An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors

PubMed Central

Pan, Yuan; Laird, Joseph G.; Yamaguchi, David M.; Baker, Sheila A.

2015-01-01

Purpose. Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. Methods. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. Results. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. Conclusions. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane. PMID:26030105

An overview on the strategies to exploit rice endosperm as production platform for biopharmaceuticals.

PubMed

Takaiwa, Fumio; Wakasa, Yuhya; Hayashi, Shimpei; Kawakatsu, Taiji

2017-10-01

Cereal seed has been utilized as production platform for high-value biopharmaceutical proteins. Especially, protein bodies (PBs) in seeds are not only natural specialized storage organs of seed storage proteins (SSPs), but also suitable intracellular deposition compartment for recombinant proteins. When various recombinant proteins were produced as secretory proteins by attaching N terminal ER signal peptide and C terminal KDEL endoplasmic reticulum (ER) retention signal or as fusion proteins with SSPs, high amounts of recombinant proteins can be predominantly accumulated in the PBs. Recombinant proteins bioencapsulated in PBs exhibit high resistance to digestive enzymes in gastrointestinal tract than other intracellular compartments and are highly stable at ambient temperature, thus allowing oral administration of PBs containing recombinant proteins as oral drugs or functional nutrients in cost-effective minimum processed formulation. In this review, we would like to address key factors determining accumulation levels of recombinant proteins in PBs. Understanding of bottle neck parts and improvement of specific deposition to PBs result in much higher levels of production of high quality recombinant proteins. Copyright © 2017. Published by Elsevier B.V.

The regulation of ER export and Golgi retention of ST3Gal5 (GM3/GM4 synthase) and B4GalNAcT1 (GM2/GD2/GA2 synthase) by arginine/lysine-based motif adjacent to the transmembrane domain.

PubMed

Uemura, Satoshi; Shishido, Fumi; Kashimura, Madoka; Inokuchi, Jin-ichi

2015-12-01

In the Golgi maturation model, the Golgi cisternae dynamically mature along a secretory pathway. In this dynamic process, glycosyltransferases are transported from the endoplasmic reticulum (ER) to the Golgi apparatus where they remain and function. The precise mechanism behind this maturation process remains unclear. We investigated two glycosyltransferases, ST3Gal5 (ST3G5) and B4GalNAcT1 (B4GN1), involved in ganglioside synthesis and examined their signal sequences for ER export and Golgi retention. Reports have suggested that the [R/K](X)[R/K] motif functions as an ER exporting signal; however, this signal sequence is insufficient in stably expressed, full-length ST3G5. Through further analysis, we have clarified that the (2)R(3)R(X)(5) (9)K(X)(3) (13)K sequence in ST3G5 is essential for ER export. We have named the sequence the R/K-based motif. On the other hand, for ER export of B4GN1, the homodimer formation in addition to the R/K-based motif is required for ER export suggesting the importance of unidentified lumenal side interaction. We found that ST3G5 R2A/R3A and K9A/K13A mutants localized not only in Golgi apparatus but also in endosomes. Furthermore, the amounts of mature type asparagine-linked (N)-glycans in ST3G5 R2A/R3A and K9A/K13A mutants were decreased compared with those in wild-type proteins, and the stability of the mutants was lower. These results suggest that the R/K-based motif is necessary for the Golgi retention of ST3G5 and that the retention is involved in the maturation of N-glycans and in stability. Thus, several basic amino acids located on the cytoplasmic tail of ST3G5 play important roles in both ER export and Golgi retention. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Trafficking-deficient hERG K+ channels linked to long QT syndrome are regulated by a microtubule-dependent quality control compartment in the ER

PubMed Central

Smith, Jennifer L.; McBride, Christie M.; Nataraj, Parvathi S.; Bartos, Daniel C.; January, Craig T.

2011-01-01

The human ether-a-go-go related gene (hERG) encodes the voltage-gated K+ channel that underlies the rapidly activating delayed-rectifier current in cardiac myocytes. hERG is synthesized in the endoplasmic reticulum (ER) as an “immature” N-linked glycoprotein and is terminally glycosylated in the Golgi apparatus. Most hERG missense mutations linked to long QT syndrome type 2 (LQT2) reduce the terminal glycosylation and functional expression. We tested the hypothesis that a distinct pre-Golgi compartment negatively regulates the trafficking of some LQT2 mutations to the Golgi apparatus. We found that treating cells in nocodazole, a microtubule depolymerizing agent, altered the subcellular localization, functional expression, and glycosylation of the LQT2 mutation G601S-hERG differently from wild-type hERG (WT-hERG). G601S-hERG quickly redistributed to peripheral compartments that partially colocalized with KDEL (Lys-Asp-Glu-Leu) chaperones but not calnexin, Sec31, or the ER golgi intermediate compartment (ERGIC). Treating cells in E-4031, a drug that increases the functional expression of G601S-hERG, prevented the accumulation of G601S-hERG to the peripheral compartments and increased G601S-hERG colocalization with the ERGIC. Coexpressing the temperature-sensitive mutant G protein from vesicular stomatitis virus, a mutant N-linked glycoprotein that is retained in the ER, showed it was not restricted to the same peripheral compartments as G601S-hERG at nonpermissive temperatures. We conclude that the trafficking of G601S-hERG is negatively regulated by a microtubule-dependent compartment within the ER. Identifying mechanisms that prevent the sorting or promote the release of LQT2 channels from this compartment may represent a novel therapeutic strategy for LQT2. PMID:21490315

Plasmids encoding therapeutic agents

DOEpatents

Keener, William K [Idaho Falls, ID

2007-08-07

Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

16 CFR Figure 8 to Part 1203 - Apparatus for Test of Retention System Strength

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Apparatus for Test of Retention System Strength 8 Figure 8 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT...—Apparatus for Test of Retention System Strength ER10MR98.008 ...

16 CFR Figure 8 to Part 1203 - Apparatus for Test of Retention System Strength

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Apparatus for Test of Retention System Strength 8 Figure 8 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT...—Apparatus for Test of Retention System Strength ER10MR98.008 ...

ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain.

PubMed

Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G M; Korneev, Sergei; Holthuis, Joost C M

2017-01-25

SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme's catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca 2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER.

ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain

PubMed Central

Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G. M.; Korneev, Sergei; Holthuis, Joost C. M.

2017-01-01

SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme’s catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER. PMID:28120887

GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain.

PubMed

Huang, Hung-Hsiang; Hassinen, Antti; Sundaram, Subha; Spiess, Andrej-Nikolai; Kellokumpu, Sakari; Stanley, Pamela

2015-09-15

Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology

PubMed Central

Pawar, Sumit; Ungricht, Rosemarie; Tiefenboeck, Peter; Leroux, Jean-Christophe

2017-01-01

Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER. PMID:28826471

Effect of Er:YAG Laser and Sandblasting in Recycling of Ceramic Brackets.

PubMed

Yassaei, Soghra; Aghili, Hossein; Hosseinzadeh Firouzabadi, Azadeh; Meshkani, Hamidreza

2017-01-01

Introduction: This study was performed to determine the shear bond strength of rebonded mechanically retentive ceramic brackets after recycling with Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser or sandblasting. Methods: Twenty-eight debonded ceramic brackets plus 14 intact new ceramic brackets were used in this study. Debonded brackets were randomly divided into 2 groups of 14. One group was treated by Er:YAG laser and the other with sandblasting. All the specimens were randomly bonded to 42 intact human upper premolars. The shear bond strength of all specimens was determined with a universal testing machine at a crosshead speed of 0.5 mm/min until bond failure occurred. The recycled bracket base surfaces were observed under a scanning electron microscope (SEM). Analysis of variance (ANOVA) and Tukey tests were used to compare the shear bond strength of the 3 groups. Fisher exact test was used to evaluate the differences in adhesive remnant index (ARI) scores. Results: The highest bond strength belonged to brackets recycled by Sandblasting (16.83 MPa). There was no significant difference between the shear bond strength of laser and control groups. SEM photographs showed differences in 2 recycling methods. The laser recycled bracket appeared to have as well-cleaned base as the new bracket. Although the sandblasted bracket photographs showed no remnant adhesives, remarkable micro-roughening of the base of the bracket was apparent. Conclusion: According to the results of this study, both Er:YAG laser and sandblasting were efficient to mechanically recondition retentive ceramic brackets. Also, Er:YAG laser did not change the design of bracket base while removing the remnant adhesives which might encourage its application in clinical practice.

Effect of Er:YAG Laser and Sandblasting in Recycling of Ceramic Brackets

PubMed Central

Yassaei, Soghra; Aghili, Hossein; Hosseinzadeh Firouzabadi, Azadeh; Meshkani, Hamidreza

2017-01-01

Introduction: This study was performed to determine the shear bond strength of rebonded mechanically retentive ceramic brackets after recycling with Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser or sandblasting. Methods: Twenty-eight debonded ceramic brackets plus 14 intact new ceramic brackets were used in this study. Debonded brackets were randomly divided into 2 groups of 14. One group was treated by Er:YAG laser and the other with sandblasting. All the specimens were randomly bonded to 42 intact human upper premolars. The shear bond strength of all specimens was determined with a universal testing machine at a crosshead speed of 0.5 mm/min until bond failure occurred. The recycled bracket base surfaces were observed under a scanning electron microscope (SEM). Analysis of variance (ANOVA) and Tukey tests were used to compare the shear bond strength of the 3 groups. Fisher exact test was used to evaluate the differences in adhesive remnant index (ARI) scores. Results: The highest bond strength belonged to brackets recycled by Sandblasting (16.83 MPa). There was no significant difference between the shear bond strength of laser and control groups. SEM photographs showed differences in 2 recycling methods. The laser recycled bracket appeared to have as well-cleaned base as the new bracket. Although the sandblasted bracket photographs showed no remnant adhesives, remarkable micro-roughening of the base of the bracket was apparent. Conclusion: According to the results of this study, both Er:YAG laser and sandblasting were efficient to mechanically recondition retentive ceramic brackets. Also, Er:YAG laser did not change the design of bracket base while removing the remnant adhesives which might encourage its application in clinical practice. PMID:28912939

Rab7a modulates ER stress and ER morphology.

PubMed

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

2018-05-01

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

Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.

PubMed

Jin, Hisayo; Mimura, Naoya; Kashio, Makiko; Koseki, Haruhiko; Aoe, Tomohiko

2014-01-01

Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence in order to evaluate the effect of a functional defect in an ER chaperone in multi-cellular organisms. Here we report that heterozygous mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The defect in retrieval of BiP by the KDEL receptor leads to impaired activities in quality control and autophagy, suggesting that functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases.

An ER-peroxisome tether exerts peroxisome population control in yeast

PubMed Central

Knoblach, Barbara; Sun, Xuejun; Coquelle, Nicolas; Fagarasanu, Andrei; Poirier, Richard L; Rachubinski, Richard A

2013-01-01

Eukaryotic cells compartmentalize biochemical reactions into membrane-enclosed organelles that must be faithfully propagated from one cell generation to the next. Transport and retention processes balance the partitioning of organelles between mother and daughter cells. Here we report the identification of an ER-peroxisome tether that links peroxisomes to the ER and ensures peroxisome population control in the yeast Saccharomyces cerevisiae. The tether consists of the peroxisome biogenic protein, Pex3p, and the peroxisome inheritance factor, Inp1p. Inp1p bridges the two compartments by acting as a molecular hinge between ER-bound Pex3p and peroxisomal Pex3p. Asymmetric peroxisome division leads to the formation of Inp1p-containing anchored peroxisomes and Inp1p-deficient mobile peroxisomes that segregate to the bud. While peroxisomes in mother cells are not released from tethering, de novo formation of tethers in the bud assists in the directionality of peroxisome transfer. Peroxisomes are thus stably maintained over generations of cells through their continued interaction with tethers. PMID:23900285

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

PubMed

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

2018-05-25

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

Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

PubMed

Sharma, Parveen; Ignatchenko, Vladimir; Grace, Kevin; Ursprung, Claudia; Kislinger, Thomas; Gramolini, Anthony O

2010-07-09

Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase, which transports Ca(2+) into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation. Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO) annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins. We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly

PubMed Central

Vavassori, Stefano; Cortini, Margherita; Masui, Shoji; Sannino, Sara; Anelli, Tiziana; Caserta, Imma R.; Fagioli, Claudio; Mossuto, Maria F.; Fornili, Arianna; van Anken, Eelco; Degano, Massimo; Inaba, Kenji; Sitia, Roberto

2013-01-01

Summary To warrant the quality of the secretory proteome, stringent control systems operate at the endoplasmic reticulum (ER)-Golgi interface, preventing the release of nonnative products. Incompletely assembled oligomeric proteins that are deemed correctly folded must rely on additional quality control mechanisms dedicated to proper assembly. Here we unveil how ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as IgM and adiponectin. At neutral, ER-equivalent pH, the ERp44 carboxy-terminal tail occludes the substrate-binding site. At the lower pH of the cisGolgi, conformational rearrangements of this peptide, likely involving protonation of ERp44’s active cysteine, simultaneously unmask the substrate binding site and −RDEL motif, allowing capture of orphan secretory protein subunits and ER retrieval via KDEL receptors. The ERp44 assembly control cycle couples secretion fidelity and efficiency downstream of the calnexin/calreticulin and BiP-dependent quality control cycles. PMID:23685074

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

PubMed

Greig, Sarah L; Keating, Gillian M

2015-07-01

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

Spider dragline silk proteins in transgenic tobacco leaves: accumulation and field production.

PubMed

Menassa, Rima; Zhu, Hong; Karatzas, Costas N; Lazaris, Anthoula; Richman, Alex; Brandle, Jim

2004-09-01

Spider dragline silk is a unique biomaterial and represents nature's strongest known fibre. As it is almost as strong as many commercial synthetic fibres, it is suitable for use in many industrial and medical applications. The prerequisite for such a widespread use is the cost-effective production in sufficient quantities for commercial fibre manufacturing. Agricultural biotechnology and the production of recombinant dragline silk proteins in transgenic plants offer the potential for low-cost, large-scale production. The purpose of this work was to examine the feasibility of producing the two protein components of dragline silk (MaSp1 and MaSp2) from Nephila clavipes in transgenic tobacco. Two different promoters, the enhanced CaMV 35S promoter (Kay et al., 1987) and a new tobacco cryptic constitutive promoter, tCUP (Foster et al., 1999) were used, in conjunction with a plant secretory signal (PR1b), a translational enhancer (alfalfa mosaic virus, AMV) and an endoplasmic reticulum (ER) retention signal (KDEL), to express the MaSp1 and MaSp2 genes in the leaves of transgenic plants. Both genes expressed successfully and recombinant protein accumulated in transgenic plants grown in both greenhouse and field trials.

SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum

PubMed Central

Nogueira, Cristina; Erlmann, Patrik; Villeneuve, Julien; Santos, António JM; Martínez-Alonso, Emma; Martínez-Menárguez, José Ángel; Malhotra, Vivek

2014-01-01

TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18. DOI: http://dx.doi.org/10.7554/eLife.02784.001 PMID:24842878

The foldase CYPB is a component of the secretory pathway of Aspergillus niger and contains the endoplasmic reticulum retention signal HEEL.

PubMed

Derkx, P M; Madrid, S M

2001-12-01

Here we report the isolation and characterization of the cypB gene from Aspergillus niger. The cypB gene encodes a protein with a predicted molecular weight of 20.7 kDa, which shows a high degree of identity to the cyclophilin family of peptidyl prolyl cis-trans isomerases (PPIases) from other eukaryotes. The 5' untranslated region of cypB includes three sequences resembling UPREs (unfolded protein response elements). The expression of cypB is upregulated by tunicamycin and DTT, suggesting that at least one UPRE is functional. The CYPB protein also has a 23-amino acid sequence which serves to target the protein to the endoplasmic reticulum (ER), and the ER retention sequence HEEL. CYPB-(His)(6) was expressed in Escherichia coli; the purified protein is capable of isomerizing a substrate peptide in vitro. This is also the first report to show that C-terminal addition of the sequence HEEL is sufficient to ensure retention of the green fluorescent protein (GFP) within the ER.

Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors

PubMed Central

Chandramohan, Vidyalakshmi; Bao, Xuhui; Kaneko, Mika Kato; Kato, Yukinari; Keir, Stephen T.; Szafranski, Scott E.; Kuan, Chien-Tsun; Pastan, Ira H.; Bigner, Darell D.

2013-01-01

Current study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG, and D08-0493MG) and medulloblastoma (D283MED, D425MED, and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to Pseudomonas exotoxin A, carrying a C-terminal KDEL peptide (NZ-1-PE38KDEL). The immunotoxin was further stabilized by a disulfide (ds) bond between the heavy-chain and light-chain variable regions as the construct NZ-1-(scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1-(scdsFv)-PE38KDEL and NZ-1 antibody, for podoplanin peptide was 2.1×10−8 M, 8.0×10−8 M, and 3.9×10−10 M, respectively. In a protein stability assay, NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity while that of NZ-1-PE38KDEL declined to 13% of its initial levels after incubation at 37°C for 3 days. In vitro cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG, D08-0493MG, and in the medulloblastoma D283MED, D425MED, and DOAY xenografts and cell line. The NZ-1-(scdsFv)-PE38KDEL immunotoxin was highly cytotoxic, with an IC50 in the range of 1.6–29 ng/mL. Significantly, NZ-1-(scdsFv)-PE38KDEL demonstrated tumor-growth delay, averaging 24 days (P<0.001) and 21 days (P<0.001) in D2159MG and D283MED in vivo tumor models, respectively. Crucially, in the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41% increase in survival (P≤0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL exhibited significant potential as a targeting agent for malignant brain tumors. PMID:23115013

Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.

PubMed

Chandramohan, Vidyalakshmi; Bao, Xuhui; Kato Kaneko, Mika; Kato, Yukinari; Keir, Stephen T; Szafranski, Scott E; Kuan, Chien-Tsun; Pastan, Ira H; Bigner, Darell D

2013-05-15

Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to Pseudomonas exotoxin A, carrying a C-terminal KDEL peptide (NZ-1-PE38KDEL). The immunotoxin (IT) was further stabilized by a disulfide (ds) bond between the heavy-chain and light-chain variable regions as the construct NZ-1-(scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1-(scdsFv)-PE38KDEL and NZ-1 antibody for podoplanin peptide was 2.1 × 10(-8) M, 8.0 × 10(-8) M and 3.9 × 10(-10) M, respectively. In a protein stability assay, NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity, whereas that of NZ-1-PE38KDEL declined to 13% of its initial levels after incubation at 37°C for 3 days. In vitro cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG and D08-0493MG, and in the medulloblastoma D283MED, D425MED and DOAY xenografts and cell line. The NZ-1-(scdsFv)-PE38KDEL IT was highly cytotoxic, with an 50% inhibitory concentration in the range of 1.6-29 ng/ml. Significantly, NZ-1-(scdsFv)-PE38KDEL demonstrated tumor growth delay, averaging 24 days (p < 0.001) and 21 days (p < 0.001) in D2159MG and D283MED in vivo tumor models, respectively. Crucially, in the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41% increase in survival (p ≤ 0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL exhibited significant potential as a targeting agent for malignant brain tumors. Copyright © 2012 UICC.

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

PubMed

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

2018-05-08

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

ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

PubMed Central

Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

2017-01-01

Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

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

PubMed

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

2012-12-11

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

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

NASA Astrophysics Data System (ADS)

Stock, Karl; Hibst, Raimund; Keller, Ulrich

1997-12-01

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

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

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

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

2014-12-07

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

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

PubMed

Fregno, Ilaria; Molinari, Maurizio

2018-01-01

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

Cell-specific Labeling Enzymes for Analysis of Cell–Cell Communication in Continuous Co-culture*

PubMed Central

Tape, Christopher J.; Norrie, Ida C.; Worboys, Jonathan D.; Lim, Lindsay; Lauffenburger, Douglas A.; Jørgensen, Claus

2014-01-01

We report the orthologous screening, engineering, and optimization of amino acid conversion enzymes for cell-specific proteomic labeling. Intracellular endoplasmic-reticulum-anchored Mycobacterium tuberculosis diaminopimelate decarboxylase (DDCM.tub-KDEL) confers cell-specific meso-2,6-diaminopimelate-dependent proliferation to multiple eukaryotic cell types. Optimized lysine racemase (LyrM37-KDEL) supports D-lysine specific proliferation and efficient cell-specific isotopic labeling. When ectopically expressed in discrete cell types, these enzymes confer 90% cell-specific isotopic labeling efficiency after 10 days of co-culture. Moreover, DDCM.tub-KDEL and LyrM37-KDEL facilitate equally high cell-specific labeling fidelity without daily media exchange. Consequently, the reported novel enzyme pairing can be used to study cell-specific signaling in uninterrupted, continuous co-cultures. Demonstrating the importance of increased labeling stability for addressing novel biological questions, we compare the cell-specific phosphoproteome of fibroblasts in direct co-culture with epithelial tumor cells in both interrupted (daily media exchange) and continuous (no media exchange) co-cultures. This analysis identified multiple cell-specific phosphorylation sites specifically regulated in the continuous co-culture. Given their applicability to multiple cell types, continuous co-culture labeling fidelity, and suitability for long-term cell–cell phospho-signaling experiments, we propose DDCM.tub-KDEL and LyrM37-KDEL as excellent enzymes for cell-specific labeling with amino acid precursors. PMID:24820872

DEFECTIVE TRAFFICKING OF CONE PHOTORECEPTOR CNG CHANNELS INDUCES THE UNFOLDED PROTEIN RESPONSE AND ER STRESS-ASSOCIATED CELL DEATH

PubMed Central

Duricka, Deborah L.; Brown, R. Lane; Varnum, Michael D.

2011-01-01

SYNOPSIS Mutations that perturb the function of photoreceptor cyclic nucleotide-gated (CNG) channels are associated with several human retinal disorders, but the molecular and cellular mechanisms leading to photoreceptor dysfunction and degeneration remain unclear. Many loss-of-function mutations result in intracellular accumulation of CNG channel subunits. Accumulation of proteins in the endoplasmic reticulum (ER) is known to cause ER stress and trigger the unfolded protein response (UPR), an evolutionarily conserved cellular program that results in either adaptation via increased protein processing capacity or apoptotic cell death. We hypothesize that defective trafficking of cone photoreceptor CNG channels can induce UPR-mediated cell death. To test this idea, CNGA3 subunits bearing the R563H and Q655X mutations were expressed in photoreceptor-derived 661W cells with CNGB3 subunits. Compared to wild type, R563H and Q655X subunits displayed altered degradation rates and/or were retained in the ER. ER retention was associated with increased expression of UPR-related markers of ER stress and with decreased cell viability. Chemical and pharmacological chaperones (TUDCA, 4PBA, and the cGMP analog CPT-cGMP) differentially reduced degradation and/or promoted plasma-membrane localization of defective subunits. Improved subunit maturation was concordant with reduced expression of ER stress markers and improved viability of cells expressing localization-defective channels. These results indicate that ER stress can arise from expression of localization defective CNG channels, and may represent a contributing factor for photoreceptor degeneration. PMID:21992067

Defective trafficking of cone photoreceptor CNG channels induces the unfolded protein response and ER-stress-associated cell death.

PubMed

Duricka, Deborah L; Brown, R Lane; Varnum, Michael D

2012-01-15

Mutations that perturb the function of photoreceptor CNG (cyclic nucleotide-gated) channels are associated with several human retinal disorders, but the molecular and cellular mechanisms leading to photoreceptor dysfunction and degeneration remain unclear. Many loss-of-function mutations result in intracellular accumulation of CNG channel subunits. Accumulation of proteins in the ER (endoplasmic reticulum) is known to cause ER stress and trigger the UPR (unfolded protein response), an evolutionarily conserved cellular programme that results in either adaptation via increased protein processing capacity or apoptotic cell death. We hypothesize that defective trafficking of cone photoreceptor CNG channels can induce UPR-mediated cell death. To test this idea, CNGA3 subunits bearing the R563H and Q655X mutations were expressed in photoreceptor-derived 661W cells with CNGB3 subunits. Compared with wild-type, R563H and Q655X subunits displayed altered degradation rates and/or were retained in the ER. ER retention was associated with increased expression of UPR-related markers of ER stress and with decreased cell viability. Chemical and pharmacological chaperones {TUDCA (tauroursodeoxycholate sodium salt), 4-PBA (sodium 4-phenylbutyrate) and the cGMP analogue CPT-cGMP [8-(4-chlorophenylthio)-cGMP]} differentially reduced degradation and/or promoted plasma-membrane localization of defective subunits. Improved subunit maturation was concordant with reduced expression of ER-stress markers and improved viability of cells expressing localization-defective channels. These results indicate that ER stress can arise from expression of localization-defective CNG channels, and may represent a contributing factor for photoreceptor degeneration.

Identification of ER proteins involved in the functional organisation of the early secretory pathway in Drosophila cells by a targeted RNAi screen.

PubMed

Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

2011-02-23

In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for "more and smaller Golgi") upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2015-08-01

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

Identification of ER Proteins Involved in the Functional Organisation of the Early Secretory Pathway in Drosophila Cells by a Targeted RNAi Screen

PubMed Central

Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

2011-01-01

Background In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. Results To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for “more and smaller Golgi”) upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. Conclusions This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation. PMID:21383842

YAG:Er3+, CaF2:Er3+, and Er2O3 Emission Spectra Under Laser and Laser Thermal Excitation

NASA Astrophysics Data System (ADS)

Marchenko, V. M.

2018-05-01

Experimental luminescence and selective-emission (SE) spectra of YAG:Er3+ (10 at.%) and CaF2:Er3+ (1 at.%) single crystals and Er2O3 polycrystal under laser and laser thermal excitation of the Er3+-ion multiplets are compared. Luminescence spectra under resonant excitation are determined by multiplet population relaxation with the corresponding radiative and nonradiative probabilities. The form of the SE spectra is determined by the thermal population of the multiplets and the probabilities of only radiative transitions. The SE band at 800 nm (4I9/2 → 4I15/2) is an indicator of high-temperature thermal emission of Er3+ ions. The absence of this band in luminescence spectra is explained by the short lifetime of the τ(4I9/2) level of 53 ns at T = 300 K.

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

PubMed

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

2017-12-01

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

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

Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled alpha-subunits.

PubMed

Valkova, Christina; Albrizio, Marina; Röder, Ira V; Schwake, Michael; Betto, Romeo; Rudolf, Rüdiger; Kaether, Christoph

2011-01-11

The nicotinic acetylcholine receptor of skeletal muscle is composed of five subunits that are assembled in a stepwise manner. Quality control mechanisms ensure that only fully assembled receptors reach the cell surface. Here, we show that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled acetylcholine receptor α-subunits escape from the ER and are transported to the plasma membrane and lysosomes, where they are degraded. As a result, the amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1 knockdown and genetic inactivation of one Rer1 allele lead to significantly smaller neuromuscular junctions in mice. Our data show that Rer1 is a functionally important unique factor that controls surface expression of muscle acetylcholine receptors by localizing unassembled α-subunits to the early secretory pathway.

Exciting transition metal doped dilute magnetic thin films: MgO:Er and ZnO:Er

NASA Astrophysics Data System (ADS)

Ćakıcı, T.; Sarıtaş, S.; Muǧlu, G. Merhan; Yıldırım, M.

2017-02-01

Erbium doped MgO and doped ZnO thin films have reasonably important properties applications in spintronic devices. These films were synthesized on glass substrates by Chemical Spray Pyrolysis (CSP) method. In the literature there has been almost no report on preparation of MgO:Er dilute magnetic thin films by means of CSP. Because doped thin films show different magnetic behaviors, depending upon the type of magnetic material ions, concentration of them, synthesis route and experimental conditions, synthesized MgO:Er and ZnO:Er films were compared to thin film properties. Optical analyses of the synthesized thin films were examined spectral absorption and transmittance measurements by UV-Vis double beam spectrophotometer technique. Structural analysis of the thin films was examined by using XRD, Raman Analysis, FE-SEM, EDX and AFM techniques. Also, magnetic properties of the MgO:Er and ZnO:Er films were investigated by vibrating sample magnetometer (VSM) which show that diamagnetic behavior of the MgO:Er thin film and ferromagnetic (FM) behavior of the ZnO:Er film were is formed.

The role of the AR/ER ratio in ER-positive breast cancer patients.

PubMed

Rangel, Nelson; Rondon-Lagos, Milena; Annaratone, Laura; Osella-Abate, Simona; Metovic, Jasna; Mano, Maria Piera; Bertero, Luca; Cassoni, Paola; Sapino, Anna; Castellano, Isabella

2018-03-01

The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both P  ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours. © 2018 Society for Endocrinology.

