 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.

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

    PubMed Central

    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

  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. Improvement of the radial positioning of ERS-1 through dual crossover analysis with TOPEX/Poseidon

    NASA Astrophysics Data System (ADS)

    Carnochan, S.; Moore, P.; Ehlers, S.; Lam, C.; Woodworth, P.

    1994-01-01

    A method where both dual crossovers and single satellite crossovers are used in conjunction to determine the radial error for both Topology Ocean Experiment (TOPEX)/Poseidon and ERS-1 as a finite Fourier series, is outlined. The procedure is based on a time series expansion of the radial orbit error of ERS-1 expressed in terms of a finite Fourier series at frequencies of multiples of 1/501 cycles per revolution (for the 35 day repeat orbit), with additional terms for atmospheric drag and solar radiation pressure mismodeling as well as errors in the initial state vector. Refinement of the ERS-1 positioning is presented from solutions utilizing both the dual crossover data set by itself and in combination with ERS-1 crossover data. The zero frequency term or constant offset in the time series expansion of the ERS-1 radial orbit error is a measure of the difference between the so called altimeter biases on TOPEX/Poseidon and ERS-1. Preliminary results of this difference are presented and compared against results for both satellites from long arc orbits.

  13. Er:YAG Laser Dental Treatment of Patients Affected by Epidermolysis Bullosa

    PubMed Central

    Galeotti, Angela; D'Antò, Vincenzo; Gentile, Tina; Giancristoforo, Simona; Romeo, Umberto

    2014-01-01

    Aim. The purpose of this study was to evaluate the efficacy of Er:YAG laser used for treating hard dental tissue in patients with epidermolysis bullosa (EB). Methods. We report two cases of EB in which an Er:YAG laser was used for conservative treatments. In the first case, the Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to treat caries on a deciduous maxillary canine in an 8-year-old male patient affected by dystrophic EB. In the second case, we treated a 26-year-old female patient, affected by junctional EB, with generalized enamel hypoplasia, and an Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to remove the damaged enamel on maxillary incisors. Results. The use of the Er:YAG laser, with the appropriate energy, was effective in the selective removal of carious tissue and enamel hypoplasia. During dental treatment with the Er:YAG laser, patients required only a few interruptions due to the absence of pain, vibration, and noise. Conclusions. Laser treatment of hard dental tissues is a valuable choice for patients affected by EB since it is less invasive compared to conventional treatment, resulting in improved patient compliance. PMID:25431688

  14. 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.

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

    PubMed

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

    2015-05-01

    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

  16. KGW:Yb, Er single crystals growth for eye-safe lasers

    NASA Astrophysics Data System (ADS)

    Majchrowski, Andrzej; Mierczyk, Zygmunt; Kopczynski, Krzysztof; Kwasny, Miroslaw; Michalski, Edward; Zmija, Jozef

    2003-10-01

    KGd(WO4)2 (KGW) single crystals doped with Yb3+, Er3+, and (Yb3+; Er3+) were grown with use of Top Seeded Solution Growth (TSSG) technique. Growth was carried out on oriented seeds from self-flux containing 20 mol% of KGW dissolved in K2W2O7. The spectral properties and laser characteristics of obtained single crystals were investigated. Absorption spectra of Er3+ and Yb3+-doped KGW were measured in the spectral range 200 - 5000 nm at room temperature. Excitation and luminescence spectra were also recorded at room temperature with a JOBIN-YVON spectrofluorimeter using a diode laser (POLAROID 4300, 980 nm, 1 W) as an excitation source. The measurements of the lifetime of the Er3+ and Yb3+ ions in the upper laser level of the samples were made by the direct method with pulse excitation. Investigations of longitudinally pumped KGW:Yb,Er microlasers with various Yb3+ and Er3+ ions concentration, generating at 1.5 μm were carried out.

  17. 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.

  18. Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

    PubMed

    Chalil, Sreeda; Pierre, Nicolas; Bakker, Astrid D; Manders, Ralph J; Pletsers, Annelies; Francaux, Marc; Klein-Nulend, Jenneke; Jaspers, Richard T; Deldicque, Louise

    2015-12-25

    Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging. PMID:26551463

  19. Rotational bands in neutron-rich {sup 169,171,172}Er

    SciTech Connect

    Wu, C.Y.; Cline, D.; Simon, M.W.; Teng, R.; Vetter, K.; Carpenter, M.P.; Janssens, R.V.F.; Wiedenhoever, I.

    2004-07-01

    The neutron-rich {sup 169,171,172}Er nuclei were populated by few-neutron transfer reactions between {sup 170}Er and {sup 238}U at a near barrier energy. The spectroscopy of these Er isotopes was studied using prompt {gamma} rays correlated with delayed transitions or events involving at least three prompt transitions. The ground-state band of {sup 172}Er was populated up to spin 22{sup +} at an excitation energy of 5528 keV. Rotational bands built on the 1/2{sup -}[521], 5/2{sup -}[512], and 7/2{sup +}[633] neutron configurations in {sup 169,171}Er were extended to substantially higher spins than previously known. The signature splitting observed in these rotational bands is addressed within the framework of the particle-rotor model in terms of triaxiality and Coriolis attenuation. The signature inversion observed in the 5/2{sup -}[512] band is well reproduced by including the triaxial degree of freedom in the calculation. Attenuating the Coriolis interaction in the calculation is found to be necessary to reproduce the signature splitting observed in the 7/2{sup +}[633] band. A similar Coriolis attenuation also is needed to account for the signature splitting as well as the B(M1)/B(E2) ratios in the 7/2{sup +}[633] ground-state band in the neighboring N=99 isotones, {sup 167}Er and {sup 169}Yb.

  20. Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport.

    PubMed

    Eden, Emily R; Sanchez-Heras, Elena; Tsapara, Anna; Sobota, Andrzej; Levine, Tim P; Futter, Clare E

    2016-06-01

    Membrane contact sites between the ER and multivesicular endosomes/bodies (MVBs) play important roles in endosome positioning and fission and in neurite outgrowth. ER-MVB contacts additionally function in epidermal growth factor receptor (EGFR) tyrosine kinase downregulation by providing sites where the ER-localized phosphatase, PTP1B, interacts with endocytosed EGFR before the receptor is sorted onto intraluminal vesicles (ILVs). Here we show that these contacts are tethered by annexin A1 and its Ca(2+)-dependent ligand, S100A11, and form a subpopulation of differentially regulated contact sites between the ER and endocytic organelles. Annexin A1-regulated contacts function in the transfer of ER-derived cholesterol to the MVB when low-density lipoprotein-cholesterol in endosomes is low. This sterol traffic depends on interaction between ER-localized VAP and endosomal oxysterol-binding protein ORP1L, and is required for the formation of ILVs within the MVB and thus for the spatial regulation of EGFR signaling. PMID:27270042