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

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

PubMed

Shaheen, Alaa

2018-05-05

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

Retention of a Bean Phaseolin/Maize γ-Zein Fusion in the Endoplasmic Reticulum Depends on Disulfide Bond Formation[W

PubMed Central

Pompa, Andrea; Vitale, Alessandro

2006-01-01

Most seed storage proteins of the prolamin class accumulate in the endoplasmic reticulum (ER) as large insoluble polymers termed protein bodies (PBs), through mechanisms that are still poorly understood. We previously showed that a fusion between the Phaseolus vulgaris vacuolar storage protein phaseolin and the N-terminal half of the Zea mays prolamin γ-zein forms ER-located PBs. Zeolin has 6 Cys residues and, like γ-zein with 15 residues, is insoluble unless reduced. The contribution of disulfide bonds to zeolin destiny was determined by studying in vivo the effects of 2-mercaptoethanol (2-ME) and by zeolin mutagenesis. We show that in tobacco (Nicotiana tabacum) protoplasts, 2-ME enhances interactions of newly synthesized proteins with the ER chaperone BiP and inhibits the secretory traffic of soluble proteins with or without disulfide bonds. In spite of this general inhibition, 2-ME enhances the solubility of zeolin and relieves its retention in the ER, resulting in increased zeolin traffic. Consistently, mutated zeolin unable to form disulfide bonds is soluble and efficiently enters the secretory traffic without 2-ME treatment. We conclude that disulfide bonds that lead to insolubilization are a determinant for PB-mediated protein accumulation in the ER. PMID:17041149

Production of cecropin A antimicrobial peptide in rice seed endosperm

PubMed Central

2014-01-01

Background Cecropin A is a natural antimicrobial peptide that exhibits rapid, potent and long-lasting lytic activity against a broad spectrum of pathogens, thus having great biotechnological potential. Here, we report a system for producing bioactive cecropin A in rice seeds. Results Transgenic rice plants expressing a codon-optimized synthetic cecropin A gene drived by an endosperm-specific promoter, either the glutelin B1 or glutelin B4 promoter, were generated. The signal peptide sequence from either the glutelin B1 or the glutelin B4 were N-terminally fused to the coding sequence of the cecropin A. We also studied whether the presence of the KDEL endoplasmic reticulum retention signal at the C-terminal has an effect on cecropin A subcellular localization and accumulation. The transgenic rice plants showed stable transgene integration and inheritance. We show that cecropin A accumulates in protein storage bodies in the rice endosperm, particularly in type II protein bodies, supporting that the glutelin N-terminal signal peptides play a crucial role in directing the cecropin A to this organelle, independently of being tagged with the KDEL endoplasmic reticulum retention signal. The production of cecropin A in transgenic rice seeds did not affect seed viability or seedling growth. Furthermore, transgenic cecropin A seeds exhibited resistance to infection by fungal and bacterial pathogens (Fusarium verticillioides and Dickeya dadantii, respectively) indicating that the in planta-produced cecropin A is biologically active. Conclusions Rice seeds can sustain bioactive cecropin A production and accumulation in protein bodies. The system might benefit the production of this antimicrobial agent for subsequent applications in crop protection and food preservation. PMID:24755305

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

Shear mode ER transfer function for robotic applications

NASA Astrophysics Data System (ADS)

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

2005-06-01

Electro-rheological (ER) fluids are becoming popular in modern industrial applications. The advantage of employing ER devices is due to the ease of energizing the ER fluids at fast speeds of response. One innovation in ER applications could be in the positioning control of the robotic arm using an ER clutch. In order to actuate the manipulator, the ER output torque response is required. However, the behaviour of this ER torque response at different input conditions is not clearly understood. Therefore, in this paper, a sample study of the ER output torque is conducted. The ER output torque responses at different input parameters are studied carefully for the establishment of an appropriate ER transfer function in shear mode. This transfer function will serve as an important feature in future ER-actuated robot arm's control process.

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

PubMed Central

Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

2017-01-01

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

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

NASA Astrophysics Data System (ADS)

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

1986-05-01

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

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

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

Leanos-Castaneda, Olga; Kraak, Glen van der

2007-10-15

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

Identification of the heat shock protein 70 (HLHsp70) in Haemaphysalis longicornis.

PubMed

Tian, Zhancheng; Liu, Guangyuan; Zhang, Liyan; Yin, Hong; Wang, Hui; Xie, Junren; Zhang, Ping; Luo, Jin

2011-09-27

A Haemaphysalis longicornis heat shock protein 70 (HLHsp70) was identified from a cDNA library synthesized from tick eggs. The HLHsp70 cDNA is 2311 bp in length and encodes 661 amino acid residues with the predicted molecular weight of 72.5 kDa and an isoelectronic point (pI) of 5.2. It also contains the highly conserved functional motifs of the Hsp70 family and a specific endoplasmic reticulum (ER) retention signal "KDEL" that is common among ER-localized proteins. The HLHsp70 exhibits 90% amino acid identity to the putative Hsp70 of Ixodes scapularis, and 85% to Gallus gallus 78 kDa glucose-regulated protein precursor. Real time RT-PCR analysis showed that the expression levels of the Hsp70 in ovaries and salivary glands were significantly higher than in other tested tissues in partially fed females. Although the expression level of the HLHsp70 was constantly low in unfed ticks, it was significantly induced by blood-feeding. Further, the expression was positively correlated to the temperature (4-37°C, tested). Western blot analysis showed that the rabbit antiserum against the recombinant HLHsp70 protein (rHLHSP70) recognized bands of approximately 100, 72, and 28 kDa from egg lysates, as well as a 72kDa fragment in protein extracts from partially fed larvae. Immunization of rabbits with the rHLHSP70 did not result in a statistically significant reduction of female tick engorgement and oviposition. These results suggest that although HLHSP70 plays a role in the physiological activities of ticks, as a constitutive protein it was not suitable for selection as a candidate vaccine antigen against ticks. Copyright © 2011 Elsevier B.V. All rights reserved.

Investigating the evolution of local structure around Er and Yb in ZnO:Er and ZnO:Er, Yb on annealing using X-ray absorption spectroscopy

NASA Astrophysics Data System (ADS)

Anjana, R.; Jayaraj, M. K.; Yadav, A. K.; Jha, S. N.; Bhattacharyya, D.

2018-04-01

The local structure around Er and Yb centre in ZnO favouring upconversion luminescence was studied using EXAFS (Extended X-ray absorption fine structure spectroscopy). Due to the ionic radii difference between Zn and Er, Yb ions, the dopants cannot replace Zn in the ZnO lattice properly. Er2O3 and Yb2O3 impurity phases are formed at the grain boundaries of ZnO. It is found that the local structure around the Er centre in ZnO is modified on annealing in air. The symmetry around both erbium and ytterbium reduces with increase in annealing temperature. Symmetry reduction will favour the intra-4f transition and the energy transitions causing upconversion luminescence. By fitting the EXAFS data with theoretically simulated data, it is found that the Er centre forms a local structure similar to C4ν symmetry which is a distorted octahedron. On annealing the sample to 1200 °C, all the erbium centres are transformed to C4ν symmetry causing enhanced upconversion emission. Yb centre has also been modified on annealing. The decrease in co-ordination number with annealing temperature will decrease the symmetry and increase the near infrared absorption cross section. The decrease in symmetry around both the erbium and ytterbium centre and formation of C4ν symmetry around Er centre is the reason behind the activation of upconversion luminescence with high temperature annealing in both Er doped and Er, Yb co-doped ZnO samples. The study will be useful for the synthesis of high efficiency upconversion materials.

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

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

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

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

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

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

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

2008-07-15

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

Excited-state absorption in Er: BaY2F8 and Cs3Er2Br9 and comparison with Er: LiYF4

NASA Astrophysics Data System (ADS)

Pollnau, M.; Lüthy, W.; Weber, H. P.; Krämer, K.; Güdel, H. U.; McFarlane, R. A.

1996-04-01

The influence of Excited-State Absorption (ESA) on the green laser transition and the overlap of Ground-State Absorption (GSA) and ESA for 970 nm upconversion pumping in erbium is investigated in Er3+ : BaY2F8 and Cs3Er2Br9. Results are compared to Er3+ : LiYF4. In Er3+: BaY2F8, a good overlap between GSA and ESA is found at 969 nm in one polarization direction. The emission cross section at 550 nm is a factor of two smaller than in LiYF4. In Cs3Er2Br9, the smaller Stark splitting of the levels shifts the wavelengths of the green emission and ESA from4 I 1 3/2 off resonance. It enhances, however, ground-state reabsorption. The emission cross section at 550 nm is comparable to LiYF4. Upconversion leads to significant green fluorescence from2 H 9/2. A significant population of the4 I 11/2 level and ESA at 970 nm are not present under 800 nm pumping.

ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

PubMed

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

2018-04-22

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

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

PubMed Central

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

2014-01-01

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

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.

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

Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

PubMed

Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

2013-01-01

The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

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

78 FR 40757 - Prospective Grant of Start-Up Exclusive Commercialization License: The Development of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... Pseudomonas Exotoxin A (cpIL4-PE38KDEL) for the Treatment of Cancers and Urological Disorders AGENCY: National... urological disorders that express the IL4 receptor on their cell surface by using cpIL4-PE38KDEL. DATES: Only... contains a circularly permuted interleukin 4 (cpIL4) ligand, which binds to the IL4 receptor. The IL4...

FIRE_ACE_ER2_MAS

Atmospheric Science Data Center

2017-04-26

... Moderate Resolution Imaging Spectrometer (MODIS) Airborne Simulator (MAS) Data Project Title:  MAS ... IDL Code ER2 Flight Tracks Related Data:  MAS Additional Info:  ER-2 MODIS Airborne Simulator (MAS) Image Gallery:  ...

Adiponectin improves insulin sensitivity via activation of autophagic flux.

PubMed

Ahlstrom, Penny; Rai, Esther; Chakma, Suharto; Cho, Hee Ho; Rengasamy, Palanivel; Sweeney, Gary

2017-11-01

Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance. © 2017 Society for Endocrinology.

Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines.

PubMed

Flocke, Lea S; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K

2016-06-01

Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action.

Raman Spectrum of Er-Y-codoped ZrO2 and Fluorescence Properties of Er3+

NASA Astrophysics Data System (ADS)

He, Jun; Luo, Meng-fei; Jin, Ling-yun; He, Mai; Fang, Ping; Xie, Yun-long

2007-02-01

Er-Y-codoped ZrO2 mixed oxides with monoclinic, tetragonal and cubic structures were prepared by a sol-gel method. The crystal structure of ZrO2 matrix and the effect of the ZrO2 phases on the fluorescence properties of Er3+ were studied using Raman spectroscopy. The results indicated that the fluorescence properties of Er3+ depend on its local ZrO2 crystal structures. As ZrO2 matrix transferred from monoclinic to tetragonal and cubic phase, the Raman and fluorescence bands of Er3+ decreased in intensities and tended to form a single peak. With 632.8 nm excitation, the bands between 640 and 680 nm were attributed to the fluorescence of Er3+ in the ZrO2 environment. However, only the fluorescence was observed and no Raman spectra were seen under 514.5 nm excitation, while only Raman spectra were observed under 325 nm excitation. UV Raman spectroscopy was found to be more sensitive in the surface region while the information provided by XRD mainly came from the bulk. The phase with lower symmetry forms more easily on the surface than in the bulk.

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

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

Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki

2011-02-18

Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. Themore » overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.« less

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

FIRE_AX_ER2_MAS

Atmospheric Science Data Center

2015-11-24

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

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.

PubMed

Bao, Xuhui; Chandramohan, Vidyalakshmi; Reynolds, Randall P; Norton, John N; Wetsel, William C; Rodriguiz, Ramona M; Aryal, Dipendra K; McLendon, Roger E; Levin, Edward D; Petry, Neil A; Zalutsky, Michael R; Burnett, Bruce K; Kuan, Chien-Tsun; Pastan, Ira H; Bigner, Darell D

2016-04-01

D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2C7-IT to support an initial Food and Drug Administration Investigational New Drug application. After the optimization of the formulation and administration, two cohorts (an acute and chronic cohort necropsied on study days 5 and 34) of Sprague-Dawley (SD) rats (four groups of 5 males and 5 females) were infused with the D2C7-IT formulation at total doses of 0, 0.05, 0.1, 0.4 μg (the acute cohort) and 0, 0.05, 0.1, 0.35 μg (the chronic cohort) for approximately 72 h by intracerebral convection-enhanced delivery using osmotic pumps. Mortality was observed in the 0.40 μg (5/10 rats) and 0.35 μg (4/10 rats) high-dose groups of each cohort. Body weight loss and abnormal behavior were only revealed in the rats treated with high doses of D2C7-IT. No dose-related effects were observed in clinical laboratory tests in either cohort. A gross pathologic examination of systemic tissues from the high-dose and control groups in both cohorts exhibited no dose-related or drug-related pathologic findings. Brain histopathology revealed the frequent occurrence of dose-related encephalomalacia, edema, and demyelination in the high-dose groups of both cohorts. In this study, the maximum tolerated dose of D2C7-IT was determined to be between 0.10 and 0.35 μg, and the no-observed-adverse-effect-level was 0.05 μg in SD rats. Both parameters were utilized to design the Phase I/II D2C7-IT clinical trial.

Intrinsic attenuation of post-irradiation calcium and ER stress imparts significant radioprotection to lepidopteran insect cells.

PubMed

Guleria, Ayushi; Thukral, Neha; Chandna, Sudhir

2018-04-15

Sf9 lepidopteran insect cells are 100-200 times more radioresistant than mammalian cells. This distinctive feature thus makes them suitable for studies exploring radioprotective molecular mechanisms. It has been established from previous studies of our group that downstream mitochondrial apoptotic signaling pathways in Sf9 cells are quite similar to mammalian cells, implicating the upstream signaling pathways in their extensive radioresistance. In the present study, intracellular and mitochondrial calcium levels remained unaltered in Sf9 cells in response to radiation, in sharp contrast to human (HEK293T) cells. The isolated mitochondria from Sf9 cells exhibited nearly 1.5 times greater calcium retention capacity than mammalian cells, highlighting their inherent stress resilience. Importantly, UPR/ER stress marker proteins (p-eIF2α, GRP4 and SERCA) remained unaltered by radiation and suggested highly attenuated ER and calcium stress. Lack of SERCA induction further corroborates the lack of radiation-induced calcium mobilization in these cells. The expression of CaMKII, an important effector molecule of calcium signaling, did not alter in response to radiation. Inhibiting CaMKII by KN-93 or suppressing CaM by siRNA failed to alter Sf9 cells response to radiation and suggests CaM-CaMKII independent radiation signaling. Therefore, this study suggests that attenuated calcium signaling/ER stress is an important determinant of lepidopteran cell radioresistance. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

PubMed

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

2006-12-01

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

Electroreduction of Er 3+ in nonaqueous solvents

DOE PAGES

Small, Leo J.; Sears, Jeremiah M.; Lambert, Timothy N.; ...

2016-09-15

Here, the electroreduction of Er 3+ in propylene carbonate, N,N-dimethylformamide, or a variety of quaternary ammonium ionic liquids (ILs) was investigated using [Er(OTf) 3] and [Er(NTf 2) 3]. Systematic variation of the ILs' cation and anion, Er 3+ salt, and electrode material revealed a disparity in electrochemical interactions not previously seen. For most ILs at a platinum electrode, cyclic voltammetry exhibits irreversible interactions between Er 3+ salts and the electrode at potentials significantly less than the theoretical reduction potential for Er 3+. Throughout all solvent–salt systems tested, a deposit could be formed on the electrode, though obtaining a high purity,more » crystalline Er 0 deposit is challenging due to the extreme reactivity of the deposit and resulting chemical interactions, often resulting in the formation of a complex, amorphous solid–electrolyte interface that slowed deposition rates. Comparison of platinum, gold, nickel, and glassy carbon (GC) working electrodes revealed oxidation processes unique to the platinum surface. While no appreciable reduction current was observed on GC at the potentials investigated, deposits were seen on platinum, gold, and nickel electrodes.« less

Diffusion and retention are major determinants of protein targeting to the inner nuclear membrane

PubMed Central

Ungricht, Rosemarie; Klann, Michael; Horvath, Peter

2015-01-01

Newly synthesized membrane proteins are constantly sorted from the endoplasmic reticulum (ER) to various membranous compartments. How proteins specifically enrich at the inner nuclear membrane (INM) is not well understood. We have established a visual in vitro assay to measure kinetics and investigate requirements of protein targeting to the INM. Using human LBR, SUN2, and LAP2β as model substrates, we show that INM targeting is energy-dependent but distinct from import of soluble cargo. Accumulation of proteins at the INM relies on both a highly interconnected ER network, which is affected by energy depletion, and an efficient immobilization step at the INM. Nucleoporin depletions suggest that translocation through nuclear pore complexes (NPCs) is rate-limiting and restricted by the central NPC scaffold. Our experimental data combined with mathematical modeling support a diffusion-retention–based mechanism of INM targeting. We experimentally confirmed the sufficiency of diffusion and retention using an artificial reporter lacking natural sorting signals that recapitulates the energy dependence of the process in vivo. PMID:26056139

Hard tooth tissue removal by short and long Er:YAG or Er,Cr:YSGG mid-infrared laser radiation

NASA Astrophysics Data System (ADS)

Jelínková, H.; Dostálová, T.; Remeš, M.; Šulc, J.; Němec, M.; Fibrich, M.

2017-02-01

Hard dental tissue removal by laser radiation is an alternative treatment to conventional dental-drilling procedures. The advantages of this therapy are fast and localized treatment of hard dental tissue and painlessness. The most effective systems for those purposes are Er-lasers generating radiation at wavelengths of around 3 μm. The aim of this study was qualitative and quantitative examination of human dentin and ivory tissue removal by pulsed free-running (FR) and Q-switched (QSW) Er:YAG and Er,Cr:YSGG laser radiations. From the obtained results it follows that generally Er:YAG laser has lower threshold for the tissue removal in both FR and QSW regimes. Furthermore, the FR Er:YAG and Er,Cr:YSGG radiation can be effective for both dentin and ivory ablation and can prepare smooth cavities without side effects. The QSW regime is useful preferably for precise ablation of a starting tooth defect and for the part of the tooth very close to the gum. This regime is excellent for micro-preparation or for tooth treatment of children.

An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

PubMed

Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

2014-01-16

Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

ORTHODONTIC RETENTION. Studies of retention capacity, cost-effectiveness and long-term stability.

PubMed

Tynelius, Gudrun Edman

2014-01-01

Retention strategies, cost-effectiveness and long-term stability of treatment outcome are essential aspects of orthodontic treatment planning. The overall aim of this thesis was to compare and evaluate three different retention strategies, with special reference to short- and long-term clinical stability and cost-effectiveness. The approach was evidence-based, hence randomized controlled methodology was used in order to generate high levels of evidence. This thesis is based on four studies: Papers I and II are based on randomized controlled trials, evaluating the stability of treatment outcome after one and two years of retention, using three different retention strategies: a maxillary vacuum-formed retainer combined with a mandibular canine-to-canine retainer; a maxillary vacuum-formed retainer combined with stripping of the mandibular anterior teeth and a prefabricated positioner. Paper III presents a cost-minimization analysis of two years of retention treatment. Paper IV is based on a randomized controlled trial documenting the results five years post-retention. The following conclusions were drawn: Papers I and II. From a clinical perspective, asssessment after one year of retention disclosed that the three retention methods were successful in retaining the orthodontic treatment results. After two years of retention, all three retention methods were equally effective in controlling relapse at a clinically acceptable level. Most of the relapse occurred during the first year of retention; only minor or negligible changes were found during the second year. The subjects were grouped according to the level of compliance (excellent or good). After two years of retention there was a negative correlation between growth in body height and relapse of mandibular LII in the group of subjects with excellent compliance. The group with good compliance showed a positive correlation (Paper II, Figure 3). After two years of retention, growth in body height, initial crowding and

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

PubMed

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

2014-03-01

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

Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma

PubMed Central

Zeelenberg, Ingrid S.; Stalle, Lisette Ruuls-Van; Roos, Ed

2001-01-01

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor. PMID:11457880

Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma.

PubMed

Zeelenberg, I S; Ruuls-Van Stalle, L; Roos, E

2001-07-01

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.

Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

PubMed

Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

2010-04-01

Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

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

Factors That Influence Enrolment and Retention in Ghana’ National Health Insurance Scheme

PubMed Central

Millicent Kotoh, Agnes; Aryeetey, Genevieve Cecilia; der Geest, Sjaak Van

2018-01-01

Background: The government of Ghana introduced the National Health Insurance Scheme (NHIS) in 2004 with the goal of achieving universal coverage within 5 years. Evidence, however, shows that expanding NHIS coverage and especially retaining members have remained a challenge. A multilevel perspective was employed as a conceptual framework and methodological tool to examine why enrolment and retention in the NHIS remains low. Methods: A household survey was conducted after 20 months educational and promotional activities aimed at improving enrolment and retention rates in 15 communities in the Central and Eastern Regions (ERs) of Ghana. Observation, indepth interviews and informal conversations were used to collect qualitative data. Forty key informants (community members, health providers and district health insurance schemes’ [DHISs] staff) purposely selected from two casestudy communities in the Central Region (CR) were interviewed. Several community members, health providers and DHISs’ staff were also engaged in informal conversations in the other five communities in the region. Also, four staff of the Ministry of Health (MoH), Ghana Health Service (GHS) and National Health Insurance Authority (NHIA) were engaged in in-depth interviews. Descriptive statistics was used to analyse quantitative data. Qualitative data was analysed using thematic content analysis. Results: The results show that factors that influence enrolment and retention in the NHIS are multi-dimensional and cut across all stakeholders. People enrolled and renewed their membership because of NHIS’ benefits and health providers’ positive behaviour. Barriers to enrolment and retention included: poverty, traditional risk-sharing arrangements influence people to enrol or renew their membership only when they need healthcare, dissatisfaction about health providers’ behaviour and service delivery challenges. Conclusion: Given the multi-dimensional nature of barriers to enrolment and retention

Generation of a transgenic rice seed-based edible vaccine against house dust mite allergy.

PubMed

Yang, Lijun; Kajiura, Hiroyuki; Suzuki, Kazuya; Hirose, Sakiko; Fujiyama, Kazuhito; Takaiwa, Fumio

2008-01-11

As an alternative approach to conventional allergen-specific immunotherapy, transgenic rice seed expressing a major house dust mite (HDM) allergen, Der p 1, was developed as an edible vaccine. The C-terminal KDEL-tagged Der p 1 allergen specifically accumulated in seed endosperm tissue under the control of the endosperm-specific GluB1 promoter. Der p 1 reached a maximum concentration of 58 microg/grain and was deposited in the endoplasmic reticulum (ER)-derived protein body I (PB-I). Plant-derived Der p 1 was posttranslationally modified with high-mannose-type glycan structures. Glycosylated Der p 1 displayed reduced IgE binding capacity in comparison with its unglycosylated counterpart in vitro. Our results indicate that transgenic Der p 1 rice seeds are a safe, potential oral delivery vaccine for the treatment of HDM allergy.

Radioimmunotoxin Therapy of Experimental Colon and Ovarian Cancer

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

Buchsbaum, Donald J.; Vallera, Daniel A.

2006-02-09

Cam was mixed with the EpCam sFv that was synthesized without any toxin attached. The proliferation studies showed that EpCam sFv was able to block the killing of the EpCam expressing cells by DTEpCam. An irrelevant control protein, 1D10Fc was unable to block. Together, these studies indicated that EpCam was exquisitely selective. In order to produce an IT of even greater potency, we used a toxin containing the Golgi retention sequence KDEL. The same EpCam sFv was spliced to truncated PE containing the terminal KDEL sequence. The addition of KDEL enhanced the potency of the EpCam sFv IT at least 6 logs or 1000-fold with an IC50 of 2 to 7 x 10-8 nM. This conjugate was also shown to be highly selective. Taken together, all of these studies indicate that in vitro experiments have shown that we have a highly potent IT that selectively kills colon cancer cells. The next step was to show that the EpCam IT had the ability to inhibit the growth of flank tumors in vivo in nude mice. The same human colon tumor cells, HT29 used in the in vitro studies were injected into the flank of nude mice. Tumor cells were injected into groups of mice and when tumors reached the size of 0.5 cm3, we injected our best-performing EpCam IT called EpCamKDEL intratumorally. There was a significant drop in tumor size indicating that this agent was very effective against human colon cancer. Since the EpCamKDEL was injected intratumorally, it did not have to travel through the systemic circulation to find its target. Our next step will be to inject EpCamKDEL intravenously into mice with flank tumors to determine if EpCamKDEL has the ability to migrate to the tumor systemically. The next step was to radiolabel EpCamKDEL to see whether it could serve as an RIT. We radiolabeled EpCam with 111In as a surrogate for 90Y and then incubated it with HT29. The labeling efficiency was over 90% indicating that a high percentage of the protein molecules could be readily radiolabeled. However, the immunoreactivity was

Enhancement of endoplasmic reticulum (ER) degradation of misfolded Null Hong Kong alpha1-antitrypsin by human ER mannosidase I.

PubMed

Hosokawa, Nobuko; Tremblay, Linda O; You, Zhipeng; Herscovics, Annette; Wada, Ikuo; Nagata, Kazuhiro

2003-07-11

Misfolded glycoproteins synthesized in the endoplasmic reticulum (ER) are degraded by cytoplasmic proteasomes, a mechanism known as ERAD (ER-associated degradation). In the present study, we demonstrate that ERAD of the misfolded genetic variant-null Hong Kong alpha1-antitrypsin is enhanced by overexpression of the ER processing alpha1,2-mannosidase (ER ManI) in HEK 293 cells, indicating the importance of ER ManI in glycoprotein quality control. We showed previously that EDEM, an enzymatically inactive mannosidase homolog, interacts with misfolded alpha1-antitrypsin and accelerates its degradation (Hosokawa, N., Wada, I., Hasegawa, K., Yorihuzi, T., Tremblay, L. O., Herscovics, A., and Nagata, K. (2001) EMBO Rep. 2, 415-422). Herein we demonstrate a combined effect of ER ManI and EDEM on ERAD of misfolded alpha1-antitrypsin. We also show that misfolded alpha1-antitrypsin NHK contains labeled Glc1Man9GlcNAc and Man5-9GlcNAc released by endo-beta-N-acetylglucosaminidase H in pulse-chase experiments with [2-3H]mannose. Overexpression of ER ManI greatly increases the formation of Man8GlcNAc, induces the formation of Glc1Man8GlcNAc and increases trimming to Man5-7GlcNAc. We propose a model whereby the misfolded glycoprotein interacts with ER ManI and with EDEM, before being recognized by downstream ERAD components. This detailed characterization of oligosaccharides associated with a misfolded glycoprotein raises the possibility that the carbohydrate recognition determinant triggering ERAD may not be restricted to Man8GlcNAc2 isomer B as previous studies have suggested.

Periodontal disease level-butyric acid amounts locally administered in the rat gingival mucosa induce ER stress in the systemic blood.

PubMed

Cueno, Marni E; Saito, Yuko; Ochiai, Kuniyasu

2016-05-01

Periodontal diseases have long been postulated to contribute to systemic diseases and, likewise, it has been proposed that periodontal disease treatment may ameliorate certain systemic diseases. Short-chain fatty acids (SCFA) are major secondary metabolites produced by oral anaerobic bacteria and, among the SCFAs, butyric acid (BA) in high amounts contribute to periodontal disease development. Periodontal disease level-butyric acid (PDL-BA) is found among patients suffering from periodontal disease and has previously shown to induce oxidative stress, whereas, oxidative stress is correlated to endoplasmic reticulum (ER) stress. This would imply that PDL-BA may likewise stimulate ER stress, however, this was never elucidated. A better understanding of the correlation between PDL-BA and systemic ER stress stimulation could shed light on the possible systemic effects of PDL-BA-related periodontal diseases. Here, PDL-BA was injected into the gingival mucosa and the systemic blood obtained from the rat jugular was collected at 0, 15, 60, and 180 min post-injection. Collected blood samples were purified and only the blood cytosol was used throughout this study. Subsequently, we measured blood cytosolic GADD153, Ca(2+), representative apoptotic and inflammatory caspases, and NF-κB amounts. We found that PDL-BA presence increased blood cytosolic GADD153 and Ca(2+) amounts. Moreover, we observed that blood cytosolic caspases and NF-κB were activated only at 60 and 180 min post-injection in the rat gingival mucosa. This suggests that PDL-BA administered through the gingival mucosa may influence the systemic blood via ER stress stimulation and, moreover, prolonged PDL-BA retention in the gingival mucosa may play a significant role in ER stress-related caspase and NF-κB activation. In a periodontal disease scenario, we propose that PDL-BA-related ER stress stimulation leading to the simultaneous activation of apoptosis and inflammation may contribute to periodontal disease

Prevention of ER-Negative Breast Cancer

PubMed Central

Li, Yuxin

2014-01-01

The successful demonstration that the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of breast cancer has stimulated great interest in using drugs to prevent breast cancer in high-risk women. In addition, recent results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective at preventing breast cancer than are SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many estrogen-receptor (ER)-positive breast cancers, these drugs do not prevent the development of ER-negative breast cancer. Thus, there is an urgent need to identify agents that can prevent ER-negative breast cancer. We have studied the cancer preventative activity of several classes of drugs for their ability to prevent ER-negative breast cancer in preclinical models. Results from these studies demonstrate that rexinoids (analogs of retinoids that bind and activate RXR receptors), tyrosine kinase inhibitors (such as EGFR inhibitors and dual kinase inhibitors that block EGFR and HER2/neu signaling), and cyclo-oxygenase 2 (COX-2) inhibitors all prevent ER-negative breast cancer in transgenic mice that develop ER-negative breast cancer. Other promising agents now under investigation include vitamin D and vitamin D analogs, drugs that activate PPAR-gamma nuclear receptors, and statins. Many of these agents are now being tested in early phase cancer prevention clinical trials to determine whether they will show activity in breast tissue and whether they are safe for use in high-risk women without breast cancer. The current status of these studies will be reviewed. It is anticipated that in the future, drugs that effectively prevent ER-negative breast cancer will be used in combination with hormonal agents such SERMs or aromatase inhibitors to prevent all forms of breast cancer. PMID:19213564

Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.

PubMed

Kanaya, Noriko; Somlo, George; Wu, Jun; Frankel, Paul; Kai, Masaya; Liu, Xueli; Wu, Shang Victoria; Nguyen, Duc; Chan, Nymph; Hsieh, Meng-Yin; Kirschenbaum, Michele; Kruper, Laura; Vito, Courtney; Badie, Behnam; Yim, John H; Yuan, Yuan; Hurria, Arti; Peiguo, Chu; Mortimer, Joanne; Chen, Shiuan

2017-06-01

The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2000-09-01

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

The ERS Research Agency: the beginning.

PubMed

Soriano, Joan B; Paton, James; Martin Burrieza, Fernando; Bill, Werner; Pannetier, Carine; Aliberti, Stefano; Adcock, Ian M; Wagers, Scott; Migliori, Giovanni Battista

2016-04-01

There is at the current time a significant opportunity for the ERS to leverage its experience and reputation as an international umbrella organisation to promote high-quality, multinational respiratory research with the goal of improving the health of respiratory patients. This editorial proposes a model for the role and structure of an ERS Research Agency. It is based upon research, implicit knowledge and explicit feedback from ERS members and selected external individuals and organisations.As with any new endeavour there are challenges and threats. Building a Research Agency will be a major undertaking that will require significant organisational planning, resources, effort and commitment.Organisations with multiple stakeholders tend to have a status quo inertia that has to be overcome for any significant new endeavour. The ERS Research Agency could be an investment in the future of respiratory research.

Fuel nozzle tube retention

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

Cihlar, David William; Melton, Patrick Benedict

A system for retaining a fuel nozzle premix tube includes a retention plate and a premix tube which extends downstream from an outlet of a premix passage defined along an aft side of a fuel plenum body. The premix tube includes an inlet end and a spring support feature which is disposed proximate to the inlet end. The premix tube extends through the retention plate. The spring retention feature is disposed between an aft side of the fuel plenum and the retention plate. The system further includes a spring which extends between the spring retention feature and the retention plate.

Laser performance of in-band pumped Er : LiYF{sub 4} and Er : LiLuF{sub 4} crystals

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

Gorbachenya, K N; Kisel, V E; Yasukevich, A S

2016-02-28

Spectroscopic properties of Er : LiLuF{sub 4} and Er : LiYF{sub 4} crystals in the spectral region near 1.5 μm and the lasing characteristics of these crystals under in-band pumping at a wavelength of 1522 nm are studied. With the Er : LiLuF{sub 4} crystal, the maximum slope efficiency with respect to the absorbed pump power was 44% at a wavelength of 1609 nm. Continuous-wave operation of an inband pumped Er : LiYF{sub 4} laser is obtained for the first time. The output power at a wavelength of 1606 nm was 58 mW with a slope efficiency of 21%. (lasers)

Generation of transgenic wheat (Triticum aestivum L.) accumulating heterologous endo-xylanase or ferulic acid esterase in the endosperm.

PubMed

Harholt, Jesper; Bach, Inga C; Lind-Bouquin, Solveig; Nunan, Kylie J; Madrid, Susan M; Brinch-Pedersen, Henrik; Holm, Preben B; Scheller, Henrik V

2010-04-01

Endo-xylanase (from Bacillus subtilis) or ferulic acid esterase (from Aspergillus niger) were expressed in wheat under the control of the endosperm-specific 1DX5 glutenin promoter. Constructs both with and without the endoplasmic reticulum retention signal (Lys-Asp-Glu-Leu) KDEL were used. Transgenic plants were recovered in all four cases but no qualitative differences could be observed whether KDEL was added or not. Endo-xylanase activity in transgenic grains was increased between two and threefold relative to wild type. The grains were shrivelled and had a 25%-33% decrease in mass. Extensive analysis of the cell walls showed a 10%-15% increase in arabinose to xylose ratio, a 50% increase in the proportion of water-extractable arabinoxylan, and a shift in the MW of the water-extractable arabinoxylan from being mainly larger than 85 kD to being between 2 and 85 kD. Ferulic acid esterase-expressing grains were also shrivelled, and the seed weight was decreased by 20%-50%. No ferulic acid esterase activity could be detected in wild-type grains whereas ferulic acid esterase activity was detected in transgenic lines. The grain cell walls had 15%-40% increase in water-unextractable arabinoxylan and a decrease in monomeric ferulic acid between 13% and 34%. In all the plants, the observed changes are consistent with a plant response that serves to minimize the effect of the heterologously expressed enzymes by increasing arabinoxylan biosynthesis and cross-linking.

Generation of transgenic wheat (Triticum aestivum L.) accumulating heterologous endo-xylanase or ferulic acid esterase in the endosperm

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

Harholt, Jesper; Bach, Inga C; Lind-Bouquin, Solveig

2009-12-08

Endo-xylanase (from Bacillus subtilis) or ferulic acid esterase (from Aspergillus niger) were expressed in wheat under the control of the endosperm specific 1DX5 glutenin promoter. Constructs both with and without the endoplasmic reticulum retention signal KDEL were used. Transgenic plants were recovered in all four cases but no qualitative differences could be observed whether KDEL was added or not. Endo-xylanase activity in transgenic grains was increased between two and three fold relative to wild type. The grains were shriveled and had a 25-33% decrease in mass. Extensive analysis of the cell walls showed a 10-15% increase in arabinose to xylosemore » ratio, a 50% increase in the proportion of water extractable arabinoxylan, and a shift in the MW of the water extractable arabinoxylan from being mainly larger than 85 kD to being between 2 kD and 85 kD. Ferulic acid esterase expressing grains were also shriveled and the seed weight was decreased by 20-50%. No ferulic acid esterase activity could be detected in wild type grains whereas ferulic acid esterase activity was detected in transgenic lines. The grain cell walls had 15-40% increase in water unextractable arabinoxylan and a decrease in monomeric ferulic acid between 13 and 34%. In all the plants the observed changes are consistent with a plant response that serves to minimize the effect of the heterologously expressed enzymes by increasing arabinoxylan biosynthesis and cross-linking.« less

Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

PubMed

Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A

2008-05-01

The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

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

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

Yang, Ping; Fu, Shilong; Cao, Zhifei

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

ER2OWL: Generating OWL Ontology from ER Diagram

NASA Astrophysics Data System (ADS)

Fahad, Muhammad

Ontology is the fundamental part of Semantic Web. The goal of W3C is to bring the web into (its full potential) a semantic web with reusing previous systems and artifacts. Most legacy systems have been documented in structural analysis and structured design (SASD), especially in simple or Extended ER Diagram (ERD). Such systems need up-gradation to become the part of semantic web. In this paper, we present ERD to OWL-DL ontology transformation rules at concrete level. These rules facilitate an easy and understandable transformation from ERD to OWL. The set of rules for transformation is tested on a structured analysis and design example. The framework provides OWL ontology for semantic web fundamental. This framework helps software engineers in upgrading the structured analysis and design artifact ERD, to components of semantic web. Moreover our transformation tool, ER2OWL, reduces the cost and time for building OWL ontologies with the reuse of existing entity relationship models.

Er 3+ Doping conditions of planar porous silicon waveguides

NASA Astrophysics Data System (ADS)

Najar, A.; Lorrain, N.; Ajlani, H.; Charrier, J.; Oueslati, M.; Haji, L.

2009-11-01

EDX and infrared photoluminescence (IR PL) analyses performed on erbium-doped porous silicon waveguides (PSWG) were studied using different doping conditions. Both parameters of the cathodisation electrochemical method used for Er incorporation and parameters of thermal treatments required for Er optical activation were taken into consideration. Firstly, by varying the current density and the time of cathodisation, we have shown that a current density of 0.1 mA/cm 2 for 10 min allows homogeneous Er doping to be achieved throughout the depth of the guiding layer. Then, the PL intensity at 1.53 μm was studied as a function of the oxidation time at 900 °C and Er diffusion temperature for 60 min. Increasing the oxidation time up to 1 h allows PL to be enhanced due to active Si-O-Er complex formation whereas an oxidation time of 2 h induces a decrease in PL because of Er segregation. Moreover, an increase in the diffusion temperature induces an optimal distribution of optically active Si-Er-O complexes inside the crystallites. When the temperature is too high, a PSWG densification and Er segregation occurs inducing a decrease in PL due to energy transfer phenomena.

SR/ER-mitochondrial local communication: Calcium and ROS

PubMed Central

Csordás, György; Hajnóczky, György

2009-01-01

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

MicroRNAs meet calcium: joint venture in ER proteostasis.

PubMed

Finger, Fabian; Hoppe, Thorsten

2014-11-04

The endoplasmic reticulum (ER) is a cellular compartment that has a key function in protein translation and folding. Maintaining its integrity is of fundamental importance for organism's physiology and viability. The dynamic regulation of intraluminal ER Ca(2+) concentration directly influences the activity of ER-resident chaperones and stress response pathways that balance protein load and folding capacity. We review the emerging evidence that microRNAs play important roles in adjusting these processes to frequently changing intracellular and environmental conditions to modify ER Ca(2+) handling and storage and maintain ER homeostasis. Copyright © 2014, American Association for the Advancement of Science.

Optimized transitory ectopic expression of promastigote surface antigen protein in Nicotiana benthamiana, a potential anti-leishmaniasis vaccine candidate.

PubMed

Lacombe, Séverine; Bangratz, Martine; Brizard, Jean-Paul; Petitdidier, Elodie; Pagniez, Julie; Sérémé, Drissa; Lemesre, Jean-Loup; Brugidou, Christophe

2018-01-01

In recent years, plants have been shown to be an efficient alternative expression system for high-value pharmaceuticals such as vaccines. However, constitutive expression of recombinant protein remains uncertain on their level of production and biological activity. To overcome these problems, transitory expression systems have been developed. Here, a series of experiments were performed to determine the most effective conditions to enhance vaccine antigen transient accumulation in Nicotiana benthamiana leaves using the promastigote surface antigen (PSA) from the parasitic protozoan Leishmania infantum. This protein has been previously identified as the major antigen of a licensed canine anti-leishmaniasis vaccine. The classical prokaryote Escherichia coli biosystem failed in accumulating PSA. Consequently, the standard plant system based on N. benthamiana has been optimized for the production of putatively active PSA. First, the RNA silencing defense mechanism set up by the plant against PSA ectopic expression was abolished by using three viral suppressors acting at different steps of the RNA silencing pathway. Then, we demonstrated that the signal peptide at the N-terminal side of the PSA is required for its accumulation. The PSA ER signaling and retention with the PSA signal peptide and the KDEL motif, respectively were optimized to significantly increase its accumulation. Finally, we demonstrate that the production of recombinant PSA in N. benthamiana leaves allows the conservation of its immunogenic property. These approaches demonstrate that based on these optimizations, plant based systems can be used to effectively produce the biological active PSA protein. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

PubMed

Glick, Benjamin S

2014-02-01

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

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.

[Development and medical application of Er-YAG laser].

PubMed

Okamoto, Y; Kobayashi, A; Awazu, A; Ogino, H; Ban, T

1993-09-01

Result of developments of Er-YAG laser and its delivery system were reported. Er-YAG laser's wavelength is 2.94 microns, the beam absorption rate by water is higher than other laser beam. Er-YAG laser has repeated pulse oscillation, pulse width is 400 mu, sec, the repeat frequency is between 5 to 10 pulse per second. The mean power is 4 W maximum, 10 pps. The fibers of laser are made of zirconium-F-glass. We carried out a study on the possible application of the Er-YAG laser on the rabbit arteries and myocardium and human arteries were examined in vitro. Very clear cuts were observed on the histological examination. There were no evidence of thermal damage, no carbonization on the sharp cutting surface. Experimental result showed that Er-YAG lasers had good potential for angioplastic laser.

Comparative efficacy of Er,Cr:YSGG and Er:YAG lasers for etching of composite for orthodontic bracket bonding.

PubMed

Mirhashemi, Amir Hossein; Chiniforush, Nasim; Sharifi, Nastaran; Hosseini, Amir Mehdi

2018-05-01

Several techniques have been proposed to obtain a durable bond, and the efficacy of these techniques is assessed by measuring parameters such as bond strength. Laser has provided a bond strength as high as that of acid etching in vitro and has simpler use with shorter clinical time compared to acid etching. This study aimed to compare the efficacy of Er:YAG and Er,Cr:YSGG lasers for etching and bonding of composite to orthodontic brackets. No previous study has evaluated the effect of these particular types of laser. A total of 70 composite blocks were randomly divided into five groups (n = 14): group 1, etching with phosphoric acid for 20 s; group 2, Er:YAG laser irradiation with 2 W power for 10 s; group 3, Er:YAG laser with 3 W power for 10 s; group 4, Er,Cr:YSGG laser with 2 W power for 10 s; group 5, Er,Cr:YSGG laser with 3 W power for 10 s. Metal brackets were then bonded to composites, and after 5000 thermal cycles, they were subjected to shear bond strength test in a universal testing machine after 24 h of water storage. One sample of each group was evaluated under a scanning electron microscope (SEM) to assess changes in composite surface after etching. The adhesive remnant index (ARI) was calculated under a stereomicroscope. Data were statistically analyzed. The mean and standard deviation of shear bond strength were 18.65 ± 3.36, 19.68 ± 5.34, 21.31 ± 4.03, 17.38 ± 6.94, and 16.45 ± 4.26 MPa in groups 1-5, respectively. The ARI scores showed that the bond failure mode in all groups was mainly mixed. The groups were not significantly different in terms of shear bond strength. Er:YAG and Er,Cr:YSGG lasers with the mentioned parameters yield optimal shear bond strength and can be used as an alternative to acid etching for bracket bond to composite.

Operational durability of a giant ER valve for Braille display

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

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.

Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria

PubMed Central

Briston, Thomas; Lewis, Sian; Koglin, Mumta; Mistry, Kavita; Shen, Yongchun; Hartopp, Naomi; Katsumata, Ryosuke; Fukumoto, Hironori; Duchen, Michael R.; Szabadkai, Gyorgy; Staddon, James M.; Roberts, Malcolm; Powney, Ben

2016-01-01

Growing evidence suggests persistent mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell death underlying a variety of diseases. While it has long been clear the mPTP is a druggable target, current agents are limited by off-target effects and low therapeutic efficacy. Therefore identification and development of novel inhibitors is necessary. To rapidly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve large batches of functionally active mitochondria from cells and tissues. The cryopreserved mitochondria maintained respiratory coupling and ATP synthesis, Ca2+ uptake and transmembrane potential. A high-throughput screen (HTS), using an assay of Ca2+-induced mitochondrial swelling in the cryopreserved mitochondria identified ER-000444793, a potent inhibitor of mPTP opening. Further evaluation using assays of Ca2+-induced membrane depolarisation and Ca2+ retention capacity also indicated that ER-000444793 acted as an inhibitor of the mPTP. ER-000444793 neither affected cyclophilin D (CypD) enzymatic activity, nor displaced of CsA from CypD protein, suggesting a mechanism independent of CypD inhibition. Here we identified a novel, CypD-independent inhibitor of the mPTP. The screening approach and compound described provides a workflow and additional tool to aid the search for novel mPTP modulators and to help understand its molecular nature. PMID:27886240

Upconversion luminescence in Er3+ doped and Er3+/Yb3+ codoped zirconia and hafnia nanocrystals excited at 980 nm

NASA Astrophysics Data System (ADS)

Gómez, Luis A.; Menezes, Leonardo de S.; de Araújo, Cid B.; Gonçalves, Rogeria R.; Ribeiro, Sidney J. L.; Messaddeq, Younes

2010-06-01

Frequency upconversion (UC) luminescence in nanocrystalline zirconia (ZrO2) and hafnia (HfO2) doped with Er3+ and Yb3+ was studied under continuous-wave excitation at 980 nm. Samples of ZrO2:Er3+, ZrO2:Er3+/Yb3+, and HfO2:Er3+/Yb3+ were prepared by the sol-gel technique and characterized using x-ray diffraction and electron microscopy. A study of the infrared-to-green and infrared-to-red UC processes was performed including the analysis of the spectral and the temporal behavior. The mechanisms contributing to the UC luminescence were identified as excited state absorption and energy transfer among rare-earth ions.

Cooperative Dynamics of AR and ER Activity in Breast Cancer

PubMed Central

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

2016-01-01

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

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

Factors That Influence Enrolment and Retention in Ghana' National Health Insurance Scheme.

PubMed

Kotoh, Agnes Millicent; Aryeetey, Genevieve Cecilia; Van der Geest, Sjaak

2017-10-17

The government of Ghana introduced the National Health Insurance Scheme (NHIS) in 2004 with the goal of achieving universal coverage within 5 years. Evidence, however, shows that expanding NHIS coverage and especially retaining members have remained a challenge. A multilevel perspective was employed as a conceptual framework and methodological tool to examine why enrolment and retention in the NHIS remains low. A household survey was conducted after 20 months educational and promotional activities aimed at improving enrolment and retention rates in 15 communities in the Central and Eastern Regions (ERs) of Ghana. Observation, indepth interviews and informal conversations were used to collect qualitative data. Forty key informants (community members, health providers and district health insurance schemes' [DHISs] staff) purposely selected from two casestudy communities in the Central Region (CR) were interviewed. Several community members, health providers and DHISs' staff were also engaged in informal conversations in the other five communities in the region. Also, four staff of the Ministry of Health (MoH), Ghana Health Service (GHS) and National Health Insurance Authority (NHIA) were engaged in in-depth interviews. Descriptive statistics was used to analyse quantitative data. Qualitative data was analysed using thematic content analysis. The results show that factors that influence enrolment and retention in the NHIS are multi-dimensional and cut across all stakeholders. People enrolled and renewed their membership because of NHIS' benefits and health providers' positive behaviour. Barriers to enrolment and retention included: poverty, traditional risk-sharing arrangements influence people to enrol or renew their membership only when they need healthcare, dissatisfaction about health providers' behaviour and service delivery challenges. Given the multi-dimensional nature of barriers to enrolment and retention, we suggest that the NHIA should engage DHISs, health

Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins.

PubMed

Barz, W P; Walter, P

1999-04-01

Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for "delayed GPI-anchored protein transport"), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Delta dgt1Delta cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non-GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Delta dgt1Delta cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Delta dgt1Delta cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins.

Two Endoplasmic Reticulum (ER) Membrane Proteins That Facilitate ER-to-Golgi Transport of Glycosylphosphatidylinositol-anchored Proteins

PubMed Central

Barz, Wolfgang P.; Walter, Peter

1999-01-01

Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for “delayed GPI-anchored protein transport”), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Δ dgt1Δ cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non–GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Δ dgt1Δ cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Δ dgt1Δ cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins. PMID:10198056

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.

Erbium induced magnetic properties of Er/ZnO nanoparticles

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

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

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. %more » of Er while all other samples exhibiting weak ferromagnetic nature.« less

Boulder Valley Kindergarten Study: Retention Practices and Retention Effects.

ERIC Educational Resources Information Center

Shepard, Lorrie A.; Smith, Mary Lee

Having implemented a policy that allowed schools to retain children in kindergarten an extra year, the Boulder Valley Public School District in Colorado conducted a study to determine the cognitive and emotional benefits of retention in kindergarten and the characteristics that led to decisions about retention. The study involved a research review…

SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae

PubMed Central

Lee, Miriam; Ko, Young-Joon; Moon, Yeojin; Han, Minsoo; Kim, Hyung-Wook; Lee, Sung Haeng; Kang, KyeongJin

2015-01-01

Dynamin-like GTPases of the atlastin family are thought to mediate homotypic endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism remains largely unclear. Here, we developed a simple and quantitative in vitro assay using isolated yeast microsomes for measuring yeast atlastin Sey1p-dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE-mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p, another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on isolated microsomes, together with the lack of fusion between Sey1p proteoliposomes even with a 25-fold excess of the physiological concentration of Sey1p, suggests that Sey1p requires additional factors to support ER fusion in vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion is involved in atlastin-initiated homotypic ER fusion. PMID:26216899

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.

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er) § 222.24 Relationship as remarried widow(er). (a) New eligibility. A claimant will have the relationship... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Relationship as remarried widow(er). 222.24...

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

NASA Astrophysics Data System (ADS)

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

1994-05-01

Solid state interdiffusions between a thin film of erbium deposited under vacuum conditions and (001) and (111) GaAs substrates were investigated in the temperature range 350-800 ^{circ}C. Complementary analysis methods (RBS, X-ray diffraction) allow us to point out, according to annealing temperatures, successives steps of the interaction corresponding to different mixtures of phases, essentially binaries. These steps are strongly depending on the GaAs substrate orientation, especially the final step of the interdiffusions. On (001) GaAs, only two steps have been observed : no visible interaction is noticed between erbium and GaAs before 600 ^{circ}C ; the interaction begins at 600 ^{circ}C, evolves slightly and leads at 800 ^{circ}C to the nominal composition " Er{10}GaAs " which corresponds to a mixture of several phases Er5Ga3, Er and ErAs. On (111) GaAs, several steps of interaction have been found ; first of all, erbium reacts with the substrate at 400 ^{circ}C (Er5Ga3 + Er mixture), then the reaction is continuing at 600 ^{circ}C (Er5Ga3 + Er + ErAs mixture) before reaching at 800 ^{circ}C the nominal composition " Er{1,5}GaAs ", which is in fact a mixture of the three binaries ErAs + ErGa2 + Er3Ga5. It can be noticed that the 800 ^{circ}C annealing is not sufficient to reach the mixture of the phases ErAs + Ga which, according to the ternary phase diagram, should be the final stage of the interaction Er/GaAs. The analysis of the Er/GaAs interdiffusions shows that ErAs is the " key " compound around which the interaction progresses. This compound appears as an ideal candidate to realize epitaxial ErAs/GaAs heterostructures. Les interdiffusions en phase solide entre une couche mince d'erbium déposée dans des conditions d'ultra-vide et des substrats de GaAs orientés (001) et (111) ont été étudiées après des traitements thermiques d'une heure entre 350 et 800 ^{circ}C. L'utilisation de techniques complémentaires d'analyse (RBS, diffraction X) a permis

Gingival melanin depigmentation by Er:YAG laser: A literature review.

PubMed

Pavlic, Verica; Brkic, Zlata; Marin, Sasa; Cicmil, Smiljka; Gojkov-Vukelic, Mirjana; Aoki, Akira

2018-04-01

Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO 2 , diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.

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.

Fall 1982 Retention Study.

ERIC Educational Resources Information Center

Peralta Community Coll. District, Oakland, CA. Office of Research, Planning and Development.

In fall 1982, a study was conducted in the Peralta Community College District (PCCD) using withdrawal and grade distribution data to analyze student retention patterns. Successful retention rates were based on the percentage of students who received a passing grade, while total retention rates were based on the percentage of students who received…

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

PubMed

Weaver, D A

Widow benefits have been a part of the Social Security program since the 1939 amendments to the Social Security Act (widower benefits were added later). For many years, the Social Security law called for paying a widow(er) a fraction of the deceased worker's primary insurance amount (PIA). However, the worker--while alive--may have received the full PIA as his or her retirement benefit. Over time, arguments were made that a widow(er) should be treated as generously as his or her spouse was. The 1972 amendments to the Social Security Act allowed for a widow(er) to receive a full PIA, subject to actuarial reductions if the widow(er) benefit was claimed before the normal retirement age (NRA) and subject to a new provision of the law commonly referred to as the widow(er)'s limit. Generally, the widow(er)'s limit specifies that if a worker received reduced retirement benefits (because the worker claimed benefits before the NRA), then the worker's widow(er) cannot receive a monthly benefit equal to the full PIA. Rather, the widow(er)'s benefit is generally limited to the amount the worker would receive if he or she was still alive. The limit provision appears to be motivated by the overall intent of the 1972 Congress to pay a benefit to a widow(er) that was comparable with what the worker received. A number of changes to the limit provision have been discussed. This article looks at the following options: Abolishing the limit, Raising the limit by requiring that it never be set below the average PIA among all retired-worker beneficiaries. Adjusting the limit for some widow(er)s--that is, only persons who are widowed before the NRA (the ARLA option), Making a simpler adjustment to the limit by abolishing it for persons who are widowed before age 62 (the SARLA option), and A proposal by Robert J. Myers that would make modest adjustments to the limit for cases in which the worker died before the NRA. The most fundamental change--abolishing the limit--would increase benefits

Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

PubMed

Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

2015-10-01

The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

The incidence of acute urinary retention secondary to BPH is increasing among California men.

PubMed

Groves, H K; Chang, D; Palazzi, K; Cohen, S; Parsons, J K

2013-09-01

Current epidemiological patterns of adverse events of clinical BPH remain unclear. We investigated trends in acute urinary retention (AUR) associated with BPH in a large, population-based cohort. We utilized the California Office of Statewide Health Planning and Development Database to examine 3 724 016 emergency room (ER) visits in California among men aged  50 years from 2007 to 2010. Outcomes included AUR for which BPH was the primary diagnosis, AUR for which BPH was a secondary diagnosis and urethral catheterization for AUR. We generated adjusted odds ratios (ORadj) using multivariate logistic regression to determine longitudinal trends. A total of 17 023 men presented with a diagnosis of BPH-associated AUR, the unadjusted incidence of which increased from 4.00 per 1000 ER visits in 2007 to 5.23 per 1000 ER visits in 2010 (P<0.001). In adjusted analyses, primary AUR (ORadj=1.25; 95% confidence interval (CI), 1.19-1.32; P<0.001) and secondary AUR (ORadj=1.80; 95% CI, 1.62-2.00; P<0.001) increased 25% and 80%, respectively. Urethral catheterization for primary (ORadj=1.30; 95% CI, 1.22-1.39; P<0.001) and secondary (ORadj=1.82; 95% CI, 1.57-2.11; P<0.001) AUR increased 30% and 82%, respectively. Asian race (P<0.001), Hispanic race (P<0.001) and commercial insurance (P<0.001) were associated with significantly increased risks of AUR and urethral catheterization. Between 2007 and 2010, the observed incidence of BPH-associated AUR increased substantially in a large and ethnically diverse male population of the United States.

Evaluating the potential bioactivity of a novel compound ER1626.

PubMed

Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

2014-01-01

ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis. ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells. In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

PubMed Central

Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jing; Sun, Qian; Guan, Xiaoxiang

2017-01-01

ABSTRACT Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy. PMID:28272969

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.

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

NASA Astrophysics Data System (ADS)

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

2005-12-01

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

Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo.

PubMed

Wires, Emily S; Henderson, Mark J; Yan, Xiaokang; Bäck, Susanne; Trychta, Kathleen A; Lutrey, Molly H; Harvey, Brandon K

2017-01-01

The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. The ability to longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular and cellular adaptations to physiologic or pathologic states, but has been challenging. We recently described the creation of a Gaussia luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc-SERCaMP) to longitudinally monitor ER calcium homeostasis. Here we describe a complementary tool to measure the unfolded protein response (UPR), utilizing a UPRE-driven secreted Nano luciferase (UPRE-secNLuc) to examine the activating transcription factor-6 (ATF6) and inositol-requiring enzyme 1 (IRE1) pathways of the UPR. We observed an upregulation of endogenous ATF6- and XBP1-regulated genes following pharmacologically-induced ER stress that was consistent with responsiveness of the UPRE sensor. Both GLuc and NLuc-based reporters have favorable properties for in vivo studies, however, they are not easily used in combination due to overlapping substrate activities. We describe a method to measure the enzymatic activities of both reporters from a single sample and validated the approach using culture medium and rat blood samples to measure GLuc-SERCaMP and UPRE-secNLuc. Measuring GLuc and NLuc activities from the same sample allows for the robust and quantitative measurement of two cellular events or cell populations from a single biological sample. This study is the first to describe the in vivo measurement of UPRE activation by sampling blood, using an approach that allows concurrent interrogation of two components of ER homeostasis.

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.

Transitions of protein traffic from cardiac ER to junctional SR.

PubMed

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

2015-04-01

The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca(2+) release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQ-DsRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed ((del)TRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and (del)TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic. Copyright © 2015 Elsevier Ltd. All rights reserved.

PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

PubMed Central

Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

2014-01-01

Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

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

ER-plasma membrane junctions: Why and how do we study them?

PubMed

Chang, Chi-Lun; Chen, Yu-Ju; Liou, Jen

2017-09-01

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are membrane microdomains important for communication between the ER and the PM. ER-PM junctions were first reported in muscle cells in 1957, but mostly ignored in non-excitable cells due to their scarcity and lack of functional significance. In 2005, the discovery of stromal interaction molecule 1 (STIM1) mediating a universal Ca 2+ feedback mechanism at ER-PM junctions in mammalian cells led to a resurgence of research interests toward ER-PM junctions. In the past decade, several major advancements have been made in this emerging topic in cell biology, including the generation of tools for labeling ER-PM junctions and the unraveling of mechanisms underlying regulation and functions of ER-PM junctions. This review summarizes early studies, recently developed tools, and current advances in the characterization and understanding of ER-PM junctions. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017 Elsevier B.V. All rights reserved.

Er{sub 1.33}Pt{sub 3}Ga{sub 8}: A modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type

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

Oswald, Iain W.H.; Gourdon, Olivier; Bekins, Amy

Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were synthesized in a molten Ga flux. Er{sub 1.33}Pt{sub 3}Ga{sub 8} can be considered to be a modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type, where the partial occupancies are ordered. Indeed, the presence of weak satellite reflections indicates a complex organization and distribution of the Er and Ga atoms within the [ErGa] slabs. The structure has been solved based on single crystal X-ray diffraction data in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*. Precession images also indicate diffusion in the perpendicular direction indicating a partial disorder ofmore » this arrangement from layer to layer. In addition, Er{sub 1.33}Pt{sub 3}Ga{sub 8} shows antiferromagnetic ordering at T{sub N}~5 K. - Graphical abstract: A precession image of the hk0 zone showing weak, periodic, unindexed reflections indicating modulation and representation of the commensurate [ErGa] layer showing the waving modulated occupation. - Highlights: • Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were grown from gallium flux. • The structure of Er{sub 1.33}Pt{sub 3}Ga{sub 8} is compared to Er{sub 4}Pt{sub 9}Al{sub 24}. • Structure has been solved in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*.« less

Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

PubMed

Assefa, Yibeltal; Worku, Alemayehu; Wouters, Edwin; Koole, Olivier; Haile Mariam, Damen; Van Damme, Wim

2012-01-01

Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

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.

Electroluminescent Yb2O3:Er and Yb2Si2O7:Er nanolaminate films fabricated by atomic layer deposition on silicon

NASA Astrophysics Data System (ADS)

Ouyang, Zhongtao; Yang, Yang; Sun, Jiaming

2018-06-01

Atomic layer doped Yb2O3:Er and Yb2Si2O7:Er nanolaminate films are fabricated on silicon by atomic layer deposition, and ∼1530 nm electroluminescence (EL) is obtained from the metal-oxide-semiconductor light-emitting devices (MOSLEDs) based on these films. The Yb2O3 films transfer to Yb2Si2O7 phase after annealing above 1000 °C. Intense photoluminescence from Yb2Si2O7 film confirms high efficiency and energy transfer under optical excitation, but the limited electron conduction restricts the EL performance. EL from the Yb2O3:Er MOSLED outperforms, presenting an external quantum efficiency up to 8.5% and the power efficiency of 1 × 10-3. The EL is derived to result from the impact excitation of Er3+ ions by hot electrons, which stem from Fowler-Nordheim tunneling mechanism under sufficient bias voltage. The critical distance for the cross relaxation of doped Er3+ ions in nanolaminate Yb2O3 matrix is experimentally determined to be ∼3 nm. Such devices manifest the technological potential of Er-doped Yb-oxides for applications in silicon-based optoelectronics.

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

PubMed

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

2016-03-07

The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lockheed ER-2 high altitude research aircraft

NASA Image and Video Library

1997-11-04

ER-2 tail number 706, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor

PubMed Central

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

2014-01-01

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

“Retention Projection” Enables Reliable Use of Shared Gas Chromatographic Retention Data Across Labs, Instruments, and Methods

PubMed Central

Barnes, Brian B.; Wilson, Michael B.; Carr, Peter W.; Vitha, Mark F.; Broeckling, Corey D.; Heuberger, Adam L.; Prenni, Jessica; Janis, Gregory C.; Corcoran, Henry; Snow, Nicholas H.; Chopra, Shilpi; Dhandapani, Ramkumar; Tawfall, Amanda; Sumner, Lloyd W.; Boswell, Paul G.

2014-01-01

Gas chromatography-mass spectrometry (GC-MS) is a primary tool used to identify compounds in complex samples. Both mass spectra and GC retention times are matched to those of standards, but it is often impractical to have standards on hand for every compound of interest, so we must rely on shared databases of MS data and GC retention information. Unfortunately, retention databases (e.g. linear retention index libraries) are experimentally restrictive, notoriously unreliable, and strongly instrument dependent, relegating GC retention information to a minor, often negligible role in compound identification despite its potential power. A new methodology called “retention projection” has great potential to overcome the limitations of shared chromatographic databases. In this work, we tested the reliability of the methodology in five independent laboratories. We found that even when each lab ran nominally the same method, the methodology was 3-fold more accurate than retention indexing because it properly accounted for unintentional differences between the GC-MS systems. When the labs used different methods of their own choosing, retention projections were 4- to 165-fold more accurate. More importantly, the distribution of error in the retention projections was predictable across different methods and labs, thus enabling automatic calculation of retention time tolerance windows. Tolerance windows at 99% confidence were generally narrower than those widely used even when physical standards are on hand to measure their retention. With its high accuracy and reliability, the new retention projection methodology makes GC retention a reliable, precise tool for compound identification, even when standards are not available to the user. PMID:24205931

The ER in 3D: a multifunctional dynamic membrane network.

PubMed

Friedman, Jonathan R; Voeltz, Gia K

2011-12-01

The endoplasmic reticulum (ER) is a large, singular, membrane-bound organelle that has an elaborate 3D structure with a diversity of structural domains. It contains regions that are flat and cisternal, ones that are highly curved and tubular, and others adapted to form contacts with nearly every other organelle and with the plasma membrane. The 3D structure of the ER is determined by both integral ER membrane proteins and by interactions with the cytoskeleton. In this review, we describe some of the factors that are known to regulate ER structure and discuss how this structural organization and the dynamic nature of the ER membrane network allow it to perform its many different functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Magnetocaloric effect in textured rare earth intermetallic compound ErNi

NASA Astrophysics Data System (ADS)

Sankar, Aparna; Chelvane, J. Arout; Morozkin, A. V.; Nigam, A. K.; Quezado, S.; Malik, S. K.; Nirmala, R.

2018-05-01

Melt-spun ErNi crystallizes in orthorhombic FeB-type structure (Space group Pnma, no. 62) similar to the arc-melted ErNi compound. Room temperature X-ray diffraction (XRD) experiments reveal the presence of texture and preferred crystal orientation in the melt-spun ErNi. The XRD data obtained from the free surface of the melt-spun ErNi show large intensity enhancement for (1 0 2) Bragg reflection. The scanning electron microscopy image of the free surface depicts a granular microstructure with grains of ˜1 μm size. The arc-melted and the melt-spun ErNi compounds order ferromagnetically at 11 K and 10 K (TC) respectively. Field dependent magnetization (M-H) at 2 K shows saturation behaviour and the saturation magnetization value is 7.2 μB/f.u. for the arc-melted ErNi and 7.4 μB/f.u. for the melt-spun ErNi. The isothermal magnetic entropy change (ΔSm) close to TC has been calculated from the M-H data. The maximum isothermal magnetic entropy change, -ΔSmmax, is ˜27 Jkg-1K-1 and ˜24 Jkg-1K-1 for the arc-melted and melt-spun ErNi for 50 kOe field change, near TC. The corresponding relative cooling power values are ˜440 J/kg and ˜432 J/kg respectively. Although a part of ΔSm is lost to crystalline electric field (CEF) effects, the magnetocaloric effect is substantially large at 10 K, thus rendering melt-spun ErNi to be useful in low temperature magnetic refrigeration applications such as helium gas liquefaction.

Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors

PubMed Central

2013-01-01

In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric. PMID:23294730

Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors.

PubMed

Chen, Fa-Hsyang; Her, Jim-Long; Shao, Yu-Hsuan; Matsuda, Yasuhiro H; Pan, Tung-Ming

2013-01-08

In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric.

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

Spectroscopic characterisation of Er-doped LuVO4 single crystals

NASA Astrophysics Data System (ADS)

Lisiecki, R.; Dominiak-Dzik, G.; Solarz, P.; Strzęp, A.; Ryba-Romanowski, W.; Łukasiewicz, T.

2010-12-01

The LuVO4:Er single crystals were grown by the Czochralski technique. The crystal-field split energy levels of Er3+ ion were derived experimentally employing absorption and emission spectra measured at T=10 K. The Judd-Ofelt phenomenological method was used to estimate intensity parameters, radiative lifetimes and branching ratios of luminescence. The excited state dynamics of the LuVO4:Er systems was investigated and experimental lifetimes of emitting levels were measured. The emission cross section of the 4I13/2→4I15/2 transition in the infrared was calculated by the Füchtbauer-Ladenburg method. The gain cross section, estimated for several inverse-population parameters, allowed us to evaluate a potential laser activity of the LuVO4:Er system at 1.6 μm. Also, the potential range of the optical pumping was assessed based on absorption spectra achieved at the room temperature. The optical losses related to the green up-converted emission, encountered under the 978 nm excitation between 300 and 670 K were indicated and discussed. Spectroscopic peculiarities of the Er3+-doped LuVO4 crystal were discussed in relation to optical properties of the YVO4:Er and GdVO4:Er crystals. Taking into account the high quantum efficiency of the 4I13/2 level, and satisfactory absorption and emission features, the LuVO4:Er crystal can be considered as a promising active material for laser operation near 1.6 μm.

Analysis of erythema after Er:YAG laser skin resurfacing.

PubMed

Ko, Na Young; Ahn, Hyo-Hyun; Kim, Soo-Nam; Kye, Young-Chul

2007-11-01

Postoperative erythema can be expected to occur in every patient after laser resurfacing, and pigmentary disturbances may be related to the intensity and the duration of erythema. This study was undertaken to assess the clinical features of erythema, the factors that influence its duration, and the relation between the duration of erythema and the incidence of hyperpigmentation and hypopigmentation in skin of Asian persons after Er:YAG laser resurfacing. A total of 218 patients (skin phototypes III to V) were recruited and treated with a short-pulsed Er:YAG laser, a variable-pulsed Er:YAG laser, or a dual-mode Er:YAG laser for skin resurfacing. Clinical assessments were performed retrospectively using medical charts and serial photographs. Postoperative erythema was observed in all patients after Er:YAG laser resurfacing with a mean duration of 4.72 months. In 98.2% of patients, erythema faded completely within 12 months. Postinflammatory hyperpigmentation was observed in 38.1% of patients after Er:YAG laser resurfacing. Skin phototype, level of ablation, and depth of thermal damage caused by a long-pulsed laser appear to be important factors that affect the duration of erythema. Moreover, prolonged erythema was related to the risk of postinflammatory hyperpigmentation.

Initiation and execution of lipotoxic ER stress in pancreatic β-cells

PubMed Central

Cunha, Daniel A.; Hekerman, Paul; Ladrière, Laurence; Bazarra-Castro, Angie; Ortis, Fernanda; Wakeham, Marion C.; Moore, Fabrice; Rasschaert, Joanne; Cardozo, Alessandra K.; Bellomo, Elisa; Overbergh, Lutgart; Mathieu, Chantal; Lupi, Roberto; Hai, Tsonwin; Herchuelz, Andre; Marchetti, Piero; Rutter, Guy A.; Eizirik, Décio L.; Cnop, Miriam

2013-01-01

Summary Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP. PMID:18559892

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

[Up-conversion luminescent materials of Y2O3: RE(RE=Er or Er/Yb) prepared by sol-gel combustion synthesis].

PubMed

Han, Peng-de; Zhang, Le; Huang, Xiao-gu; Wang, Li-xi; Zhang, Qi-tu

2010-11-01

Y2O3 powders doped with rare-earth ions were synthesized by sol-gel combustion synthesis. Effects of different calcinating temperatures, Er+ doping concentration and Yb3+ doping concentration were investigated. It was shown that the single well crystallized Y2O3 powders could be obtained at 800 degrees C; as the calcinating temperature increased, the crystallinity and upconversion luminescence intensity were higher; the particle size was uniform around 1 microm at 900 degrees C; when Er3+ doping concentration was 1 mol%, the green upconversion luminescence intensity reached the maximum, but for red upconversion luminescence, when Er3+ doping concentration was 4 mol%, its luminescence intensity reached the maximum; as the ratio of Yb3+ to Er3+ was 4:1, the green emission intensity reached the maximum, while the red emission intensity was always increasing as Yb3+ doping concentration increased.

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

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

PubMed

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

2014-09-01

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

Temperature Effects of Dielectric Properties of ER Fluids

NASA Astrophysics Data System (ADS)

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

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

On the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 4+} co-diffusion

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

Almeida, José Manuel Marques Martins de, E-mail: jmmma@utad.pt; Department of Physics, School of Science and Technology, University of Trás-os-Montes e Alto Douro, PO. Box 1013, 5001-801 Vila Real; Sada, Cinzia

2016-02-15

Highlights: • Enhancement of the diffusion of erbium ions (Er{sup 3+}) in lithium niobate crystals. • Incoherence on published results lead to need for systematic revision of literature. • Further insight into the topic of co-diffusion of Er{sup 3+}/Ti{sup 4+} ions into LiNbO{sub 3}. - Abstract: After carrying out a revision of the literature on the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 4+} co-diffusion and analyzing our own experimental results, we conclude that no reproducible results were reported, meaning that further research on this subject is necessary.

Aging induced ER stress alters sleep and sleep homeostasis

PubMed Central

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2014-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

Getting ER into the Curriculum: No More Excuses!

ERIC Educational Resources Information Center

Ewert, Doreen

2017-01-01

Extensive reading (ER) is a research and theory-supported approach for language and reading development in an additional language, yet its implementation is limited, particularly in English-dominant contexts. This article addresses many of the uncertainties and perceived obstacles to adding ER to a language curriculum. After reviewing relevant…

Clad-pumped Er-nanoparticle-doped fiber laser (Conference Presentation)

NASA Astrophysics Data System (ADS)

Baker, Colin C.; Friebele, E. Joseph; Rhonehouse, Daniel L.; Marcheschi, Barbara A.; Peele, John R.; Kim, Woohong; Sanghera, Jasbinder S.; Zhang, Jun; Chen, Youming; Pattnaik, Radha K.; Dubinskii, Mark

2017-03-01

Erbium-doped fiber lasers are attractive for directed energy weapons applications because they operate in a wavelength region that is both eye-safer and a window of high atmospheric transmission. For these applications a clad-pumped design is desirable, but the Er absorption must be high because of the areal dilution of the doped core vs. the pump cladding. High Er concentrations typically lead to Er ion clustering, resulting in quenching and upconversion. Nanoparticle (NP) doping of the core overcomes these problems by physically surrounding the Er ions with a cage of Al and O in the NP, which keeps them separated to minimize excited state energy transfer. A significant issue is obtaining high Er concentrations without the NP agglomeration that degrades the optical properties of the fiber core. We have developed the process for synthesizing stable Er-NP suspension which have been used to fabricate EDFs with Er concentrations >90 dB/m at 1532 nm. Matched clad fibers have been evaluated in a core-pumped MOPA with pump and signal wavelengths of 1475 and 1560 nm, respectively, and efficiencies of 72% with respect to absorbed pump have been obtained. We have fabricated both NP- and solution-doped double clad fibers, which have been measured in a clad-pumped laser testbed using a 1532 nm pump. The 1595 nm laser efficiency of the NP-doped fiber was 47.7%, which is high enough for what is believed to be the first laser experiment with the cladding pumped, NP-doped fiber. Further improvements are likely with a shaped cladding and new low-index polymer coatings with lower absorption in the 1500 - 1600 nm range.

Urinary Retention Associated with Stroke.

PubMed

Umemura, Takeru; Ohta, Hirotsugu; Yokota, Akira; Yarimizu, Shiroh; Nishizawa, Shigeru

Patients often exhibit urinary retention following a stroke. Various neuropathological and animal studies have implicated the medulla oblongata, pons, limbic system, frontal lobe as areas responsible for micturition control, although the exact area responsible for urinary retention after stroke is not clear. The purpose of this study was to identify the stroke area responsible for urinary retention by localizing the areas where strokes occur. We assessed 110 patients with cerebral infarction and 27 patients with cerebral hemorrhage (78 men, 59 women; mean age, 73.0 years) who had been admitted to our hospital between October, 2012 and September, 2013. We used computed tomography (CT) and magnetic resonance imaging (MRI) to investigate the stroke location, and evaluated whether post-stroke urinary retention occurred. Twelve (8.8%) of the 137 patients (7 men, 5 women; mean age, 78.8 years) exhibited urinary retention after a stroke. Stroke occurred in the right/left dominant hemisphere in 7 patients; nondominant hemisphere in 1; cerebellum in 3; and brainstem in 1. Strokes in the dominant hemisphere were associated with urinary retention (P = 0.0314), particularly in the area of the insula (P < 0.01). We concluded that stroke affecting the insula of the dominant hemisphere tends to cause urinary retention.

Mobile Learning and Student Retention

ERIC Educational Resources Information Center

Fozdar, Bharat Inder; Kumar, Lalita S.

2007-01-01

Student retention in open and distance learning (ODL) is comparatively poor to traditional education and, in some contexts, embarrassingly low. Literature on the subject of student retention in ODL indicates that even when interventions are designed and undertaken to improve student retention, they tend to fall short. Moreover, this area has not…

Beta-glucosidase activity of ER-bodies in Arabidopsis thaliana seedlings under clinorotation and after X-ray irradiation

NASA Astrophysics Data System (ADS)

Romanchuk, Svitlana

Realization of long-term space flight requires the life support bioregenerative systems, an indispensable component of which are plants as a source of oxygen, water and food. Although it is well known now that plants adopt to spaceflight factors, in particular to microgravity, by changing some their patterns at the cellular, physiological, biochemical and molecular levels, many questions on cause and effect of these changes are still open. In addition, it is necessary to find the plant species which will be the most suited to the conditions in a space craft cabin. Plants of the family Brassicaceae are known to be resistant to a variety of abiotic stresses, including irradiation. Among them there are many cultivated plants with which we encounter every day: cabbage, radish, mustard, rapeseed, etc., and Arabidopsis thaliana - a convenient model object. The family Brassicaceae to be characterized by the presence of ER-bodies in plant cells, which are derivative of granular endoplasmic reticulum. Earlier, an enzyme beta-glucosidase (beta-D-glucoside glucohydrolase; EC 3.2.1.21) with an ER retention signal has been shown to accumulate selectively in such bodies in response to different unfavorable factors. Recently, we reported that formation of ER-bodies in A. thaliana seedling roots is sensitive to the clinorotation and X-ray irradiation, as their quantity and size in creased under the influence of these factors in comparison with control.begin{itemize} Therefore, we determined the beta-glucosidase activity in A. thaliana (line Columbia) seedlings grown in the stationary conditions and under clinorotation (a); and after X-ray irradiation (b): a) 3- and 7-day-old seedlings grown on a slow horizontal clinostat (2rpm); b) 3-day-old seedlings were treated with X-ray radiation dose of 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10 and 12 Gray. For the first time, an increase in beta-glucosidase activity, which is the main component of the ER-bodies in A. thaliana seedlings, were found

Harvard ER-2 OH laser-induced fluorescence instrument

NASA Technical Reports Server (NTRS)

Wennberg, Paul O.; Anderson, James G.

1994-01-01

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

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

5 CFR 536.301 - Mandatory pay retention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Mandatory pay retention. 536.301 Section... PAY RETENTION Pay Retention § 536.301 Mandatory pay retention. (a) Subject to the requirements in § 536.102 and this section, an agency must provide pay retention to an employee who moves between...

Electrorheological (ER) Fluids: A Research Needs Assessment

DTIC Science & Technology

1993-05-01

transmission, and to reduce energy loss and damage due to vibration and oscillation. A large number and variety of ER devices have been invented; they are...suspension must be stabilized to prevent settling. Separation could cause loss of fluid performance, plugging of flow paths, and other problems...performa.ice of ER fluids, especially those containing water, can change with time as a result of component loss through evaporation at elevated use

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

PubMed

Costello, Joseph L; Castro, Inês G; Hacker, Christian; Schrader, Tina A; Metz, Jeremy; Zeuschner, Dagmar; Azadi, Afsoon S; Godinho, Luis F; Costina, Victor; Findeisen, Peter; Manner, Andreas; Islinger, Markus; Schrader, Michael

2017-02-01

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A-binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering. © 2017 Costello et al.

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

PubMed Central

Costello, Joseph L.; Hacker, Christian; Schrader, Tina A.; Zeuschner, Dagmar; Findeisen, Peter

2017-01-01

Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering. PMID:28108524

Interleukin 17A exacerbates ER-stress-mediated inflammation of macrophages following ICH.

PubMed

Yang, Zhao; Liu, Qingjun; Shi, Hui; Jiang, Xuheng; Wang, Song; Lu, Yuanlan; Zhang, Ji; Huang, Xiaofei; Yu, Anyong

2018-05-30

IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measured in vitro. In addition, brain edema and brain injury in ICH mice were assessed in vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammation in vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice. In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH. Copyright © 2018. Published by Elsevier Ltd.

Teacher Retention: Problems and Solutions

ERIC Educational Resources Information Center

McLaurin, Sidney E.; Smith, Willis; Smillie, Amanda

2009-01-01

There is a teacher retention crisis in the United States. The purpose of this paper is to answer the following questions: What contributes to teachers leaving the field? How has "No Child Left Behind" affected teacher retention? What can be done to retain good teachers? What impact do school administrators have on teacher retention?…

Enhancement of Er optical efficiency through bismuth sensitization in yttrium oxide

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

Scarangella, Adriana; Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania; Reitano, Riccardo

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 themore » 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.« less

Does skill retention benefit from retentivity and symbolic rehearsal? - two studies with a simulated process control task.

PubMed

Kluge, Annette; Frank, Barbara; Maafi, Sanaz; Kuzmanovska, Aleksandra

2016-05-01

Two experiments were designed to compare two symbolic rehearsal refresher interventions (imaginary practice, a hidden introspective process) and investigate the role of retentivity in skill retention. Retentivity is investigated as the ability to memorise and reproduce information and associations that were learned a short time ago. Both experiments comprised initial training (week 1), a symbolic rehearsal for the experimental group (week 2) and a retention assessment (week 3). In the first study, the experimental group received a symbolic rehearsal, while the control group received no rehearsal. In the second study, the experimental group received the same symbolic rehearsal used in study 1, enhanced with rehearsal tasks addressing human-computer interaction. The results showed that both symbolic rehearsal interventions were equally likely to mitigate skill decay. The retentivity showed medium to high correlations with skill retention in both studies, and the results suggest that subjects high in retentivity benefit more from a symbolic rehearsal refresher intervention. Practitioner Summary: Skill decay becomes a problem in situations in which jobs require the correct mastery of non-routine situations. Two experimental studies with simulated process control tasks showed that symbolic rehearsal and retentivity can significantly mitigate skill decay and that subjects higher in retentivity benefit more from refresher interventions.

Visible upconversion emission and non-radiative direct Yb 3+ to Er 3+ energy transfer processes in nanocrystalline ZrO 2:Yb 3+,Er 3+

NASA Astrophysics Data System (ADS)

Diaz-Torres, L. A.; Meza, O.; Solis, D.; Salas, P.; De la Rosa, E.

2011-06-01

Wide band gap Yb 3+ and Er 3+ codoped ZrO 2 nanocrystals have been synthesized by a modified sol-gel method. Under 967 nm excitation strong green and red upconversion emission is observed for several Er 3+ to Yb 3+ ions concentration ratios. A simple microscopic rate equation model is used to study the effects of non-radiative direct Yb 3+ to Er 3+ energy transfer processes on the visible and near infrared fluorescence decay trends of both Er 3+ and Yb 3+ ions. The microscopic rate equation model takes into account the crystalline phase as well as the size of nanocrystals. Nanocrystals phase and size were estimated from XRD patterns. The rate equation model succeeds to fit simultaneously all visible and near infrared fluorescence decay profiles. The dipole-dipole interaction parameters that drive the non-radiative energy transfer processes depend on doping concentration due to crystallite phase changes. In addition the non-radiative relaxation rate ( 4I11/2→ 4I13/2) is found to be greater than that estimated by the Judd-Ofelt parameters due to the action of surface impurities. Results suggest that non-radiative direct Yb 3+ to Er 3+ energy transfer processes in ZrO 2:Yb,Er are extremely efficient.

ER Consolidated Qtrly Rpt_April thru June 2015_October 2015

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

Cochran, John

2015-10-01

This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit, and the Compliance Order on Consent. The 13 sites in the Corrective Action process are listed in Table I-1. Because the status of any Long-Term Stewardship (LTS) activity is detailed in other reports, Section I.3.0 (titled Long-Term Stewardship Work Completed) will not be presented in future ER Quarterly Reports. Section I.3.0 of this ER Quarterly Report identifies the other reports that detail LTS activities.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

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

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2016-05-06

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.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

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

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.

Nursing Student Retention in Associate Degree Nursing Programs Utilizing a Retention Specialist

ERIC Educational Resources Information Center

Schrum, Ronna A.

2014-01-01

The purpose of this study was to examine specific variables associated with nursing student retention in Associate Degree Nursing (ADN) Programs. Jeffreys (2004) Nursing Undergraduate Retention and Success (NURS) conceptual model provided the framework for this descriptive correlational study. One hundred sixty eight pre-licensure associate degree…

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

PubMed

Ivanciuc, O; Ivanciuc, T; Klein, D J; Seitz, W A; Balaban, A T

2001-02-01

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

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.

Evaluation of the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals.

PubMed

Cheng, Xiaogang; Guan, Sumin; Lu, Hong; Zhao, Chunmiao; Chen, Xingxing; Li, Na; Bai, Qian; Tian, Yu; Yu, Qing

2012-12-01

In recent years, various laser systems have been introduced into the field of laser-assisted endodontic therapy. The aim of this study was to evaluate the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals compared with standard endodontic treatment of 5.25% sodium hypochlorite (NaClO) irrigation. Two hundred and twenty infected root canals from extracted human teeth (contaminated with Enterococcus faecalis ATCC 4083 for 4 weeks) were randomly divided into five experimental groups (Nd:YAG, Er:YAG + 5.25% NaClO + 0.9% normal saline + distilled water (Er:YAG/NaClO/NS/DW), Er:YAG + 0.9% normal saline + distilled water (Er:YAG/NS/DW), Er,Cr:YSGG, and aPDT) and two control groups (5.25% NaClO as positive control and 0.9% normal saline (NS) as negative control). The numbers of bacteria on the surface of root canal walls and at different depths inside dentinal tubules before and after treatment were analyzed by means of one-way analysis of variance (one-way ANOVA). The morphology of bacterial cells before and after treatment was examined by scanning electron microscopy (SEM). After treatment, the bacterial reductions in the experimental groups and the positive control group were significantly greater than that of the negative control group (P < 0.001). However, only Er:YAG/NaClO/NS/DW group showed no bacterial growth (the bacterial reduction reached up to 100%) on the surface of root canal walls or at 100/200 µm inside the dentinal tubules. All the laser radiation protocols tested, especially Er:YAG/NaClO/NS/DW, have effective bactericidal effect in experimentally infected root canals. Er:YAG/NaClO/NS/DW seems to be an ideal protocol for root canal disinfection during endodontic therapy. Copyright © 2012 Wiley Periodicals, Inc.

An ab initio-based Er–He interatomic potential in hcp Er

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

Yang, Li; ye, Yeting; Fan, K. M.

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.more » 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.« less

Job embeddedness and nurse retention.

PubMed

Reitz, O Ed; Anderson, Mary Ann; Hill, Pamela D

2010-01-01

Nurse retention is a different way of conceptualizing the employer-employee relationship when compared with turnover. Job embeddedness (JE), a construct based on retention, represents the sum of reasons why employees remain at their jobs. However, JE has not been investigated in relation to locale (urban or rural) or exclusively with a sample of registered nurses (RNs). The purpose of this study was to determine what factors (JE, age, gender, locale, and income) help predict nurse retention. A cross-sectional mailed survey design was used with RNs in different locales (urban or rural). Job embeddedness was measured by the score on the composite, standardized instrument. Nurse retention was measured by self-report items concerning intent to stay. A response rate of 49.3% was obtained. The typical respondent was female (96.1%), white, non-Hispanic (87.4%), and married (74.9%). Age and JE were predictive of nurse retention and accounted for 26% of the explained variance in intent to stay. Although age was a significant predictor of intent to stay, it accounted for only 1.4% of the variance while JE accounted for 24.6% of the variance of nurse retention (as measured by intent to stay). Older, more "embedded" nurses are more likely to remain employed in their current organization. Based on these findings, JE may form the basis for the development of an effective nurse retention program.

Structural Analysis of the QCM Aboard the ER-2

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

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

PubMed Central

Renvoisé, Benoît; Blackstone, Craig

2010-01-01

The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network of smooth tubules extending throughout the cell. Though protein biosynthesis, transport, and quality control in the ER have been extensively studied, mechanisms underlying the heterogeneous architecture of the ER have been clarified more recently. These insights have increased interest in ER morphology changes associated with the development of neuronal axons and dendrites as well as their integration with pre- and postsynaptic signaling pathways. A number of proteins involved in shaping and distributing the ER network are mutated in neurological disorders, particularly the hereditary spastic paraplegias, emphasizing the importance of proper ER morphology for the establishment and maintenance of highly-polarized neurons. PMID:20678923

Gene therapy to target ER stress in brain diseases.

PubMed

Valenzuela, Vicente; Martínez, Gabriela; Duran-Aniotz, Claudia; Hetz, Claudio

2016-10-01

Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrical properties of Er-doped CdS thin films

NASA Astrophysics Data System (ADS)

Dávila-Pintle, J. A.; Lozada-Morales, R.; Palomino-Merino, M. R.; Rivera-Márquez, J. A.; Portillo-Moreno, O.; Zelaya-Angel, O.

2007-01-01

Cadmium sulfide thin films were prepared by chemical bath on glass substrates at 80°C. CdS was Er-doped during the growth process by adding water-diluted Er(NO3)33•H2O to the CdS aqueous growing solution. The relative volume of the doping solution was varied in order to obtain different doping levels. The crystalline structure of CdS:Er films was cubic zinc blende for all the doped layers prepared. The (111) interplanar distance has an irregular variation with the Er doping level. Consequently, the band gap energy (Eg) firstly increases and afterward diminishes becoming, at last, approximately constant at around Eg=2.37eV. For higher doping levels, in the as-grown films, dark electrical conductivity (σ ) values reach 1.8×10-2Ω-1cm-1 at room temperature. The logarithm of σ vs 1/kT plot, where k is Boltzmann's constant and T the absolute temperature, indicates an effective doping of CdS as a result of the Er introduction into the lattice of the material. Hall effect measurements reveal a n-type doping with 2.8×1019cm-3 as maximum carrier density.

Calculation of Retention Time Tolerance Windows with Absolute Confidence from Shared Liquid Chromatographic Retention Data

PubMed Central

Boswell, Paul G.; Abate-Pella, Daniel; Hewitt, Joshua T.

2015-01-01

Compound identification by liquid chromatography-mass spectrometry (LC-MS) is a tedious process, mainly because authentic standards must be run on a user’s system to be able to confidently reject a potential identity from its retention time and mass spectral properties. Instead, it would be preferable to use shared retention time/index data to narrow down the identity, but shared data cannot be used to reject candidates with an absolute level of confidence because the data are strongly affected by differences between HPLC systems and experimental conditions. However, a technique called “retention projection” was recently shown to account for many of the differences. In this manuscript, we discuss an approach to calculate appropriate retention time tolerance windows for projected retention times, potentially making it possible to exclude candidates with an absolute level of confidence, without needing to have authentic standards of each candidate on hand. In a range of multi-segment gradients and flow rates run among seven different labs, the new approach calculated tolerance windows that were significantly more appropriate for each retention projection than global tolerance windows calculated for retention projections or linear retention indices. Though there were still some small differences between the labs that evidently were not taken into account, the calculated tolerance windows only needed to be relaxed by 50% to make them appropriate for all labs. Even then, 42% of the tolerance windows calculated in this study without standards were narrower than those required by WADA for positive identification, where standards must be run contemporaneously. PMID:26292624

Calculation of retention time tolerance windows with absolute confidence from shared liquid chromatographic retention data.

PubMed

Boswell, Paul G; Abate-Pella, Daniel; Hewitt, Joshua T

2015-09-18

Compound identification by liquid chromatography-mass spectrometry (LC-MS) is a tedious process, mainly because authentic standards must be run on a user's system to be able to confidently reject a potential identity from its retention time and mass spectral properties. Instead, it would be preferable to use shared retention time/index data to narrow down the identity, but shared data cannot be used to reject candidates with an absolute level of confidence because the data are strongly affected by differences between HPLC systems and experimental conditions. However, a technique called "retention projection" was recently shown to account for many of the differences. In this manuscript, we discuss an approach to calculate appropriate retention time tolerance windows for projected retention times, potentially making it possible to exclude candidates with an absolute level of confidence, without needing to have authentic standards of each candidate on hand. In a range of multi-segment gradients and flow rates run among seven different labs, the new approach calculated tolerance windows that were significantly more appropriate for each retention projection than global tolerance windows calculated for retention projections or linear retention indices. Though there were still some small differences between the labs that evidently were not taken into account, the calculated tolerance windows only needed to be relaxed by 50% to make them appropriate for all labs. Even then, 42% of the tolerance windows calculated in this study without standards were narrower than those required by WADA for positive identification, where standards must be run contemporaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural products targeting ER stress pathway for the treatment of cardiovascular diseases.

PubMed

Choy, Ker Woon; Murugan, Dharmani; Mustafa, Mohd Rais

2018-04-21

Endoplasmic reticulum (ER) is the main organelle for the synthesis, folding, and processing of secretory and transmembrane proteins. Pathological stimuli including hypoxia, ischaemia, inflammation and oxidative stress interrupt the homeostatic function of ER, leading to accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers a complex signalling network referred as the unfolded protein response (UPR). Extensive studies have demonstrated that ER stress plays an important role in the pathogenesis of various cardiovascular diseases such as heart failure, ischemic heart disease and atherosclerosis. The importance of natural products in modern medicine are well recognized and continues to be of interests as a source of novel lead compounds. Natural products targeting components of UPR and reducing ER stress offers an innovative strategic approach to treat cardiovascular diseases. In this review, we discussed several therapeutic interventions using natural products with potential cardiovascular protective properties targeting ER stress signalling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

ER Consolidated Qtrly Rpt_April-June 2016_October 2016

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

Cochran, John R.

2016-10-01

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 April, May, and June 2016 quarterly reporting period.

Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

PubMed

Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

2015-07-21

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Hereditary Spastic Paraplegia-Linked REEP1 Modulates ER-Mitochondria Contacts

PubMed Central

Lim, Youngshin; Cho, Il-Taeg; Schoel, Leah J.; Cho, Ginam; Golden, Jeffrey A.

2015-01-01

Objective Mutations in receptor expression enhancing protein 1 (REEP1) are associated with hereditary spastic paraplegias (HSPs). Although axonal degeneration is thought to be a predominant feature in HSP, the role of REEP1 mutations in degeneration is largely unknown. Previous studies have implicated a role for REEP1 in the ER, whereas others localized REEP1 with mitochondria. We sought to resolve the cellular localization of REEP1 and to further elucidate the pathobiology underlying REEP1 mutations in patients. Methods A combination of cellular imaging and biochemical approaches was used to refine the cellular localization of REEP1. Next, Reep1 mutations associated with HSP were functionally tested in neuritic growth and degeneration assays using mouse cortical culture. Finally, a novel assay was developed and used with wild type and mutant Reep1s to measure the interactions between the ER and mitochondria. Results We found that REEP1 is present at the ER-mitochondria interface, and it contains subdomains for mitochondrial as well as ER localization. Knockdown of Reep1 and the expression of pathological Reep1 mutations resulted in neuritic growth defects and degeneration. Finally, using our novel split-RLuc8 assay, we show REEP1 facilitates ER-mitochondria interactions, a function diminished by disease-associated mutations. Interpretation Our data potentially reconcile the current conflicting reports regarding REEP1 being either an ER or a mitochondrial protein. Furthermore, our results connect, for the first time, the disrupted ER-mitochondria interactions to a failure in maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a new tool to identify potential drugs for multiple neurodegenerative diseases with ER-mitochondria interaction defects. PMID:26201691

Inhibition of Human MCF-7 Breast Cancer Cells and HT-29 Colon Cancer Cells by Rice-Produced Recombinant Human Insulin-Like Growth Binding Protein-3 (rhIGFBP-3)

PubMed Central

Liu, Lizhong; Liu, Qiaoquan; Lan, Linlin; Tong, Peter C. Y.; Sun, Samuel S. M.

2013-01-01

Background Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. Methodology/Principal Findings We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ±3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice. Conclusion/Significance These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future. PMID:24143239

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.

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

PubMed Central

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

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

ER/Golgi trafficking is facilitated by unbranched actin filaments containing Tpm4.2.

PubMed

Kee, Anthony J; Bryce, Nicole S; Yang, Lingyan; Polishchuk, Elena; Schevzov, Galina; Weigert, Roberto; Polishchuk, Roman; Gunning, Peter W; Hardeman, Edna C

2017-10-01

We have identified novel actin filaments defined by tropomyosin Tpm4.2 at the ER. EM analysis of mouse embryo fibroblasts (MEFs) isolated from mice expressing a mutant Tpm4.2 (Tpm4 Plt53/Plt53 ), incapable of incorporating into actin filaments, revealed swollen ER structures compared with wild-type (WT) MEFs (Tpm4 +/+ ). ER-to-Golgi, but not Golgi-to-ER trafficking was altered in the Tpm4 Plt53/Plt53 MEFs following the transfection of the temperature sensitive ER-associated ts045-VSVg construct. Exogenous Tpm4.2 was able to rescue the ER-to-Golgi trafficking defect in the Tpm4 Plt53/Plt53 cells. The treatment of WT MEFs with the myosin II inhibitor, blebbistatin, blocked the Tpm4.2-dependent ER-to-Golgi trafficking. The lack of an effect on ER-to-Golgi trafficking following treatment of MEFs with CK666 indicates that branched Arp2/3-containing actin filaments are not involved in anterograde vesicle trafficking. We propose that unbranched, Tpm4.2-containing filaments have an important role in maintaining ER/Golgi structure and that these structures, in conjunction with myosin II motors, mediate ER-to-Golgi trafficking. © 2017 Wiley Periodicals, Inc.

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

NASA Image and Video Library

1998-11-17

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.

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

NASA Image and Video Library

2001-08-01

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.

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

NASA Image and Video Library

1998-12-18

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.

ASCORBIC ACID RETENTION AND COLOR OF STRAWBERRIES AS RELATED TO LOW-LEVEL IRRADIATION AND STORAGE TIME

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

Wells, C.E.; Tichenor, D.A.; Martin, D.C.

1963-01-01

Freshly picked strawberries were irradiated in a gamma source and ascorbic acid (ASA) and its oxidative breakdown products were measured at intervals during 3 to 6 months' storage. Reduced ASA, dehydroascorbic acid (DHA), diketogulonic acid (DKA), and total ASA were determined in unirradiated strawberries and in strawberries receiving 0.3 and 0.8 Mrad. Irradiation caused a significant loss of total ASA. Storage at 35 un. Concent 85% F for 180 days resulted in further losses, most of which occurred during the first 95 days. Addition of a glucose oxidase packet to atmospheric packs did not affect retention of total ASA. Amore » significant amount of reduced ASA was destroyed by irradiation, the loss being greater at the higher level used. Relatively large amounts er irradiation in the presence of almost complete retention of total ASA indicated that the degradation followed the usual pattern: reduced ASA to DHA to DKA. After 180 days storage, practically all of the reduced ASA was destroyed in air-packed irradiated samples, but comparable glucose-oxidase-packed samples retained 33 to 47% of their original reduced ASA. Measurement of the Gardner a color value revealed a significant able color variability among samples. Color losses were higher at higher doses. (H.R.D.)« less

Antecedent Wetness Conditions based on ERS scatterometer data in support to rainfall-runoff modeling

NASA Astrophysics Data System (ADS)

Brocca, L.; Melone, F.; Moramarco, T.

2009-04-01

Despite of its small volume compared to other components of the hydrologic cycle, the soil moisture is of fundamental importance to many hydrological, meteorological, biological and biogeochemical processes. For storm rainfall-runoff modeling the estimation of the Antecedent Wetness Conditions (AWC) is one of the most important issues to determine the hydrological response. In this context, this study investigates the potential of the scatterometer on board of the ERS satellites for the assessment of soil wetness conditions at two different scales. The satellite soil moisture data set, available from 1992, is downloaded from the ERS/METOP Soil Moisture archive located at http://www.ipf.tuwien.ac.at/radar/index.php?go=ascat. At the local scale, the scatterometer-derived soil wetness index (SWI) data (Wagner, W., Lemoine, G., and Rott, H., 1999. A Method for Estimating Soil Moisture from ERS Scatterometer and Soil Data. Remote Sensing of Environment, 70, 191-207) have been compared with two in-situ soil moisture data sets. At the catchment scale, the reliability of the SWI to estimate the AWC has been tested considering its relationship with the soil potential maximum retention parameter, S, of the Soil Conservation Service-Curve Number (SCS-CN) method for abstraction. The parameter S has been derived by considering several flood events occurred from 1992 to 2005 in different catchments of central Italy. The performance of two Antecedent Precipitation Indices (API) and one Base Flow Index (BFI), usually employed in the hydrological practice for the AWC assessment, have been compared with the SWI. The obtained results show a high accuracy of the SWI for the estimation of wetness conditions both at the local and catchment scale despite of the complex orography of the investigated areas (Brocca, L., Melone, F., Moramarco, T., Morbidelli, R., 2009. Antecedent wetness conditions based on ERS scatterometer data. Journal of Hydrology, 364 (1-2), 73-87). At the local scale

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

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

PubMed

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

2015-01-01

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

Interfacial structure of two-dimensional epitaxial Er silicide on Si(111)

NASA Astrophysics Data System (ADS)

Tuilier, M. H.; Wetzel, P.; Pirri, C.; Bolmont, D.; Gewinner, G.

1994-07-01

Auger-electron diffraction (AED) and surface-extended x-ray-absorption fine structure (SEXAFS) have been used to obtain a complete description of the atomic structure of a two-dimensional epitaxial Er silicide layer on Si(111). AED reveals that a monolayer of Er is located underneath a buckled Si double layer. The relevant Er-Si interlayer spacings are determined by means of single scattering cluster simulations and a R-factor analysis to be 1.92+/-0.05 Å to the first and 2.70+/-0.05 Å to the second Si top layer. Er near-neighbor bond lengths and coordination numbers are obtained independently from polarization-dependent SEXAFS. The SEXAFS data, when combined with the Si top-layer geometry inferred from AED, permit the determination of the atomic positions at the silicide/Si(111) interface. The Er is found to reside in relaxed T4 sites of Si(111) with a single Er-Si distance of 3.09+/-0.04 Å to the first- and second-layer Si atoms of the substrate.

IRE1: ER stress sensor and cell fate executor

PubMed Central

Chen, Yani; Brandizzi, Federica

2013-01-01

Cells operate a signaling network termed unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). IRE1 is an ER transmembrane sensor that activates UPR to maintain ER and cellular function. While mammalian IRE1 promotes cell survive, it can initiate apoptosis via decay of anti-apoptotic microRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. PMID:23880584

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

PubMed

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

2008-11-01

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

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

Golgi-to-Endoplasmic Reticulum (ER) Retrograde Traffic in Yeast Requires Dsl1p, a Component of the ER Target Site that Interacts with a COPI Coat Subunit

PubMed Central

Reilly, Barbara A.; Kraynack, Bryan A.; VanRheenen, Susan M.; Waters, M. Gerard

2001-01-01

DSL1 was identified through its genetic interaction with SLY1, which encodes a t-SNARE-interacting protein that functions in endoplasmic reticulum (ER)-to-Golgi traffic. Conditional dsl1 mutants exhibit a block in ER-to-Golgi traffic at the restrictive temperature. Here, we show that dsl1 mutants are defective for retrograde Golgi-to-ER traffic, even under conditions where no anterograde transport block is evident. These results suggest that the primary function of Dsl1p may be in retrograde traffic, and that retrograde defects can lead to secondary defects in anterograde traffic. Dsl1p is an ER-localized peripheral membrane protein that can be extracted from the membrane in a multiprotein complex. Immunoisolation of the complex yielded Dsl1p and proteins of ∼80 and ∼55 kDa. The ∼80-kDa protein has been identified as Tip20p, a protein that others have shown to exist in a tight complex with Sec20p, which is ∼50 kDa. Both Sec20p and Tip20p function in retrograde Golgi-to-ER traffic, are ER-localized, and bind to the ER t-SNARE Ufe1p. These findings suggest that an ER-localized complex of Dsl1p, Sec20p, and Tip20p functions in retrograde traffic, perhaps upstream of a Sly1p/Ufe1p complex. Last, we show that Dsl1p interacts with the δ-subunit of the retrograde COPI coat, Ret2p, and discuss possible roles for this interaction. PMID:11739780

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

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.

Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane.

PubMed

Römisch, K

1999-12-01

Misfolded secretory and transmembrane proteins are retained in the endoplasmic reticulum (ER) and subsequently degraded. Degradation is primarily mediated by cytosolic proteasomes and thus requires retrograde transport out of the ER back to the cytosol. The available evidence suggests that the protein-conducting channel formed by the Sec61 complex is responsible for both forward and retrograde transport of proteins across the ER membrane. For transmembrane proteins, retrograde transport can be viewed as a reversal of integration of membrane proteins into the ER membrane. Retrograde transport of soluble proteins through the Sec61 channel after signal-peptide cleavage, however, must be mechanistically distinct from signal-peptide-mediated import into the ER through the same channel.

Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway.

PubMed

Larios, Jorge A; Jausoro, Ignacio; Benitez, Maria-Luisa; Bronfman, Francisca C; Marzolo, Maria-Paz

2014-09-19

ApoER2 and the neurotrophin receptors Trk and p75(NTR) are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75(NTR) are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75(NTR) mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors. We found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75(NTR). Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF). Our results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.

Tomato Ribonuclease LX with the Functional Endoplasmic Reticulum Retention Motif HDEF Is Expressed during Programmed Cell Death Processes, Including Xylem Differentiation, Germination, and Senescence1

PubMed Central

Lehmann, Karin; Hause, Bettina; Altmann, Dorit; Köck, Margret

2001-01-01

We have studied the subcellular localization of the acid S-like ribonuclease (RNase) LX in tomato (Lycopersicon esculentum Mill.) cells using a combination of biochemical and immunological methods. It was found that the enzyme, unexpectedly excluded from highly purified vacuoles, accumulates in the endoplasmic reticulum. The evidence that RNase LX is a resident of the endoplasmic reticulum (ER) is supported by an independent approach showing that the C-terminal peptide HDEF of RNase LX acts as an alternative ER retention signal in plants. For functional testing, the cellular distribution of chimeric protein constructs based on a marker protein, Brazil nut (Bertholletia excelsa) 2S albumin, was analyzed immunochemically in transgenic tobacco (Nicotiana tabacum) plants. Here, we report that the peptide motif is necessary and sufficient to accumulate 2S albumin constructs of both vacuolar and extracellular final destinations in the ER. We have shown immunochemically that RNase LX is specifically expressed during endosperm mobilization and leaf and flower senescence. Using immunofluorescence, RNase LX protein was detected in immature tracheary elements, suggesting a function in xylem differentiation. These results support a physiological function of RNase LX in selective cell death processes that are also thought to involve programmed cell death. It is assumed that RNase LX accumulates in an ER-derived compartment and is released by membrane disruption into the cytoplasma of those cells that are intended to undergo autolysis. These processes are accompanied by degradation of cellular components supporting a metabolic recycling function of the intracellular RNase LX. PMID:11598219

Retention capacity of correlated surfaces.

PubMed

Schrenk, K J; Araújo, N A M; Ziff, R M; Herrmann, H J

2014-06-01

We extend the water retention model [C. L. Knecht et al., Phys. Rev. Lett. 108, 045703 (2012)] to correlated random surfaces. We find that the retention capacity of discrete random landscapes is strongly affected by spatial correlations among the heights. This phenomenon is related to the emergence of power-law scaling in the lake volume distribution. We also solve the uncorrelated case exactly for a small lattice and present bounds on the retention of uncorrelated landscapes.

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

Persistence-Retention. Snapshot™ Report, Spring 2014

ERIC Educational Resources Information Center

National Student Clearinghouse, 2014

2014-01-01

This snapshot report provides information on student persistence and retention rates for Spring 2014. Data is presented in tabular format on the following: (1) First-Year Persistence and Retention Rates by Starting Enrollment Intensity (all institutional sectors); (2) First-Year Persistence and Retention Rates by Age at College Entry (all…

[Retention and biomechanics of retentive complexes. 3. The Kratochvil school and current retentive complexes].

PubMed

Enrique Fernández, M; Jacques Grimonster, L

1989-04-01

The authors analyse the biomechanical bases of the Kratochvil "retentive complex" and show how they have induced the nowadays north-american propositions (RPI & RPA). They compare them to the european ones (Nally-Martinet).

Role of ER Export Signals in Controlling Surface Potassium Channel Numbers

NASA Astrophysics Data System (ADS)

Ma, Dzwokai; Zerangue, Noa; Lin, Yu-Fung; Collins, Anthony; Yu, Mei; Jan, Yuh Nung; Yeh Jan, Lily

2001-01-01

Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.

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

PubMed

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

2016-11-21

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

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

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

PubMed

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

2009-11-30

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

Persistence-Retention. Snapshot™ Report, Spring 2015

ERIC Educational Resources Information Center

National Student Clearinghouse, 2015

2015-01-01

This Snapshot Report offers information on student persistence and retention rates for 2009-2013. It offers data on the following: (1) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year Private Nonprofit Institutions; (2) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year…

"The nurse satisfaction, service quality and nurse retention chain": implications for management of recruitment and retention.

PubMed

Newman, Karin; Maylor, Uvanney; Chansarkar, Bal

2002-01-01

This paper presents the findings of a qualitative study, based on interviews with over 130 nurses and midwives in four London Trust hospitals on: the main factors influencing nurse satisfaction and retention; empirical support for the robustness of a conceptual framework or model "the nurse satisfaction, service quality and nurse retention chain"; and some managerial considerations for recruitment and retention. The three main factors influencing job satisfaction were patients, the inherent characteristics of nursing and the nursing team; the two main sources of job dissatisfaction were staff shortages and poor management and amongst nurse retention strategies improving working conditions was more important than increased pay. For recruitment, as well as retention, improving the image and reputation of nursing along with improvements in work-life balance were pre-requisites for meeting the challenging target of an additional 20,000 nurses on the wards by 2004.

The Successful Mobilization of a Campus Community for Student Retention. Report of the University Retention Steering Committee.

ERIC Educational Resources Information Center

Eastern Michigan Univ., Ypsilanti.

Components of a student retention program at Eastern Michigan University are examined; for each effort to improve retention, project objectives and design, results, and recommendations are presented. Retention initiatives, decided upon as a result of a campus-wide mobilization of effort, include: a student-focused orientation system, a fast track…

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

12 CFR 202.12 - Record retention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Record retention. 202.12 Section 202.12 Banks... OPPORTUNITY ACT (REGULATION B) § 202.12 Record retention. (a) Retention of prohibited information. A creditor...) Applications. For 25 months (12 months for business credit, except as provided in paragraph (b)(5) of this...

ER phospholipid composition modulates lipogenesis during feeding and in obesity.

PubMed

Rong, Xin; Wang, Bo; Palladino, Elisa Nd; de Aguiar Vallim, Thomas Q; Ford, David A; Tontonoz, Peter

2017-10-02

Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability.

Excitation mechanisms of Er optical centers in GaN epilayers

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

George, D. K.; Hawkins, M. D.; McLaren, M.

2015-10-26

We report direct evidence of two mechanisms responsible for the excitation of optically active Er{sup 3+} ions in GaN epilayers grown by metal-organic chemical vapor deposition. These mechanisms, resonant excitation via the higher-lying inner 4f shell transitions and band-to-band excitation of the semiconductor host, lead to narrow emission lines from isolated and the defect-related Er optical centers. However, these centers have different photoluminescence spectra, local defect environments, decay dynamics, and excitation cross sections. The photoluminescence at 1.54 μm from the isolated Er optical center which can be excited by either mechanism has the same decay dynamics, but possesses a much highermore » excitation cross-section under band-to-band excitation. In contrast, the photoluminescence at 1.54 μm from the defect-related Er optical center can only be observed through band-to-band excitation but has the largest excitation cross-section. These results explain the difficulty in achieving gain in Er doped GaN and indicate approaches for realization of optical amplification, and possibly lasing, at room temperature.« less

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.

Spectral properties of Er3+/Yb3+ codoped tungsten-tellurite glasses.

PubMed

Shen, Xiang; Nie, QiuHua; Xu, TieFeng; Gao, Yuan

2005-07-01

The spectral properties of Er3+/Yb3+ codoped tungsten-tellurite (WT) glasses have been investigated. The measured absorption spectra are analyzed by Judd-Ofelt theory. The compositional change of intensity parameter omega2 is attributed to the change in the covalency between the Er3+ and oxygen ions, the asymmetry in the local structures around the Er3+ ions can be neglected. The lifetimes of 4I(13/2) level of Er3+ in WT glasses are measured and comparable with other TeO2-based glasses. The stimulated emission cross-section is calculated based on McCumber theory. The fluorescence full width at half maximum (FWHM) and the emission cross-section (sigma(peak)) of the 4I(13/2) --> 4I(15/2) transition of Er3+ in different glass hosts have been compared. The suitability of such WT glasses as host materials for 1.5 microm broadband amplification is discussed.

Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy.

PubMed

Chen, Yong-Zi; Kim, Youngchul; Soliman, Hatem H; Ying, GuoGuang; Lee, Jae K

2018-06-01

ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER- patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER- breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER- breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC = 0.637, P  = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P  = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P  = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER- and TN subgroups (log-rank test P -value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER- breast cancer. © 2018 The authors.

Innate Sensing of Influenza A Virus Hemagglutinin Glycoproteins by the Host Endoplasmic Reticulum (ER) Stress Pathway Triggers a Potent Antiviral Response via ER-Associated Protein Degradation.

PubMed

Frabutt, Dylan A; Wang, Bin; Riaz, Sana; Schwartz, Richard C; Zheng, Yong-Hui

2018-01-01

Innate immunity provides an immediate defense against infection after host cells sense danger signals from microbes. Endoplasmic reticulum (ER) stress arises from accumulation of misfolded/unfolded proteins when protein load overwhelms the ER folding capacity, which activates the unfolded protein response (UPR) to restore ER homeostasis. Here, we show that a mechanism for antiviral innate immunity is triggered after the ER stress pathway senses viral glycoproteins. When hemagglutinin (HA) glycoproteins from influenza A virus (IAV) are expressed in cells, ER stress is induced, resulting in rapid HA degradation via proteasomes. The ER-associated protein degradation (ERAD) pathway, an important UPR function for destruction of aberrant proteins, mediates HA degradation. Three class I α-mannosidases were identified to play a critical role in the degradation process, including EDEM1, EDEM2, and ERManI. HA degradation requires either ERManI enzymatic activity or EDEM1/EDEM2 enzymatic activity when ERManI is not expressed, indicating that demannosylation is a critical step for HA degradation. Silencing of EDEM1, EDEM2, and ERManI strongly increases HA expression and promotes IAV replication. Thus, the ER stress pathway senses influenza HA as "nonself" or misfolded protein and sorts HA to ERAD for degradation, resulting in inhibition of IAV replication. IMPORTANCE Viral nucleic acids are recognized as important inducers of innate antiviral immune responses that are sensed by multiple classes of sensors, but other inducers and sensors of viral innate immunity need to be identified and characterized. Here, we used IAV to investigate how host innate immunity is activated. We found that IAV HA glycoproteins induce ER stress, resulting in HA degradation via ERAD and consequent inhibition of IAV replication. In addition, we have identified three class I α-mannosidases, EDEM1, EDEM2, and ERManI, which play a critical role in initiating HA degradation. Knockdown of these proteins

Retention of Emergency Care Knowledge.

ERIC Educational Resources Information Center

Burckes, Mardie E.; Shao, Kung Ping Pam

1984-01-01

Data on the emergency care knowledge of college students were measured by a pretest, posttest, and retention test. A high relationship was found between students' posttest scores and retention test scores. Findings are discussed. (Author/DF)

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

PubMed

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

2016-01-01

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

IRE1: ER stress sensor and cell fate executor.

PubMed

Chen, Yani; Brandizzi, Federica

2013-11-01

Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prevention and Treatment of ER-Negative Breast Cancer

DTIC Science & Technology

2005-10-01

human breast epithelial cell lines that express several levels of P13 kinase and AKT activity. These lines will be characterized with respect to...cancer. (4)Defined a putative role for psoriasin in breast tumor progression. (5) Progress in the analysis of the role of NFkappaB signaling in ER...press.. 9 PREVENTION AND TREATMENT OF ER-NEGATIVE BREAST CANCERPrincipal Investigator: Brown, Mvles A. 4) IGF-1 Receptor and the Akt protein kinase Akt

Predictors of home healthcare nurse retention.

PubMed

Ellenbecker, Carol Hall; Porell, Frank W; Samia, Linda; Byleckie, James J; Milburn, Michael

2008-01-01

To examine the level of job satisfaction and test a theoretical model of the direct and indirect effects of job satisfaction, and individual nurse and agency characteristics, on intent to stay and retention for home healthcare nurses. A descriptive correlation study of home healthcare nurses in six New England states. Home healthcare nurse job satisfaction self-report data was collected with the HHNJS survey questionnaire & Retention Survey Questionnaire. Based on a structural equation model, job tenure and job satisfaction were the strongest predictors of nurse retention. Understanding the variables associated with home healthcare nurse retention can help agencies retain nurses in a time of severe nurse shortages and increased patient demand. Predicted nursing shortages and increasing demand have made the retention of experienced, qualified nursing staff essential to assure access to high-quality home healthcare services in the future.

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

NASA Image and Video Library

1998-04-29

ER-2C tail number 809, was one of two Airborne Science ER-2Cs used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2Cs were 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-2C missions lasted about six hours with ranges of about 2,200 nautical miles. The aircraft typically flew at altitudes above 65,000 feet. On November 19, 1998, the ER-2C set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft was 63 feet long, with a wingspan of 104 feet. The top of the vertical tail was 16 feet above ground when the aircraft was on the bicycle-type landing gear. Cruising speeds were 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-2C.

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.

Apoptosis Induced by the UV Filter Benzophenone-3 in Mouse Neuronal Cells Is Mediated via Attenuation of Erα/Pparγ and Stimulation of Erβ/Gpr30 Signaling.

PubMed

Wnuk, A; Rzemieniec, J; Lasoń, W; Krzeptowski, W; Kajta, M

2018-03-01

Although benzophenone-3 (BP-3) has frequently been reported to play a role in endocrine disruption, there is insufficient data regarding the impact of BP-3 on the nervous system, including its possible adverse effects on the developing brain. Our study demonstrated that BP-3 caused neurotoxicity and activated apoptosis via an intrinsic pathway involving the loss of mitochondrial membrane potential and the activation of caspases-9 and -3 and kinases p38/MAPK and Gsk3β. These biochemical alterations were accompanied by ROS production, increased apoptotic body formation and impaired cell survival, and by an upregulation of the genes involved in apoptosis. The BP-3-induced effects were tissue-specific and age-dependent with the most pronounced effects observed in neocortical cells at 7 days in vitro. BP-3 changed the messenger RNA (mRNA) expression levels of Erα, Erβ, Gpr30, and Pparγ in a time-dependent manner. At 3 h of exposure, BP-3 downregulated estrogen receptor mRNAs but upregulated Pparγ mRNA. After prolonged exposures, BP-3 downregulated the receptor mRNAs except for Erβ mRNA that was upregulated. The BP-3-induced patterns of mRNA expression measured at 6 and 24 h of exposure reflected alterations in the protein levels of the receptors and paralleled their immunofluorescent labeling. Erα and Pparγ agonists diminished, but Erβ and Gpr30 agonists stimulated the BP-3-induced apoptotic and neurotoxic effects. Receptor antagonists caused the opposite effects, except for ICI 182,780. This is in line with a substantial reduction in the effects of BP-3 in cells with siRNA-silenced Erβ/Gpr30 and the maintenance of BP-3 effects in Erα- and Pparγ siRNA-transfected cells. We showed for the first time that BP-3-affected mRNA and protein expression levels of Erα, Erβ, Gpr30, and Pparγ, paralleled BP-3-induced apoptosis and neurotoxicity. Therefore, we suggest that BP-3-evoked apoptosis of neuronal cells is mediated via attenuation of Erα/Pparγ and

Lockheed ER-2 high altitude research aircraft in flight

NASA Image and Video Library

1997-11-04

ER-2 tail number 706, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

Pilot James Barrilleaux with ER-2 aircraft on ramp

NASA Image and Video Library

1998-03-18

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-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

PubMed

Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

2016-10-01

Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. Copyright © 2016 the American Physiological Society.

Retention of iron by infants.

PubMed

Fomon, S J; Nelson, S E; Ziegler, E E

2000-01-01

Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or (59)Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.

5 CFR 575.306 - Authorizing a retention incentive.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Authorizing a retention incentive. 575... RECRUITMENT, RELOCATION, AND RETENTION INCENTIVES; SUPERVISORY DIFFERENTIALS; AND EXTENDED ASSIGNMENT INCENTIVES Retention Incentives § 575.306 Authorizing a retention incentive. (a) Authority of authorized...

Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER.

PubMed

Kannan, Muthukumar; Lahiri, Sujoy; Liu, Li-Ka; Choudhary, Vineet; Prinz, William A

2017-03-01

Close contacts between organelles, often called membrane contact sites (MCSs), are regions where lipids are exchanged between organelles. Here, we identify a novel mechanism by which cells promote phospholipid exchange at MCSs. Previous studies have shown that phosphatidylserine (PS) synthase activity is highly enriched in portions of the endoplasmic reticulum (ER) in contact with mitochondria. The objective of this study was to determine whether this enrichment promotes PS transport out of the ER. We found that PS transport to mitochondria was more efficient when PS synthase was fused to a protein in the ER at ER-mitochondria contacts than when it was fused to a protein in all portions of the ER. Inefficient PS transport to mitochondria was corrected by increasing tethering between these organelles. PS transport to endosomes was similarly enhanced by PS production in regions of the ER in contact with endosomes. Together, these findings indicate that PS production at MCSs promotes PS transport out of the ER and suggest that phospholipid production at MCSs may be a general mechanism of channeling lipids to specific cellular compartments.

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

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

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

Azarov, Alexander; Galeckas, Augustinas; Kuznetsov, Andrej

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 Ermore » 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.« less

IMG ER: a system for microbial genome annotation expert review and curation.

PubMed

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

2009-09-01

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.

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

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

Antonson, P., E-mail: per.antonson@ki.se; Omoto, Y.; Humire, P.

2012-08-10

Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established amore » new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.« less

The effects of energy transfer on the Er3+ 1.54 μm luminescence in nanostructured Y2O3 thin films with heterogeneously distributed Yb3+ and Er3+ codopants

NASA Astrophysics Data System (ADS)

Hoang, J.; Schwartz, Robert N.; Wang, Kang L.; Chang, J. P.

2012-09-01

We report the effects of heterogeneous Yb3+ and Er3+ codoping in Y2O3 thin films on the 1535 nm luminescence. Yb3+:Er3+:Y2O3 thin films were deposited using sequential radical enhanced atomic layer deposition. The Yb3+ energy transfer was investigated for indirect and direct excitation of the Yb 2F7/2 state using 488 nm and 976 nm sources, respectively, and the trends were described in terms of Forster and Dexter's resonant energy transfer theory and a macroscopic rate equation formalism. The addition of 11 at. % Yb resulted in an increase in the effective Er3+ photoluminescence (PL) yield at 1535 nm by a factor of 14 and 42 under 488 nm and 976 nm excitations, respectively. As the Er2O3 local thickness was increased to greater than 1.1 Å, PL quenching occurred due to strong local Er3+ ↔ Er3+ excitation migration leading to impurity quenching centers. In contrast, an increase in the local Yb2O3 thickness generally resulted in an increase in the effective Er3+ PL yield, except when the Er2O3 and Yb2O3 layers were separated by more than 2.3 Å or were adjacent, where weak Yb3+ ↔ Er3+ coupling or strong Yb3+ ↔ Yb3+ interlayer migration occurred, respectively. Finally, it is suggested that enhanced luminescence at steady state was observed under 488 nm excitation as a result of Er3+ → Yb3+ energy back transfer coupled with strong Yb3+ ↔ Yb3+ energy migration.

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

PubMed Central

Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

2014-01-01

Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

ApoER2 and VLDLR in the developing human telencephalon.

PubMed

Cheng, Lin; Tian, Zhiliang; Sun, Ruizhen; Wang, Zhendong; Shen, Jingling; Shan, Zhiyan; Jin, Lianhong; Lei, Lei

2011-07-01

The Reelin-Dab1 signaling pathway plays a crucial role in regulating the migration and position of cortical neurons during the development of the cerebral cortex. Mutation in Reelin may result in severe developmental disorders such as autosomal recessive lissencephaly. Apolipoprotein E receptor type-2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are canonical receptors of Reelin, through which extracellular Reelin activates the intracellular adapter, Disabled1(Dab1), and subsequently interacts with other molecules. Although it is widely accepted that ApoER2 and VLDLR are indispensable components of the Reelin signaling pathway, little is known of their expression pattern in the laminated developing human brain. Here, we collected 18 cases of human fetal brains of 6-18 gestational weeks (GW) old and examined the expression of ApoER2 and VLDLR in the their telencephalon using immunocytochemical staining. We found that both receptors were absent in the preplate (PP) and the earliest stage of the cortical plate (CP). In later stages of CP development, ApoER2 was expressed earlier than VLDLR in the migrating neurons. Thus, the Reelin-Dab1 signaling pathway may not be involved in the formation of the preplate and deep layers of the CP. Instead, the pathway may act on neurons that are destined to form the more superficial layers of the CP. In addition, the pathway required ApoER2 only rather than both ApoER2 and VLDLR at the initiation of activity. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Fractionated Er:YAG laser versus fully ablative Er:YAG laser for scar revision: Results of a split scar, double blinded, prospective trial.

PubMed

Tidwell, W James; Owen, Cindy E; Kulp-Shorten, Carol; Maity, Abhishek; McCall, Michael; Brown, Timothy S

2016-11-01

Ablative laser resurfacing is a common treatment for post-surgical scars. Fractional ablative laser resurfacing has been an emerging treatment option that is replacing fully ablative lasers in many applications. Data comparing fractionated and fully ablative lasers in treating post-operative scars are lacking. Twenty patients were enrolled in a split scar study following excisions from dermatologic surgery. Wounds had to be older than 8 weeks but less than 1 year. The scars were randomly divided into two halves. One half of the scar was treated with fully ablative erbium-doped yttrium aluminum garnet (Er:YAG) and the other was treated with fractionated Er:YAG. The scars were treated at monthly intervals for 3 months, then followed up at months 1 and 2 after the last treatment. POSAS was used to evaluate the scars by a panel of dermatologists blinded to the lasers in conjunction with the patients, who were also blinded. Physicians and patients both observed a superior outcome of 32.5% (P = 0.019) and 58.1% (P = 0.001), respectively, using the POSAS. There was no trend in difference in pain reported by the patient between the two lasers. Patients overwhelmingly preferred the fractionated Er:YAG laser (94%) to the fully ablative laser when asked at the end of the study. Although this study is limited by a short follow-up period, it shows a statistically significant superior outcome in fractionated Er:YAG over fully ablative Er:YAG for scar revision. It also adds quantitative values to the assessment of scar appearance when treated with fractionated lasers compared to fully ablative lasers. It was also found that the fractionated Er:YAG had increased patient satisfaction, but there was no difference in reported pain scores. These data are useful when counseling patients undergoing laser surgery. Lasers Surg. Med. 48:837-843, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

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).

Optimization of ELISA Conditions to Quantify Colorectal Cancer Antigen-Antibody Complex Protein (GA733-FcK) Expressed in Transgenic Plant

PubMed Central

Ahn, Junsik; Lee, Kyung Jin

2014-01-01

The purpose of this study is to optimize ELISA conditions to quantify the colorectal cancer antigen GA733 linked to the Fc antibody fragment fused to KDEL, an ER retention motif (GA733-FcK) expressed in transgenic plant. Variable conditions of capture antibody, blocking buffer, and detection antibody for ELISA were optimized with application of leaf extracts from transgenic plant expressing GA733-FcK. In detection antibody, anti-EpCAM/CD362 IgG recognizing the GA733 did not detect any GA733-FcK whereas anti-human Fc IgG recognizing the human Fc existed in plant leaf extracts. For blocking buffer conditions, 3% BSA buffer clearly blocked the plate, compared to the 5% skim-milk buffer. For capture antibody, monoclonal antibody (MAb) CO17-1A was applied to coat the plate with different amounts (1, 0.5, and 0.25 μg/well). Among the amounts of the capture antibody, 1 and 0.5 μg/well (capture antibody) showed similar absorbance, whereas 0.25 μg/well of the capture antibody showed significantly less absorbance. Taken together, the optimized conditions to quantify plant-derived GA733-FcK were 0.5 μg/well of MAb CO17-1A per well for the capture antibody, 3% BSA for blocking buffer, and anti-human Fc conjugated HRP. To confirm the optimized ELISA conditions, correlation analysis was conducted between the quantified amount of GA733-FcK in ELISA and its protein density values of different leaf samples in Western blot. The co-efficient value R2 between the ELISA quantified value and protein density was 0.85 (p<0.01), which indicates that the optimized ELISA conditions feasibly provides quantitative information of GA733-FcK expression in transgenic plant. PMID:24555929

Antihypertensive activity of transgenic rice seed containing an 18-repeat novokinin peptide localized in the nucleolus of endosperm cells.

PubMed

Wakasa, Yuhya; Zhao, Hui; Hirose, Sakiko; Yamauchi, Daiki; Yamada, Yuko; Yang, Lijun; Ohinata, Kousaku; Yoshikawa, Masaaki; Takaiwa, Fumio

2011-09-01

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp, RPLKPW) is a new potent antihypertensive peptide based on the sequence of ovokinin (2-7) derived from ovalbumin. We previously generated transgenic rice seeds in which eight novokinin were fused to storage protein glutelins (GluA2 and GluC) for expression. Oral administration of these seeds to spontaneously hypertensive rats (SHRs) reduced systolic blood pressures at a dose of 1 g seed/kg of SHR. Here, 10- or 18-tandem repeats of novokinin with an endoplasmic reticulum (ER) retention signal (Lys-Asp-Glu-Leu, KDEL) at the C terminus were directly expressed in rice under the control of the glutelin promoter containing its signal peptide. Only small amounts of the 18-repeat novokinin accumulated, and it was unexpectedly deposited in the nucleolus. This abnormal intracellular localization was explained by an endogenous signal for nuclear localization. The GFP reporter protein fused to this sequence targeted to nuclei by a transient assay using onion epidermal cells. Transgenic seed expressing the 18-repeat novokinin exhibited significantly higher antihypertensive activity after a single oral dose to SHR even at one-quarter the amount (0.25 g/kg) of the transgenic rice seed expressing the fusion construct; though, its novokinin content was much lower (1/5). Furthermore, in a long-term administration for 5 weeks, even a smaller dose (0.0625 g/kg) of transgenic seeds could confer antihypertensive activity. This high antihypertensive activity may be attributed to differences in digestibility of expressed products by gastrointestinal enzymes and the unique intracellular localization. These results indicate that accumulation of novokinin as a tandemly repeated structure in transgenic rice is more effective than as a fusion-type structure. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.

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

PubMed

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

2010-04-01

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

Structural, optical and dielectric studies of Er substituted zinc ferrite nanospheres

NASA Astrophysics Data System (ADS)

Shoba, M.; Kaleemulla, S.

2017-12-01

The cationic distributions among tetrahedral and octahedral sites in spinel ferrites have a profound influence on their properties. Many studies were reported with various transition metal (TM) and rare earth (RE) cations distribution. We report the synthesis, structural, morphology, lattice vibrational, optical and dielectric properties of heavy RE cation (Er) substituted ZnFe2O4 as a function of different experimental parameters. The coprecipitated and calcined ZnFe2-xErxO4 (x = 0, 0.2, 0.4, 0.6 & 0.8) compounds crystallizes in cubic spinel structure and show narrow particle size distribution due to surfactant PEG. Particle size reduces (27-16 nm) with enhance of Er concentration (x = 0 to 0.8) in the compounds. The EDAX spectra of the samples incorporation Er3+ ions into the lattice and the cubic lattice parameter enhances with Er3+ concentration. The lattice vibrational spectra reveal that the particles surface were free from surfactant PEG. Optical excitation studies show that energy band gap (Eg) of compounds reduces (1.85-2.00 eV) with enhance of Er concentration. The temperature, as well as frequency dependent dielectric constant (εrʹ) of ZnFe2-xErxO4, shows enhanced εrʹ with Er concentration up to x = 0.4 and then reduces with further enhancing of Er concentration. The dielectric loss factor (εrʹʹ) show similar variation with Er concentration. Further, both εrʹ and εrʹʹ were reduced with enhancing of field frequency. In addition, both εrʹ and εrʹʹ were enhanced with temperature and showed exponential change at low frequencies and high temperature and is attributed magnetic transition at around 525 K. The interface polarization mechanism is the predominant one in the present samples. The ac impedance spectra show two semicircles and each semicircle results from dielectric relaxation due to either particle (grain) or particles interface (grain boundary) polarization. The ac impedance reduces with enhancing of temperature. From the above

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

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

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 presencemore » 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.« less

The ER-mitochondria interface: the social network of cell death.

PubMed

Grimm, Stefan

2012-02-01

When cellular organelles communicate bad things can happen. Recent findings uncovered that the junction between the endoplasmic reticulum (ER) and the mitochondria holds a crucial role for cell death regulation. Not only does this locale connect the two best-known organelles in apoptosis, numerous regulators of cell death are concentrated at this spot, providing a terrain for intense signal transfers. Ca2+ is the most prominent signalling factor that is released from the ER and, at high concentration, mediates the transfer of an apoptosis signal to mitochondria as the executioner organelle for cell death. An elaborate array of checks and balances is fine-tuning this process including Bcl-2 family members. Moreover, MAMs, "mitochondria-associated membranes", are distinct membrane sections at the ER that are in close contact with mitochondria and have been found to exchange lipids and lipid-derived molecules such as ceramide for apoptosis induction. Recent work has also described a reverse transfer of apoptosis signals, from mitochondria to the ER, via cytochrome c release and prolonged IP3R opening or through the mitochondrial fission factor Fis1 and Bap31 at the ER, which form the ARCosome, a novel caspase-activation complex. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Ga flux dependence of Er-doped GaN luminescent thin films

NASA Astrophysics Data System (ADS)

Lee, D. S.; Steckl, A. J.

2002-02-01

Er-doped GaN thin films have been grown on (111) Si substrates with various Ga fluxes in a radio frequency plasma molecular beam epitaxy system. Visible photoluminescence (PL) and electroluminescence (EL) emission at 537/558 nm and infrared (IR) PL emission at 1.5 μm from GaN:Er films exhibited strong dependence on the Ga flux. Both visible and IR PL and visible EL increase with the Ga flux up to the stoichiometric growth condition, as determined by growth rate saturation. Beyond this condition, all luminescence levels abruptly dropped to the detection limit with increasing Ga flux. The Er concentration, measured by secondary ion mass spectroscopy and Rutherford backscattering, decreases with increasing Ga flux under N-rich growth conditions and remains constant above the stoichiometric growth condition. X-ray diffraction indicated that the crystalline quality of the GaN:Er film was improved with increasing Ga flux up to stoichiometric growth condition and then saturated. Er ions in the films grown under N-rich conditions appear much more optically active than those in the films grown under Ga-rich conditions.

Fecal retention in childhood: Evaluation on ultrasonography.

PubMed

Hatori, Reiko; Tomomasa, Takeshi; Ishige, Takashi; Tatsuki, Maiko; Arakawa, Hirokazu

2017-04-01

To assess the usefulness of rectal diameter measurement on ultrasonography as a diagnostic tool for fecal retention in children. One hundred children (median age, 5.0 years), consisting of 80 with functional constipation and 20 without constipation, participated in the study. All patients underwent physical examination that included digital rectal examination. Forty-five children underwent ultrasonography in three differential planes: transection above the symphysis; under the ischial spine; and at the bladder neck. The measurement of the rectal diameter at the transection above the symphysis could most easily detect fecal retention and had the closest correlations with retention among the three planes. Rectal diameter was wider at all measuring points (35.2 vs 20.9 mm above the symphysis, P < 0.0001; 35.7 vs 24.0 mm under the ischial spine, P < 0.0001; and 19.4 vs 8.7 mm at the bladder neck, P < 0.0001) in children with fecal retention than in those with no fecal retention. With regard to presence of constipation, children with fecal retention had a wider rectal diameter above the symphysis than those with no fecal retention (children with functional constipation, 35.3 vs 20.0 mm, P < 0.0001; children without constipation: 32.6 vs 14.6 mm, P = 0.0026). The cut-off for the rectal diameter measured above the symphysis to identify fecal retention was 27 mm, with high sensitivity and specificity (95.5% and 94.1%, respectively). Ultrasound rectal diameter measurement can be used to detect fecal retention in children. © 2016 Japan Pediatric Society.

Exocrine pancreas ER stress is differentially induced by different fatty acids.

PubMed

Danino, Hila; Ben-Dror, Karin; Birk, Ruth

2015-12-10

Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

Data Retention and Anonymity Services

NASA Astrophysics Data System (ADS)

Berthold, Stefan; Böhme, Rainer; Köpsell, Stefan

The recently introduced legislation on data retention to aid prosecuting cyber-related crime in Europe also affects the achievable security of systems for anonymous communication on the Internet. We argue that data retention requires a review of existing security evaluations against a new class of realistic adversary models. In particular, we present theoretical results and first empirical evidence for intersection attacks by law enforcement authorities. The reference architecture for our study is the anonymity service AN.ON, from which we also collect empirical data. Our adversary model reflects an interpretation of the current implementation of the EC Directive on Data Retention in Germany.

Carboxymethyl- and carboxyl-catechins from ripe Pu-er tea.

PubMed

Tian, Li-Wen; Tao, Mu-Ke; Xu, Min; Hu, Jing; Zhu, Hong-Tao; Xiong, Wen-Yong; Wang, Dong; Yang, Chong-Ren; Zhang, Ying-Jun

2014-12-17

Ripe Pu-er tea, a special microbial postfermented tea originated from Yunnan Province, China, since ancient times, is made from green Pu-er tea prepared from the leaves of Camellia sinensis var. assamica (Theaceae). Chemical investigation on thearubigin (n-BuOH-soluble) fraction of the commercial ripe Pu-er tea, led to the identification of four new flavan-3-ol derivatives, 8-carboxymethyl-(+)-catechin (1), 8-carboxymethyl-(+)-catechin methyl ester (2), 6-carboxymethyl-(+)-catechin (3), and 6-carboxyl-(-)-gallocatechin (4), together with 18 known compounds, including other three flavan-3-ol derivatives (5-7), 10 flavonoid glycosides (8-17), two hydrolyzable tannins (18 and 19), two quinic acid derivatives (20-21), and a purine alkaloid (22). Flavonoid glycosides 8-11 are reported from tea plants for the first time. The thearubigin fraction of ripe Pu-er tea was qualitatively analyzed by HPLC, and gallic acid was found to be the major component. Compounds 4, 6-17, 21 and 22 were tested for their acute activities on insulin sensitivity in differentiated 3T3-L1 adipocytes, but none of them showed significant bioactivity at a concentration of 10 μM.

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

PubMed

Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

2017-09-07

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

20 CFR 655.167 - Document retention requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Document retention requirements. 655.167... retention requirements. (a) Entities required to retain documents. All employers filing an Application for... retain the documents and records proving compliance with this subpart. (b) Period of required retention...

Molecular Mechanisms Controlling GLUT4 Intracellular Retention

PubMed Central

Blot, Vincent

2008-01-01

In basal adipocytes, glucose transporter 4 (GLUT4) is sequestered intracellularly by an insulin-reversible retention mechanism. Here, we analyze the roles of three GLUT4 trafficking motifs (FQQI, TELEY, and LL), providing molecular links between insulin signaling, cellular trafficking machinery, and the motifs in the specialized trafficking of GLUT4. Our results support a GLUT4 retention model that involves two linked intracellular cycles: one between endosomes and a retention compartment, and the other between endosomes and specialized GLUT4 transport vesicles. Targeting of GLUT4 to the former is dependent on the FQQI motif and its targeting to the latter is dependent on the TELEY motif. These two motifs act independently in retention, with the TELEY-dependent step being under the control of signaling downstream of the AS160 rab GTPase activating protein. Segregation of GLUT4 from endosomes, although positively correlated with the degree of basal retention, does not completely account for GLUT4 retention or insulin-responsiveness. Mutation of the LL motif slows return to basal intracellular retention after insulin withdrawal. Knockdown of clathrin adaptin protein complex-1 (AP-1) causes a delay in the return to intracellular retention after insulin withdrawal. The effects of mutating the LL motif and knockdown of AP-1 were not additive, establishing that AP-1 regulation of GLUT4 trafficking requires the LL motif. PMID:18550797

Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.

PubMed

Henis-Korenblit, Sivan; Zhang, Peichuan; Hansen, Malene; McCormick, Mark; Lee, Seung-Jae; Cary, Michael; Kenyon, Cynthia

2010-05-25

When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Growth of semimetallic ErAs films epitaxially embedded in GaAs

NASA Astrophysics Data System (ADS)

Crook, Adam M.; Nair, Hari P.; Lee, Jong H.; Ferrer, Domingo A.; Akinwande, Deji; Bank, Seth R.

2011-10-01

We present models for the growth and electrical conductivity of ErAs films grown with the nanoparticle-seeded film growth technique. This growth mode overcomes the mismatch in rotational symmetry between the rocksalt ErAs crystal structure and the zincblende GaAs crystal structure. This results in films of ErAs grown through a thin film of GaAs that preserves the symmetry of the substrate. The conductivity of the films, as a function of film thickness, are investigated and a surface roughness model is used to explain observed trends. Transmission electron micrographs confirm the suppression of anti-phase domains. A simple diffusion model is developed to describe the diffusion and incorporation of surface erbium into subsurface ErAs layers and predict potential failure mechanisms of the growth method.

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.

Heat effect of pulsed Er:YAG laser radiation

NASA Astrophysics Data System (ADS)

Hibst, Raimund; Keller, Ulrich

1990-06-01

Pulsed Er:YAG laser radiation has been found to be effective for dental enamel and dentin removal. Damage to the surrounding hard tissue is little, but before testing the Er:YAG laser clinically for the preparation of cavities, possible effects on the soft tissue of the pulp must be known. In order to estimate pulp damage , temperature rise in dentin caused by the laser radiation was measured by a thermocouple. Additionally, temperature distributions were observed by means of a thermal imaging system. The heat effect of a single Er:YAG laser pulse is little and limited to the vicinity of the impact side. Because heat energy is added with each additional pulse , the temperature distribution depends not only on the radiant energy, but also on the number of pulses and the repetition rate. Both irradiation conditions can be found , making irreversible pulp damage either likely or unlikely. The experimental observations can be explained qualitatively by a simple model of the ablation process.

Toward a Political Explanation of Grade Retention

ERIC Educational Resources Information Center

Bali, Valentina A.; Anagnostopoulos, Dorothea; Roberts, Reginald

2005-01-01

Policies that mandate in-grade retention of low-performing students have become central components of standards-based reforms across the country. While educational researchers have extensively studied the student-level correlates of retention and the consequences of retention for student achievement, little attention has been focused on…

A parametric study of helium retention in beryllium and its effect on deuterium retention

NASA Astrophysics Data System (ADS)

Alegre, D.; Baldwin, M. J.; Simmonds, M.; Nishijima, D.; Hollmann, E. M.; Brezinsek, S.; Doerner, R. P.

2017-12-01

Beryllium samples have been exposed in the PISCES-B linear plasma device to conditions relevant to the International Thermonuclear Experimental Reactor (ITER) in pure He, D, and D/He mixed plasmas. Except at intermediate sample exposure temperatures (573-673 K) He addition to a D plasma is found to have a beneficial effect as it reduces the D retention in Be (up to ˜55%), although the mechanism is unclear. Retention of He is typically around 1020-1021 He m-2, and is affected primarily by the Be surface temperature during exposition, by the ion fluence at <500 K exposure, but not by the ion impact energy at 573 K. Contamination of the Be surface with high-Z elements from the mask of the sample holder in pure He plasmas is also observed under certain conditions, and leads to unexpectedly large He retention values, as well as changes in the surface morphology. An estimation of the tritium retention in the Be first wall of ITER is provided, being sufficiently low to allow a safe operation of ITER.

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

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

2013-05-07

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.

DoSSiER: Database of scientific simulation and experimental results

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

Wenzel, Hans; Yarba, Julia; Genser, Krzystof

The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientific Simulation and Experimental Results) is being developed as a central repository to store the simulation results as well as the experimental data used for validation. DoSSiER can be easily accessed via a web application. In addition, a web service allows for programmatic access to the repository to extract records in json or xml exchange formats. In this paper, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

DoSSiER: Database of scientific simulation and experimental results

DOE PAGES

Wenzel, Hans; Yarba, Julia; Genser, Krzystof; ...

2016-08-01

The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientific Simulation and Experimental Results) is being developed as a central repository to store the simulation results as well as the experimental data used for validation. DoSSiER can be easily accessed via a web application. In addition, a web service allows for programmatic access to the repository to extract records in json or xml exchange formats. In this paper, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

40 CFR 160.195 - Retention of records.

Code of Federal Regulations, 2012 CFR

2012-07-01

... obtained from mutagenicity tests, specimens of soil, water, and plants, and wet specimens of blood, urine... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Retention of records. 160.195 Section... LABORATORY PRACTICE STANDARDS Records and Reports § 160.195 Retention of records. (a) Record retention...

40 CFR 160.195 - Retention of records.

Code of Federal Regulations, 2014 CFR

2014-07-01

... obtained from mutagenicity tests, specimens of soil, water, and plants, and wet specimens of blood, urine... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Retention of records. 160.195 Section... LABORATORY PRACTICE STANDARDS Records and Reports § 160.195 Retention of records. (a) Record retention...

40 CFR 160.195 - Retention of records.

Code of Federal Regulations, 2013 CFR

2013-07-01

... obtained from mutagenicity tests, specimens of soil, water, and plants, and wet specimens of blood, urine... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Retention of records. 160.195 Section... LABORATORY PRACTICE STANDARDS Records and Reports § 160.195 Retention of records. (a) Record retention...

40 CFR 160.195 - Retention of records.

Code of Federal Regulations, 2011 CFR

2011-07-01

... obtained from mutagenicity tests, specimens of soil, water, and plants, and wet specimens of blood, urine... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Retention of records. 160.195 Section... LABORATORY PRACTICE STANDARDS Records and Reports § 160.195 Retention of records. (a) Record retention...

Reframing Retention Strategy: A Focus on Progress

ERIC Educational Resources Information Center

Spittle, Brian

2013-01-01

Few words have dominated the vocabulary of college retention as has the word "persistence." Many institutions still struggle to engage faculty and administrators in building campuswide retention efforts, to find the organizational levers that translate the abstractions and complexities of retention theory into scalable and durable initiatives, and…

22 CFR 50.20 - Retention of nationality.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Retention of nationality. 50.20 Section 50.20 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS NATIONALITY PROCEDURES Retention and Resumption of Nationality § 50.20 Retention of nationality. (a) Section 351(b) of the Immigration and...

22 CFR 50.20 - Retention of nationality.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Retention of nationality. 50.20 Section 50.20 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS NATIONALITY PROCEDURES Retention and Resumption of Nationality § 50.20 Retention of nationality. (a) Section 351(b) of the Immigration and...

22 CFR 50.20 - Retention of nationality.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Retention of nationality. 50.20 Section 50.20 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS NATIONALITY PROCEDURES Retention and Resumption of Nationality § 50.20 Retention of nationality. (a) Section 351(b) of the Immigration and...

22 CFR 50.20 - Retention of nationality.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Retention of nationality. 50.20 Section 50.20 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS NATIONALITY PROCEDURES Retention and Resumption of Nationality § 50.20 Retention of nationality. (a) Section 351(b) of the Immigration and...

22 CFR 50.20 - Retention of nationality.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Retention of nationality. 50.20 Section 50.20 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS NATIONALITY PROCEDURES Retention and Resumption of Nationality § 50.20 Retention of nationality. (a) Section 351(b) of the Immigration and...

46 CFR 308.600 - Records retention requirement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Records retention requirement. 308.600 Section 308.600 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Records Retention § 308.600 Records retention requirement. The records specified in §§ 308.8, 308.517, and...

46 CFR 308.600 - Records retention requirement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 8 2012-10-01 2012-10-01 false Records retention requirement. 308.600 Section 308.600 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Records Retention § 308.600 Records retention requirement. The records specified in §§ 308.8, 308.517, and...

46 CFR 308.600 - Records retention requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Records retention requirement. 308.600 Section 308.600 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Records Retention § 308.600 Records retention requirement. The records specified in §§ 308.8, 308.517, and...

46 CFR 308.600 - Records retention requirement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false Records retention requirement. 308.600 Section 308.600 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Records Retention § 308.600 Records retention requirement. The records specified in §§ 308.8, 308.517, and...

46 CFR 308.600 - Records retention requirement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Records retention requirement. 308.600 Section 308.600 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE Records Retention § 308.600 Records retention requirement. The records specified in §§ 308.8, 308.517, and...

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

PubMed

Hayashi, Teruo; Su, Tsung-Ping

2007-11-02

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

The influence of pressure changes on the retentive force and coronal microleakage of different types of posts in endodontically treated teeth during simulated dives.

PubMed

Mitov, Gergo; Draenert, Florian; Schumann, Paul; Stötzer, Marcus; von See, Constantin

2016-12-01

We assessed the influence of a simulated diving environment on the interfacial microleakage and retentive forces of different post types in root-canal-filled teeth. One-hundred-and-twenty extracted, single-rooted teeth were endodontically treated and were randomly divided into three groups according to the post and cement used: ER Post/Harvard cement (Titanium), CeraPost/DentinBuild Evo (Zirconia), DT Light Post/Calibra (FRC). Each group was randomly divided into two equal subgroups, a control group, and an experimental group, subjected to simulated dives to 456 kPa in a diving chamber. For 10 specimens of each subgroup the pull-out strength and the coronal microleakage were measured. Significant differences in the linear coronal penetration were observed between the Titanium and FRC groups (experimental group P ≤ 0.001; control group P = 0.02). Diving simulation had no significant impact on the microleakage for the three post types. The FRC groups showed significantly higher retentive strength values compared to the Titanium and Zirconia groups before and after simulated diving. The pull-out strength of the titanium experimental group was significantly less than the control group (P = 0.008). Following root canal treatment the combination of fibre-reinforced posts and resin cement should be preferred for patients requiring retention for tooth restorations using posts that are likely to be exposed to hyperbaric conditions.

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer.

PubMed

Pinhel, Isabel; Hills, Margaret; Drury, Suzanne; Salter, Janine; Sumo, Georges; A'Hern, Roger; Bliss, Judith M; Sestak, Ivana; Cuzick, Jack; Barrett-Lee, Peter; Harris, Adrian; Dowsett, Mitch

2012-03-14

Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors. ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts. ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease. Clinical trial identifier: ISRCTN31514446.

ER-2 High Altitude Solar Cell Calibration Flights

NASA Technical Reports Server (NTRS)

Piszczor, Michael F.

2017-01-01

ER-2 Capability: Flights can be conducted once every one to two days during a campaign. Flight season runs from April through September. Twelve 2x2cm cells can be flown per flight, or any other configuration that fits inside of the 14.2x14.2cm illuminated area. This capacity could be doubled if the second ER-2 pod is used. Data supplied includes Isc, Voc, IV curve, and cell temperature. Other optical or atmospheric sensors can be flown as able.

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

PubMed Central

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

Reframing Retention Strategy: A Focus on Profile

ERIC Educational Resources Information Center

Kalsbeek, David H.; Zucker, Brian

2013-01-01

Over 35 years of retention theory and literature have acknowledged the importance of institutional and student profiles in accounting for cross-sectional differences in retention and completion rates between types of colleges and universities. The first "P" within a 4 Ps framework of student retention--"profile"--recognizes that an institution's…

Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes

PubMed Central

Yang, Mei; Omura, Satoshi; Bonifacino, Juan S.; Weissman, Allan M.

1998-01-01

Expression of the T cell antigen receptor (TCR) on the surface of thymocytes and mature T cells is dependent on the assembly of receptor subunits into TCRs in the endoplasmic reticulum (ER) and their successful traversal of the secretory pathway to the plasma membrane. TCR subunits that fail to exit the ER for the Golgi complex are degraded by nonlysosomal processes that have been referred to as “ER degradation”. The molecular basis for the loss of the TCR CD3-δ and TCR-α subunits from the ER was investigated in lymphocytes. For CD3-δ, we describe a process leading to its degradation that includes trimming of mannose residues from asparagine-linked (N-linked) oligosaccharides, generation of ubiquitinated membrane-bound intermediates, and proteasome-dependent removal from the ER membrane. When either mannosidase activity or the catalytic activity of proteasomes was inhibited, loss of CD3-δ was markedly curtailed and CD3-δ remained membrane bound in a complex with CD3-ε. TCR-α was also found to be degraded in a proteasome-dependent manner with ubiquitinated intermediates. However, no evidence of a role for mannosidases was found for TCR-α, and significant retrograde movement through the ER membrane took place even when proteasome function was inhibited. These findings provide new insights into mechanisms employed to regulate levels of TCRs, and underscore that cells use multiple mechanisms to target proteins from the ER to the cytosol for degradation. PMID:9500786

Optical properties of Er 3+/Yb 3+-codoped transparent PLZT ceramic

NASA Astrophysics Data System (ADS)

Zheng, Zhiqiang; Li, Xiaoyan; Liu, Jing; Feng, Zhuohong; Li, Baozeng; Yang, Jiwen; Li, Kewen; Jiang, Hua; Chen, Xuesheng; Xie, Jianping; Ming, Hai

2008-01-01

Optical absorption and emission spectra of Er 3+/Yb 3+ ions in PLZT (Pb 1-xLa xZr yTi 1-yO 3) ceramic have been studied. Based on the Judd-Ofelt (J-O) theory, the J-O intensity parameters were calculated to be Ω2=2.021×10 -20 cm 2, Ω4=0.423×10 -20 cm 2, Ω6=0.051×10 -20 cm 2 from the absorption spectrum of Er 3+/Yb 3+-codoped PLZT. The J-O intensity parameters have been used to calculate the radiative lifetimes and the branching ratios for some excited 4I 13/2, 4I 11/2, 4I 9/24F 9/2, and 4S 3/2 levels of Er 3+ ion. The stimulated emission cross-section (8.24×10 -21 cm 2) was evaluated for the 4I 13/2→ 4I 15/2 transition of Er 3+. The upconversion emissions at 538, 564, and 666 nm have been observed in Er 3+/Yb 3+-codoped PLZT by exciting at 980 nm, and their origins were identified and analyzed.

Er-doped YVO4 amplifier diode pumped at 976 nm

NASA Astrophysics Data System (ADS)

Newburgh, G. A.; Dubinskii, Mark

2016-05-01

We report on the use of a 976 nm diode pumped Er:YVO4 slab for the amplification of 1603 nm laser radiation with a small signal gain of 2.1. To the best of our knowledge, this represents the first use of Er:YVO4 as a non-resonantly pumped amplifier.

Hormonal Resistance And Metastasis ER-Coregulartor-Src Signaling Targeted Therapy

DTIC Science & Technology

2011-09-01

with STAT3 and cross-talk between ER~ and STAT3 play an important role in leptin -in- duced STAT3 activation’’ The II.Kl axis is the major signaling...cancer. These patients could be treated with an aromatase inhibitor (Letrozole) that ablates peripheral estrogen synthesis and ER degraders /signaling

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

Highly scalable, resonantly cladding-pumped, Er-doped fiber laser with record efficiency.

PubMed

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

2009-05-15

We report the performance of a resonantly cladding-pumped, Yb-free, Er-doped fiber laser. We believe this is the first reported resonantly cladding-pumped fiber-Bragg-grating-based, Er-doped, large-mode-area (LMA) fiber laser. The laser, pumped by fiber-coupled InGaAsP/InP laser diode modules at 1,532.5 nm, delivers approximately 48 W of cw output at 1,590 nm. It is believed to be the highest power ever reported from a Yb-free Er-doped LMA fiber. This fully integrated laser also has the optical-to-optical efficiency of approximately 57%, to the best of our knowledge, the highest efficiency reported for cladding-pumped unidirectionally emitting Er-doped laser.

Antigen Retrieval to Improve the Immunocytochemistry Detection of Sigma-1 Receptors and ER Chaperones

PubMed Central

Hayashi, Teruo; Lewis, Abasha; Hayashi, Eri; Betenbaugh, Michael J.; Su, Tsung-Ping

2011-01-01

Molecular chaperones localized at the endoplasmic reticulum (ER) lumen constitutively or cellular stress-dependently associate with a variety of proteins to promote their proper folding or to inhibit protein misfolding. ER chaperones preferentially form large complexes with co-chaperones and/or misfolded proteins in a highly crowded cellular environment that often hampers their detection by immunocytochemistry (ICC). This study establishes an antigen retrieval (AR) protocol to improve the ICC detection of ER chaperones in cultured cells using widely available antibodies against synthetic peptides. Among ten different antigen retrieval/fixation conditions, only the AR with Tris-HCl (pH 9.5) containing 6 M urea (80 °C for 10 min) significantly improved the ICC detection of the novel ER chaperone sigma-1 receptor (Sig-1R) in Chinese hamster ovary cells. Extended fixation with 4% paraformaldehyde for 1 hr effectively preserved the morphology of the ER under the AR condition. This method greatly enhanced the signal-to-noise ratio in Sig-1R ICC, thus allowing for semi-quantitative detection of protein upregulation under ER stress. The AR similarly improved the ICC detection of a series of other major ER chaperones, including BiP/GRP78, GRP94, calnexin, calreticulin, ERp57, protein disulfide isomerase, and cyclophilin B. The improved ICC methodology using the urea AR at 80°C may improve ICC of ER molecules as well as visualization of ER structure and substructures. PMID:21573736

20 CFR 655.1319 - Document retention requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Document retention requirements. 655.1319... Employment in the United States (H-2A Workers) § 655.1319 Document retention requirements. (a) Entities... retention. Records and documents must be retained for a period of 3 years from the date of certification of...

ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence

PubMed Central

Miyazaki, Taiga; Kohno, Shigeru

2014-01-01

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence. PMID:24335436

Irreversibility and critical current density of FeSr2ErCu2O6+y

NASA Astrophysics Data System (ADS)

Hata, Y.; Iida, I.; Mochiku, T.; Yasuoka, H.

2018-03-01

FeSr2ErCu2O6+y (ErFe1212) and non-superconducting FeSr2ErCu1.9Zn0.1O6+y were synthesized to study the property of the superconductivity and the irreversibility of ErFe1212. A large irreversibility in the temperature dependence of magnetization and a hysteresis in the magnetization curve were observed in ErFe1212. By comparison with non-superconducting FeSr2ErCu1.9Zn0.1O6+y, it was found that the most part of the hysteresis at high magnetic eld originates from the magnetism of Fe ion and some part of the hysteresis at low magnetic eld originates from the superconductivity. Using the magnetization curve of ErFe1212 and FeSr2ErCu1.9Zn0.1O6+y, the J c of ErFe1212 in individual grains at 10 K under 0.1 T was estimated by the Bean model and {J}\\text{c}\\text{intra} was 2.6 × 109 A/m2. The critical current density across inter-grain boundaries at 10 K estimated by V ‑ I measurement was {J}\\text{c}\\text{intra} = 5.7 × 104 A/m2. A large difference between {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} was observed in ErFe1212. {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} of ErFe1212 are 2.2 and 5.2 times larger than these of YFe1212, respectively.

Analysis of the Glass-Forming Ability of Fe-Er Alloys, Based on Thermodynamic Modeling

NASA Astrophysics Data System (ADS)

Arutyunyan, N. A.; Zaitsev, A. I.; Dunaev, S. F.; Kalmykov, K. B.; El'nyakov, D. D.; Shaposhnikov, N. G.

2018-05-01

The Fe-Er phase diagram and thermodynamic properties of all its phases are assessed by means of self-consistent analysis. To refine the data on phase equilibria in the Fe-Er system, an investigation is performed in the 10-40 at % range of Er concentrations. The temperature-concentration dependences of the thermodynamic properties of a melt are presented using the model of ideal associated solutions. Thermodynamic parameters of each phase are obtained, and the calculated results are in agreement with available experimental data. The correlation between the thermodynamic properties of liquid Fe-Er alloys and their tendency toward amorphization are studied. It is shown that compositions of amorphous alloys prepared by melt quenching coincide with the ranges of concentration with the predominance of Fe3Er and FeEr2 associative groups that have large negative entropies of formation.

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

PubMed Central

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-01-01

ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

PubMed

Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

2016-08-02

Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

HPLC retention thermodynamics of grape and wine tannins.

PubMed

Barak, Jennifer A; Kennedy, James A

2013-05-08

The effect of grape and wine tannin structure on retention thermodynamics under reversed-phase high-performance liquid chromatography conditions on a polystyrene divinylbenzene column was investigated. On the basis of retention response to temperature, an alternative retention factor was developed to approximate the combined temperature response of the complex, unresolvable tannin mixture. This alternative retention factor was based upon relative tannin peak areas separated by an abrupt change in solvent gradient. Using this alternative retention factor, retention thermodynamics were calculated. Van't Hoff relationships of the natural log of the alternative retention factor against temperature followed Kirchoff's relationship. An inverse quadratic equation was fit to the data, and from this the thermodynamic parameters for tannin retention were calculated. All tannin fractions exhibited exothermic, spontaneous interaction, with enthalpy-entropy compensation observed. Normalizing for tannin size, distinct tannin compositional effects on thermodynamic parameters were observed. The results of this study indicate that HPLC can be valuable for measuring the thermodynamics of tannin interaction with a hydrophobic surface and provides a potentially valuable alternative to calorimetry. Furthermore, the information gathered may provide insight into understanding red wine astringency quality.

Soil Water Retention Curve

NASA Astrophysics Data System (ADS)

Johnson, L. E.; Kim, J.; Cifelli, R.; Chandra, C. V.

2016-12-01

Potential water retention, S, is one of parameters commonly used in hydrologic modeling for soil moisture accounting. Physically, S indicates total amount of water which can be stored in soil and is expressed in units of depth. S can be represented as a change of soil moisture content and in this context is commonly used to estimate direct runoff, especially in the Soil Conservation Service (SCS) curve number (CN) method. Generally, the lumped and the distributed hydrologic models can easily use the SCS-CN method to estimate direct runoff. Changes in potential water retention have been used in previous SCS-CN studies; however, these studies have focused on long-term hydrologic simulations where S is allowed to vary at the daily time scale. While useful for hydrologic events that span multiple days, the resolution is too coarse for short-term applications such as flash flood events where S may not recover its full potential. In this study, a new method for estimating a time-variable potential water retention at hourly time-scales is presented. The methodology is applied for the Napa River basin, California. The streamflow gage at St Helena, located in the upper reaches of the basin, is used as the control gage site to evaluate the model performance as it is has minimal influences by reservoirs and diversions. Rainfall events from 2011 to 2012 are used for estimating the event-based SCS CN to transfer to S. As a result, we have derived the potential water retention curve and it is classified into three sections depending on the relative change in S. The first is a negative slope section arising from the difference in the rate of moving water through the soil column, the second is a zero change section representing the initial recovery the potential water retention, and the third is a positive change section representing the full recovery of the potential water retention. Also, we found that the soil water moving has traffic jam within 24 hours after finished first

28 CFR 345.67 - Retention of benefits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... INDUSTRIES (FPI) INMATE WORK PROGRAMS Inmate Pay and Benefits § 345.67 Retention of benefits. (a) Job retention. Ordinarily, when an inmate is absent from the job for a significant period of time, the SOI will... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Retention of benefits. 345.67 Section 345...

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

Fracture Forces of Dentin after Surface Treatment with High Speed Drill Compared to Er:YAG and Er,Cr:YSGG Laser Irradiation

PubMed Central

Franzen, Rene; Kianimanesh, Nasrin; Marx, Rudolf; Ahmed, Asma; Gutknecht, Norbert

2016-01-01

Dental tooth restorative procedures may weaken the structural integrity of the tooth, with the possibility of leading to fracture. In this study we present findings of coronal dentin strength after different techniques of surface modification. The fracture strength of dentin beams after superficial material removal with a fine diamond bur high speed drill hand piece, Er:YAG (2.94 μm, 8 J/cm2), and Er,Cr:YSGG (2.78 μm, 7.8 J/cm2) laser irradiation slightly above the ablation threshold was measured by a four-point bending apparatus. Untreated dentin beams served as a control. A total of 58 dentin beams were manufactured from sterilized human extracted molars using the coronal part of the available dentin. Mean values of fracture strength were calculated as 82.0 ± 27.3 MPa for the control group (n = 10), 104.5 ± 26.3 MPa for high speed drill treatment (n = 10), 96.1 ± 28.1 MPa for Er,Cr:YSGG laser irradiation (n = 20), and 89.1 ± 36.3 MPa for Er:YAG laser irradiation (n = 18). Independent Student's t-tests showed no significant difference between each two groups (p > 0.05). Within the parameter settings and the limits of the experimental setup used in this study, both lasers systems as well as the high speed drill do not significantly weaken coronal dentin after surface treatment. PMID:26962473

Novel word retention in bilingual and monolingual speakers

PubMed Central

Kan, Pui Fong; Sadagopan, Neeraja

2014-01-01

The goal of this research was to examine word retention in bilinguals and monolinguals. Long-term word retention is an essential part of vocabulary learning. Previous studies have documented that bilinguals outperform monolinguals in terms of retrieving newly-exposed words. Yet, little is known about whether or to what extent bilinguals are different from monolinguals in word retention. Participants were 30 English-speaking monolingual adults and 30 bilingual adults who speak Spanish as a home language and learned English as a second language during childhood. In a previous study (Kan et al., 2014), the participants were exposed to the target novel words in English, Spanish, and Cantonese. In this current study, word retention was measured a week after the fast mapping task. No exposures were given during the one-week interval. Results showed that bilinguals and monolinguals retain a similar number of words. However, participants produced more words in English than in either Spanish or Cantonese. Correlation analyses revealed that language knowledge plays a role in the relationships between fast mapping and word retention. Specifically, within- and across-language relationships between bilinguals' fast mapping and word retention were found in Spanish and English, by contrast, within-language relationships between monolinguals' fast mapping and word retention were found in English and across-language relationships between their fast mapping and word retention performance in English and Cantonese. Similarly, bilinguals differed from monolinguals in the relationships among the word retention scores in three languages. Significant correlations were found among bilinguals' retention scores. However, no such correlations were found among monolinguals' retention scores. The overall findings suggest that bilinguals' language experience and language knowledge most likely contribute to how they learn and retain new words. PMID:25324789

Novel word retention in bilingual and monolingual speakers.

PubMed

Kan, Pui Fong; Sadagopan, Neeraja

2014-01-01

The goal of this research was to examine word retention in bilinguals and monolinguals. Long-term word retention is an essential part of vocabulary learning. Previous studies have documented that bilinguals outperform monolinguals in terms of retrieving newly-exposed words. Yet, little is known about whether or to what extent bilinguals are different from monolinguals in word retention. Participants were 30 English-speaking monolingual adults and 30 bilingual adults who speak Spanish as a home language and learned English as a second language during childhood. In a previous study (Kan et al., 2014), the participants were exposed to the target novel words in English, Spanish, and Cantonese. In this current study, word retention was measured a week after the fast mapping task. No exposures were given during the one-week interval. Results showed that bilinguals and monolinguals retain a similar number of words. However, participants produced more words in English than in either Spanish or Cantonese. Correlation analyses revealed that language knowledge plays a role in the relationships between fast mapping and word retention. Specifically, within- and across-language relationships between bilinguals' fast mapping and word retention were found in Spanish and English, by contrast, within-language relationships between monolinguals' fast mapping and word retention were found in English and across-language relationships between their fast mapping and word retention performance in English and Cantonese. Similarly, bilinguals differed from monolinguals in the relationships among the word retention scores in three languages. Significant correlations were found among bilinguals' retention scores. However, no such correlations were found among monolinguals' retention scores. The overall findings suggest that bilinguals' language experience and language knowledge most likely contribute to how they learn and retain new words.

Urinary Retention

MedlinePlus

... urinary retention with • bladder drainage • urethral dilation • urethral stents • prostate medications • surgery The type and length of ... patient will receive sedation and regional anesthesia. Urethral Stents Another treatment for urethral stricture involves inserting an ...

Lockheed ER-2 #709 high altitude research aircraft in flight

NASA Image and Video Library

1998-03-02

ER-2 tail number 709, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

Strategies for improving employee retention.

PubMed

Verlander, Edward G; Evans, Martin R

2007-03-28

This article proposes a solution to the perennial problem of talent retention in the clinical laboratory. It includes the presentation of 12 strategies that may be used to significantly improve institutional identity formation and establishment of the psychological contract that employees form with laboratory management. Identity formation and psychological contracting are deemed as essential in helping reduce employee turnover and increase retention. The 12 conversational strategies may be used as a set of best practices for all employees, but most importantly for new employees, and should be implemented at the critical moment when employees first join the laboratory. This time is referred to as "retention on-boarding"--the period of induction and laboratory orientation. Retention on-boarding involves a dialogue between employees and management that is focused on the psychological, practical, cultural, and political dimensions of the laboratory. It is placed in the context of the modern clinical laboratory, which is faced with employing and managing Generation X knowledge workers. Specific topics and broad content areas of those conversations are outlined.

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

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

Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito

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.more » 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.« less

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

PubMed Central

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

2016-01-01

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

Effect of water on dental material ablation of the Er:YAG laser

NASA Astrophysics Data System (ADS)

Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

1994-09-01

It is understood that if a laser is to replace the dental high speed handpiece it must be able to ablate dental materials which are present in teeth being treated with the laser. It is the intent of this paper to evaluate the effects of the Er:YAG laser on dental composite restorative material concentrating on the etch rate with and without waterspray. Composite dental material is used to form plugs of known thickness and the etch rate of the Er:YAG laser on this material is determined. The results are compared with those obtained from studies of the Er:YAG on dentin and enamel. In these studies the water reduced the efficiency of the Er:YAG laser 15 - 20% on these tissues.

phosphorus retention data and metadata

EPA Pesticide Factsheets

phosphorus retention in wetlands data and metadataThis dataset is associated with the following publication:Lane , C., and B. Autrey. Phosphorus retention of forested and emergent marsh depressional wetlands in differing land uses in Florida, USA. Wetlands Ecology and Management. Springer Science and Business Media B.V;Formerly Kluwer Academic Publishers B.V., GERMANY, 24(1): 45-60, (2016).

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

Disulfide bonds in ER protein folding and homeostasis

PubMed Central

Feige, Matthias J.; Hendershot, Linda M.

2010-01-01

Proteins that are expressed outside the cell must be synthesized, folded and assembled in a way that ensures they can function in their designate location. Accordingly these proteins are primarily synthesized in the endoplasmic reticulum (ER), which has developed a chemical environment more similar to that outside the cell. This organelle is equipped with a variety of molecular chaperones and folding enzymes that both assist the folding process, while at the same time exerting tight quality control measures that are largely absent outside the cell. A major post-translational modification of ER-synthesized proteins is disulfide bridge formation, which is catalyzed by the family of protein disulfide isomerases. As this covalent modification provides unique structural advantages to extracellular proteins, multiple pathways to their formation have evolved. However, the advantages that disulfide bonds impart to these proteins come at a high cost to the cell. Very recent reports have shed light on how the cell can deal with or even exploit the side reactions of disulfide bond formation to maintain homeostasis of the ER and its folding machinery. PMID:21144725

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

EPA Science Inventory

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

Synergism between a half-site and an imperfect estrogen-responsive element, and cooperation with COUP-TFI are required for estrogen receptor (ER) to achieve a maximal estrogen-stimulation of rainbow trout ER gene.

PubMed

Petit, F G; Métivier, R; Valotaire, Y; Pakdel, F

1999-01-01

In all oviparous, liver represents one of the main E2-target tissues where estrogen receptor (ER) constitutes the key mediator of estrogen action. The rainbow trout estrogen receptor (rtER) gene expression is markedly up-regulated by estrogens and the sequences responsible for this autoregulation have been located in a 0.2 kb upstream transcription start site within - 40/- 248 enhancer region. Absence of interference with steroid hormone receptors and tissue-specific factors and a conserved basal transcriptional machinery between yeast and higher eukaryotes, make yeast a simple assay system that will enable determination of important cis-acting regulatory sequences within rtER gene promoter and identification of transcription factors implicated in the regulation of this gene. Deletion analysis allowed to show a synergistic effect between an imperfect estrogen-responsive element (ERE) and a consensus half-ERE to achieve a high hormone-dependent transcriptional activation of the rtER gene promoter in the presence of stably expressed rtER. As in mammalian cells, here we observed a positive regulation of the rtER gene promoter by the chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) through enhancing autoregulation. Using a point mutation COUP-TFI mutant unable to bind DNA demonstrates that enhancement of rtER gene autoregulation requires the interaction of COUP-TFI to the DNA. Moreover, this enhancement of transcriptional activation by COUP-TFI requires specifically the AF-1 transactivation function of ER and can be observed in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384. Thus, this paper describes the reconstitution of a hormone-responsive transcription unit in yeast in which the regulation of rtER gene promoter could be enhanced by the participation of cis-elements and/or trans-acting factors, such as ER itself or COUP-TF.

Considering Student Retention as a Complex System: A Possible Way forward for Enhancing Student Retention

ERIC Educational Resources Information Center

Forsman, Jonas; van den Bogaard, Maartje; Linder, Cedric; Fraser, Duncan

2015-01-01

This study uses multilayer minimum spanning tree analysis to develop a model for student retention from a complex system perspective, using data obtained from first-year engineering students at a large well-regarded institution in the European Union. The results show that the elements of the system of student retention are related to one another…

Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease

PubMed Central

Seltzer, Ben

2010-01-01

An extended release form of the cholinesterase inhibitor (ChEI) drug galantamine (galantamine-ER) was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer’s disease (AD). Except for predicted differences in (Cmax) and tmax, comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR), are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24) showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs. PMID:20169037

Sensory-Neuropathy-Causing Mutations in ATL3 Cause Aberrant ER Membrane Tethering.

PubMed

Krols, Michiel; Detry, Sammy; Asselbergh, Bob; Almeida-Souza, Leonardo; Kremer, Anna; Lippens, Saskia; De Rycke, Riet; De Winter, Vicky; Müller, Franz-Josef; Kurth, Ingo; McMahon, Harvey T; Savvides, Savvas N; Timmerman, Vincent; Janssens, Sophie

2018-05-15

The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro, these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity but are unable to promote membrane fusion, suggesting a defect in an intermediate step of the ATL3 functional cycle. Our data show that the effects of ATL3 mutations on ER network organization go beyond a loss of fusion and shed light on neuropathies caused by atlastin defects. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Optimization of loading ratio of ErN as regenerator of 4K-GM cryocooler

NASA Astrophysics Data System (ADS)

Nakagawa, T.; Miyauchi, T.; Shiraishi, T.; Seino, S.; Yamamoto, T. A.; Fujimoto, Y.; Masuyama, S.

2017-09-01

High purity erbium nitride (ErN) spheres with the size range of 150-180 µm and 180-212 µm were prepared by nitriding Er metal spheres with low oxygen content. The initial regenerator material of HoCu2 on the cold end of the second regenerator column in 4K-GM cryocooler with nominal cooling power of 0.1 W at 4.2 K was replaced by ErN with different sizes. Higher cooling power was obtained when ErN of smaller size with lower oxygen content was used. We investigated the effect of partial replacement of HoCu2 by ErN in the cold end side of second stage regenerator column on cooling power of 4K-GM cryocoolers. When ErN were substituted for 20 % of HoCu2, the cooling power at 4.2 K reached 0.318 W. This value was 1.36 times as high as that of the cooling power of the GM cryocooler with commercially available regenerator arrangement. Therefore, use of ErN regenerator materials leads to the energy-saving and downsizing of 4K-GM cryocoolers.

Employee retention: a customer service approach.

PubMed

Gerson, Richard F

2002-01-01

Employee retention is a huge problem. There are staff shortages in radiology because not enough people are entering the profession; too many people are leaving the profession for retirement, higher-paying jobs or jobs with less stress; and there are not enough opportunities for career advancement. Staff shortages are exacerbated by difficulty in retaining people who enter the profession. While much work has been focused on recruitment and getting more people "in the front door," I suggest that the bulk of future efforts be focused on employee retention and "closing the back door." Employee retention must be an ongoing process, not a program. Approaches to employee retention that focus on external things, i.e., things that the company can do to or for the employee, generally are not successful. The truth is that employee retention processes must focus on what the employee gets out of the job. The process must be a benefits-based approach that helps employees answer the question, "What's in it for me?" The retention processes must be ongoing and integrated into the daily culture of the company. The best way to keep your employees is to treat them like customers. Customer service works for external customers. We treat them nicely. We work to satisfy them. We help them achieve their goals. Why not do the same for our employees? If positive customer service policies and practices can satisfy and keep external customers, why not adapt these policies and practices for employees? And, there is a service/satisfaction link between employee retention and higher levels of customer satisfaction. Customers prefer dealing with the same employees over and over again. Employee turnover destroys a customer's confidence in the company. Just like a customer does not want to have to "train and educate" a new provider, they do not want to do the same for your "revolving door" employees. So, the key is to keep employees so they in turn will help you keep your customers. Because the

Hydrogen retention in lithium and lithium oxide films

NASA Astrophysics Data System (ADS)

Buzi, L.; Yang, Y.; Domínguez-Gutiérrez, F. J.; Nelson, A. O.; Hofman, M.; Krstić, P. S.; Kaita, R.; Koel, B. E.

2018-04-01

Pure lithium (Li) surfaces are difficult to maintain in fusion devices due to rapid oxide formation, therefore, parameterizing and understanding the mechanisms of hydrogen (H, D) retention in lithium oxide (Li2O) in addition to pure Li is crucial for Li plasma-facing material applications. To compare H retention in Li and Li2O films, measurements were made as a function of surface temperature (90-520 K) under ultrahigh vacuum (UHV) conditions using temperature programmed desorption (TPD). In both cases, the total retention dropped with surface temperature, from 95% at 90 K to 35% at 520 K Li2O films retained H in similar amounts as pure Li. Molecular Dynamics (MD) modeling was used to elucidate the mechanisms of H retention, and results were consistent with experiments in terms of both retention fraction and the drop of retention with temperature.

Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

PubMed Central

Xu, Jiqian; Hu, Houxiang; Chen, Bin; Yue, Rongchuan; Zhou, Zhou; Liu, Yin; Zhang, Shuang; Xu, Lei; Wang, Huan; Yu, Zhengping

2015-01-01

Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes. PMID:26291709

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

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

PubMed

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

ER-driven membrane contact sites: Evolutionary conserved machineries for stress response and autophagy regulation?

PubMed Central

Molino, Diana; Nascimbeni, Anna Chiara; Giordano, Francesca; Codogno, Patrice

2017-01-01

ABSTRACT Endoplasmic Reticulum (ER), spreading in the whole cell cytoplasm, is a central player in eukaryotic cell homeostasis, from plants to mammals. Beside crucial functions, such as membrane lipids and proteins synthesis and outward transport, the ER is able to connect to virtually every endomembrane compartment by specific tethering molecular machineries, which enables the establishment of membrane-membrane contact sites. ER-mitochondria contact sites have been shown to be involved in autophagosome biogenesis, the main organelle of the autophagy degradation pathway. More recently we demonstrated that also ER-plasma membrane contact sites are sites for autophagosomes assembly, suggesting that more generally ER-organelles contacts are involved in autophagy and organelle biogenesis. Here we aim to discuss the functioning of ER-driven contact sites in mammals and plants and more in particular emphasize on their recently highlighted function in autophagy to finally conclude on some key questions that may be useful for further research in the field. PMID:29259731

Hydrogeology of the Umm Er Radhuma Aquifer (Arabian peninsula)

NASA Astrophysics Data System (ADS)

Dirks, Heiko; Al Ajmi, Hussain; Kienast, Peter; Rausch, Randolf

2018-03-01

The aim of this article is to enhance the understanding of the Umm Er Radhuma aquifer's genesis, and its hydraulic and hydrochemical development over time. This is a prerequisite for wise use of the fossil groundwater resources contained within. The Umm Er Radhuma is a karstified limestone aquifer, extending over 1.6 Mio. km2 in the eastern part of the Arabian Peninsula. Both epigene and hypogene karstification contributed to the genesis of what is today the most prolific aquifer in the region. Besides man-made abstractions, even the natural outflows are higher than the small recharge (natural storage depletion). The Umm Er Radhuma shows that large aquifers in arid regions are never in "steady state" (where inflows equal outflows), considering Quaternary climate history. The aquifer's adaption to climate changes (precipitation, sea level) can be traced even after thousands of years, and is slower than the climate changes themselves.

The ER Contact Proteins VAPA/B Interact with Multiple Autophagy Proteins to Modulate Autophagosome Biogenesis.

PubMed

Zhao, Yan G; Liu, Nan; Miao, Guangyan; Chen, Yong; Zhao, Hongyu; Zhang, Hong

2018-04-23

The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation. Depletion of VAPs impairs progression of IMs into autophagosomes. Upon autophagy induction, VAPs are recruited to autophagosome formation sites on the ER, a process mediated by their interactions with FIP200 and PI(3)P. VAPs directly interact with FIP200 and ULK1 through their conserved FFAT motifs and stabilize the ULK1/FIP200 complex at the autophagosome formation sites on the ER. The formation of ULK1 puncta is significantly reduced by VAPA/B depletion. VAPs also interact with WIPI2 and enhance the formation of the WIPI2/FIP200 ER/IM tethering complex. Depletion of VMP1, which increases the ER/IM contact, greatly elevates the interaction of VAPs with these autophagy proteins. The VAPB P56S mutation, which is associated with amyotrophic lateral sclerosis, reduces the ULK1/FIP200 interaction and impairs autophagy at an early step, similar to the effect seen in VAPA/B-depleted cells. Our study reveals that VAPs directly interact with multiple ATG proteins, thereby contributing to ER/IM contact formation for autophagosome biogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

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...

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

Unusual hafnium-pyridylamido/ER(n) heterobimetallic adducts (ER(n) = ZnR2 or AlR3).

PubMed

Rocchigiani, Luca; Busico, Vincenzo; Pastore, Antonello; Talarico, Giovanni; Macchioni, Alceo

2014-02-17

NMR spectroscopy and DFT studies indicate that the Symyx/Dow Hf(IV)-pyridylamido catalytic system for olefin polymerization, [{N(-),N,CNph(-)}HfMe][B(C6F5)4] (1, Nph = naphthyl), interacts with ER(n) (E = Al or Zn, R = alkyl group) to afford unusual heterobimetallic adducts [{N(-),N}HfMe(μ-CNph)(μ-R)ER(n-1)][B(C6F5)4 in which the cyclometalated Nph acts as a bridge between Hf and E. (1)H VT (variable-temperature) EXSY NMR spectroscopy provides direct evidence of reversible alkyl exchanges in heterobimetallic adducts, with ZnR2 showing a higher tendency to participate in this exchange than AlR3. 1-Hexene/ERn competitive reactions with 1 at 240 K reveal that the formation of adducts is strongly favored over 1-hexene polymerization. Nevertheless, a slight increase in the temperature (to >265 K) initiates 1-hexene polymerization. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Water retention curve for hydrate-bearing sediments

NASA Astrophysics Data System (ADS)

Dai, Sheng; Santamarina, J. Carlos

2013-11-01

water retention curve plays a central role in numerical algorithms that model hydrate dissociation in sediments. The determination of the water retention curve for hydrate-bearing sediments faces experimental difficulties, and most studies assume constant water retention curves regardless of hydrate saturation. This study employs network model simulation to investigate the water retention curve for hydrate-bearing sediments. Results show that (1) hydrate in pores shifts the curve to higher capillary pressures and the air entry pressure increases as a power function of hydrate saturation; (2) the air entry pressure is lower in sediments with patchy rather than distributed hydrate, with higher pore size variation and pore connectivity or with lower specimen slenderness along the flow direction; and (3) smaller specimens render higher variance in computed water retention curves, especially at high water saturation Sw > 0.7. Results are relevant to other sediment pore processes such as bioclogging and mineral precipitation.

Photoluminescence of Er-doped silicon-rich oxide thin films with high Al concentrations

NASA Astrophysics Data System (ADS)

Rozo, Carlos; Fonseca, Luis F.; Jaque, Daniel; García Solé, José

Er-doped silicon-rich oxide (SRO) thin films co-doped with Al in high concentrations were prepared by sputtering. Some films were deposited using a substrate heater (150 °CEr ion emission presents variations as the O content decreases and the Al content increases. The dependence of the Er ion 980 nm peak PL with respect to the Er ion 1525 nm peak PL indicates that the first emission depends less on energy transfer upconversion (ETU) processes as the O content decreases and the Al content increases. Broadband excitable Er3+ infrared (IR) emission with less loss due to ETU processes is important for applications in photonics.

Silicide formation process of Er films with Ta and TaN capping layers.

PubMed

Choi, Juyun; Choi, Seongheum; Kim, Jungwoo; Na, Sekwon; Lee, Hoo-Jeong; Lee, Seok-Hee; Kim, Hyoungsub

2013-12-11

The phase development and defect formation during the silicidation reaction of sputter-deposited Er films on Si with ∼20-nm-thick Ta and TaN capping layers were examined. TaN capping effectively prevented the oxygen incorporation from the annealing atmosphere, which resulted in complete conversion to the ErSi2-x phase. However, significant oxygen penetration through the Ta capping layer inhibited the ErSi2-x formation, and incurred the growth of several Er-Si-O phases, even consuming the ErSi2-x layer formed earlier. Both samples produced a number of small recessed defects at an early silicidation stage. However, large rectangular or square-shaped surface defects, which were either pitlike or pyramidal depending on the capping layer identity, were developed as the annealing temperature increased. The origin of different defect generation mechanisms was suggested based on the capping layer-dependent silicidation kinetics.

A Cost Benefit Analysis Between the Current Naval Officer Retention Bonus Plan and the Enlisted Retention Bonus Plan

DTIC Science & Technology

2016-06-01

that personnel targeted for retention had a direct ability to affect the success of the transaction and company. High potential, job function, job level...and job title rounded out the top five reasons personnel were targeted for retention . In brief, this study found that slightly more than half of...lower income may value the job security provided by service in the military, thus making retention in the military a more attractive option. 4

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.

5 CFR 950.604 - Records retention.

Code of Federal Regulations, 2011 CFR

2011-01-01

... VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.604 Records retention. Federations, PCFOs and other... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Records retention. 950.604 Section 950.604 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS...

5 CFR 950.604 - Records retention.

Code of Federal Regulations, 2013 CFR

2013-01-01

... VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.604 Records retention. Federations, PCFOs and other... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Records retention. 950.604 Section 950.604 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS...

5 CFR 950.604 - Records retention.

Code of Federal Regulations, 2014 CFR

2014-01-01

... VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.604 Records retention. Federations, PCFOs and other... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Records retention. 950.604 Section 950.604 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS...

5 CFR 950.604 - Records retention.

Code of Federal Regulations, 2012 CFR

2012-01-01

... VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.604 Records retention. Federations, PCFOs and other... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Records retention. 950.604 Section 950.604 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS...

5 CFR 950.604 - Records retention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.604 Records retention. Federations, PCFOs and other... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Records retention. 950.604 Section 950.604 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS...

A successful Minority Retention Project.

PubMed

Gardner, Janelle D

2005-12-01

Racial and ethnic minorities are underrepresented in the nursing profession. The high attrition rate of minority students from nursing schools contributes to this problem. Academic leaders are calling for change in nursing education and asking educators to work diligently to retain minority students. This article describes a Minority Retention Project that included interventions designed to enhance the integration of minority students into a supportive learning environment, assist them in using the available resources, and help them feel connected and supported by their peers and faculty. At the end of the first year of the project, the nursing school experienced 100% retention of minority nursing students. Increasing the retention and graduation of minority nursing students supports the continued effort to provide culturally competent health care.

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.

The interaction between ER and NFκB in resistance to endocrine therapy

PubMed Central

2012-01-01

Endocrine therapy is a commonly used treatment for estrogen receptor (ER)-positive breast cancer. Although endocrine therapy has a favorable outcome in many patients, development of resistance is common. Recent studies have shown that NFκB, a transcription factor regulating a wide variety of cellular processes, might play a role in the development of endocrine resistance. The precise interaction between ER and NFκB and how this contributes to the attenuated responsiveness of ER-positive breast cancer cells to hormonal treatment remains unclear. This review provides an overview of the mechanisms of action for both transcription factors and focuses on the current knowledge explaining how ER and NFκB affect each other's activity and how this cross-talk might contribute to the development of an endocrine resistance phenotype in breast cancer cells. PMID:22963717

Newly Licensed RN Retention: Hospital and Nurse Characteristics.

PubMed

Blegen, Mary A; Spector, Nancy; Lynn, Mary R; Barnsteiner, Jane; Ulrich, Beth T

2017-10-01

The aims of this study were to examine the relationship between 1-year retention of newly licensed RNs (NLRNs) employed in hospitals and personal and hospital characteristics, and determine which characteristics had the most influence. A secondary analysis of data collected in a study of transition to practice was used to describe the retention of 1464 NLRNs employed by 97 hospitals in 3 states. Hospitals varied in size, location (urban and rural), Magnet® designation, and university affiliation. The NLRNs also varied in education, age, race, gender, and experience. The overall retention rate at 1 year was 83%. Retention of NLRNs was higher in urban areas and in Magnet hospitals. The only personal characteristic that affected retention was age, with younger nurses more likely to stay. Hospital characteristics had a larger effect on NLRN retention than personal characteristics. Hospitals in rural areas have a particular challenge in retaining NLRNs.

Hydrogen retention in lithium and lithium oxide films

DOE PAGES

Buzi, L.; Yang, Y.; Dominguez-Gutierrez, F. J.; ...

2018-02-09

Pure lithium (Li) surfaces are difficult to maintain in fusion devices due to rapid oxide formation, therefore, parameterizing and understanding the mechanisms of hydrogen (H, D) retention in lithium oxide (Li 2O) in addition to pure Li is crucial for Li plasma-facing material applications. To compare H retention in Li and Li 2O films, measurements were made as a function of surface temperature (90–520 K) under ultrahigh vacuum (UHV) conditions using temperature programmed desorption (TPD). In both cases, the total retention dropped with surface temperature, from 95% at 90 K to 35% at 520 K Li 2O films retained Hmore » in similar amounts as pure Li. Finally, Molecular Dynamics (MD) modeling was used to elucidate the mechanisms of H retention, and results were consistent with experiments in terms of both retention fraction and the drop of retention with temperature.« less

Hydrogen retention in lithium and lithium oxide films

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

Buzi, L.; Yang, Y.; Dominguez-Gutierrez, F. J.

Pure lithium (Li) surfaces are difficult to maintain in fusion devices due to rapid oxide formation, therefore, parameterizing and understanding the mechanisms of hydrogen (H, D) retention in lithium oxide (Li 2O) in addition to pure Li is crucial for Li plasma-facing material applications. To compare H retention in Li and Li 2O films, measurements were made as a function of surface temperature (90–520 K) under ultrahigh vacuum (UHV) conditions using temperature programmed desorption (TPD). In both cases, the total retention dropped with surface temperature, from 95% at 90 K to 35% at 520 K Li 2O films retained Hmore » in similar amounts as pure Li. Finally, Molecular Dynamics (MD) modeling was used to elucidate the mechanisms of H retention, and results were consistent with experiments in terms of both retention fraction and the drop of retention with temperature.« less

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

Predictors of Calcium Retention in Adolescent Boys

PubMed Central

Hill, Kathleen M.; Braun, Michelle; Kern, Mark; Martin, Berdine R.; Navalta, James W.; Sedlock, Darlene A.; McCabe, Linda; McCabe, George P.; Peacock, Munro; Weaver, Connie M.

2008-01-01

Context: The relationship between calcium (Ca) intake and Ca retention in adolescent boys was recently reported. Objective: This study evaluated the influence of Ca intake, serum hormone levels, biomarkers of bone metabolism, habitual physical activity, habitual Ca intake, and physical fitness on Ca retention in the same sample. Design: This study was a randomized, cross-over design that consisted of two 3-wk metabolic balance periods. Setting: The study took place on a university campus as a summer camp. Patients or Other Participants: A total of 31 American white boys (13–15 yr) participated in the study. Interventions: Each subject consumed a controlled diet with one of five high-low Ca intake pairs that ranged from 670-2003 mg/d, which was manipulated utilizing a fortified beverage. Main Outcome Measures: Ca retention was determined by Ca intake minus urinary and fecal Ca excretion during each balance period. Results: Ca intake explained 21.7% of the variability in Ca retention, and serum IGF-I concentration explained an additional 11.5%. Other serum hormone levels did not significantly add to the model. Biomarkers of bone metabolism, habitual physical activity, habitual Ca intake, and physical fitness were not significant predictors of Ca retention in adolescent boys. Conclusions: IGF-I, a regulator of growth during puberty, is an important predictor of Ca retention in adolescent boys. However, dietary Ca intake is an even greater predictor of Ca retention during this period of growth. PMID:18840643

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.

Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.

PubMed

Demetriadou, Anthi; Morales-Sanfrutos, Julia; Nearchou, Marianna; Baba, Otto; Kyriacou, Kyriacos; Tate, Edward W; Drousiotou, Anthi; Petrou, Petros P

2017-03-01

Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N -myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria. © 2017. Published by The Company of Biologists Ltd.

Coxsackievirus A16 infection triggers apoptosis in RD cells by inducing ER stress.

PubMed

Zhu, Guoguo; Zheng, Yingcheng; Zhang, Lianglu; Shi, Yingying; Li, Wenhua; Liu, Zhongchun; Peng, Biwen; Yin, Jun; Liu, Wanhong; He, Xiaohua

2013-11-29

Coxsackievirus A16 (CA16) infection, which is responsible for hand, foot and mouth disease (HFMD), has become a common health problem in Asia due to the prevalence of the virus. Thus, it is important to understand the pathogenesis of CA16 infection. Viruses that induce endoplasmic reticulum (ER) stress are confronted with the unfolded protein response (UPR), which may lead to apoptotic cell death and influence viral replication. In this study, we found that CA16 infection could induce apoptosis and ER stress in RD cells. Interestingly, apoptosis via the activation of caspase-3, -8 and -9 in the extrinsic or intrinsic apoptotic pathways in RD cells was inhibited by 4-phenyl butyric acid (4PBA), a chemical chaperone that reduces ER stress. These results suggest that CA16 infection leads to ER stress, which in turn results in prolonged ER stress-induced apoptosis. This study provides a new basis for understanding CA16 infection and host responses. Copyright © 2013 Elsevier Inc. All rights reserved.

Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides.

PubMed

Hinrich, Anthony J; Jodelka, Francine M; Chang, Jennifer L; Brutman, Daniella; Bruno, Angela M; Briggs, Clark A; James, Bryan D; Stutzmann, Grace E; Bennett, David A; Miller, Steven A; Rigo, Frank; Marr, Robert A; Hastings, Michelle L

2016-04-01

Apolipoprotein E receptor 2 (ApoER2) is an apolipoprotein E receptor involved in long-term potentiation, learning, and memory. Given its role in cognition and its association with the Alzheimer's disease (AD) risk gene, apoE, ApoER2 has been proposed to be involved in AD, though a role for the receptor in the disease is not clear. ApoER2 signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that the balance of ApoER2 exon 19 splicing is deregulated in postmortem brain tissue from AD patients and in a transgenic mouse model of AD To test the role of deregulated ApoER2 splicing in AD, we designed an antisense oligonucleotide (ASO) that increases exon 19 splicing. Treatment of AD mice with a single dose of ASO corrected ApoER2 splicing for up to 6 months and improved synaptic function and learning and memory. These results reveal an association between ApoER2 isoform expression and AD, and provide preclinical evidence for the utility of ASOs as a therapeutic approach to mitigate Alzheimer's disease symptoms by improving ApoER2 exon 19 splicing. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Emerging features of ER resident J-proteins in plants

PubMed Central

Ohta, Masaru; Takaiwa, Fumio

2014-01-01

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

5 CFR 293.511 - Retention schedule.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Retention schedule. 293.511 Section 293.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.511 Retention schedule. (a) Temporary EMFS records must...

5 CFR 293.511 - Retention schedule.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Retention schedule. 293.511 Section 293.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.511 Retention schedule. (a) Temporary EMFS records must...

5 CFR 293.511 - Retention schedule.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Retention schedule. 293.511 Section 293.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.511 Retention schedule. (a) Temporary EMFS records must...

5 CFR 293.511 - Retention schedule.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Retention schedule. 293.511 Section 293.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.511 Retention schedule. (a) Temporary EMFS records must...

5 CFR 293.511 - Retention schedule.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Retention schedule. 293.511 Section 293.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.511 Retention schedule. (a) Temporary EMFS records must...

A strategic approach to employee retention.

PubMed

Gering, John; Conner, John

2002-11-01

A sound retention strategy should incorporate a business plan, a value proposition, progress measures, and management influences. The business plan will indicate whether a healthcare organization will achieve a return on investment for its effort. A value proposition will showcase an organization's strengths and differentiate it from its competitors. Measuring progress toward meeting retention goals at regular intervals will help keep an organization on track. The best managers require accountability, rewarding employees for their successes and taking corrective action as necessary. Retention rate targets must be at a level that will achieve a competitive advantage in the served market.

Liposome retention in size exclusion chromatography

PubMed Central

Ruysschaert, Tristan; Marque, Audrey; Duteyrat, Jean-Luc; Lesieur, Sylviane; Winterhalter, Mathias; Fournier, Didier

2005-01-01

Background Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void. Results Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase. Conclusion Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography. PMID:15885140

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.

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.

7 CFR 3015.21 - Retention period.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Retention period. 3015.21 Section 3015.21 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Record Retention and Access Requirements § 3015.21...

Emotional Intelligence and Nursing Student Retention

ERIC Educational Resources Information Center

Wilson, Victoria Jane

2013-01-01

The study examined the constructs of a Multi-Intelligence Model of Retention with four constructs: cognitive and emotional-social intelligence, student characteristics, and environmental factors. Data were obtained from sophomore students entering two diploma, nine associate, and five baccalaureate nursing programs. One year later, retention and…

12 CFR 609.945 - Records retention.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Records retention. 609.945 Section 609.945 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ELECTRONIC COMMERCE Standards for Boards and Management § 609.945 Records retention. Records stored electronically must be accurate, accessible...

5 CFR 351.404 - Retention register.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Retention register. 351.404 Section 351.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.404 Retention register. (a) When a competing employee is to be released...

5 CFR 351.404 - Retention register.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Retention register. 351.404 Section 351.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.404 Retention register. (a) When a competing employee is to be released...

5 CFR 351.404 - Retention register.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Retention register. 351.404 Section 351.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.404 Retention register. (a) When a competing employee is to be released...

5 CFR 351.404 - Retention register.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Retention register. 351.404 Section 351.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.404 Retention register. (a) When a competing employee is to be released...

5 CFR 351.404 - Retention register.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Retention register. 351.404 Section 351.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.404 Retention register. (a) When a competing employee is to be released...

African Retentions in Blues and Jazz.

ERIC Educational Resources Information Center

Meadows, Eddie S.

1979-01-01

The perseverance of African musical characteristics among American Blacks is an historic reality. African retentions have been recorded in Black music of the antebellum period. Various African scales and rhythms permeate Black American music today as evidenced in the retentions found in blues and jazz. (RLV)

12 CFR 609.945 - Records retention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Records retention. 609.945 Section 609.945 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ELECTRONIC COMMERCE Standards for Boards and Management § 609.945 Records retention. Records stored electronically must be accurate, accessible...

[Preparation and photoluminescence study of Er3+ : Y2O3 transparent ceramics].

PubMed

Luo, Jun-ming; Li, Yong-xiu; Deng, Li-ping

2008-10-01

Y2O3 acted as the matrix material, which was doped with different concentrations of Er3+, Er3+ : Y2O3 nanocrystalline powder was prepared by co-precipitation method, and Er3+ : Y2O3 transparent ceramics was fabricated by vacuum sintering at 1700 degrees C, 1 x 10(-3) Pa for 8 h. By using the X-ray diffraction (D/MAX-RB), transmission electron microscopy(Philips EM420), automatic logging spectrophotometer(DMR-22), fluorescence analyzer (F-4500) and 980 nm diode laser, the structural, morphological and luminescence properties of the sample were investigated. The results show that Er3+ dissolved completely in the Y2O3 cubic phase, the precursor was amorphous, weak diffraction peaks appeared after calcination at 400 degrees C, and if calcined at 700 degrees C, the precursor turned to pure cubic phase. With increasing the calcining temperature, the diffraction peaks became sharp quickly, and when the calcining temperature reached 1100 degrees C, the diffraction peaks became very sharp, indicating that the grains were very large. The particles of Er+ : Y2O3 is homogeneous and nearly spherical, the average diameter of the particles is in the range of 40-60 nm after being calcined at 1000 degrees C for 2 h. The relative density of Er3+ : Y2O3 transparent ceramics is 99.8%, the transmittance of the Er2+ : Y2O3 transparent ceramics is markedly lower than the single crystal at the short wavelength, but the transmittance is improved noticeably with increasing the wavelength, and the transmittance exceeds 60% at the wavelength of 1200 nm. Excited under the 980 nm diode laser, there are two main up-conversion emission bands, green emission centers at 562 nm and red emission centers at 660 nm, which correspond to (4)S(3/2) / (2)H(11/2) - (4)I(15/2) and (4)F(9/2) - (4)I(15/2) radiative transitions respectively. By changing the doping concentrations of Er3+, the color of up-conversion luminescence can be tuned from green to red gradually. The luminescence intensity is not reinforce