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Sample records for proximal nhe3 promoter

  1. Dopamine D3 receptor inhibits the ubiquitin-specific peptidase 48 to promote NHE3 degradation

    PubMed Central

    Armando, Ines; Villar, Van Anthony M.; Jones, John E.; Lee, Hewang; Wang, Xiaoyan; Asico, Laureano D.; Yu, Peiying; Yang, Jian; Escano, Crisanto S.; Pascua-Crusan, Annabelle M.; Felder, Robin A.; Jose, Pedro A.

    2014-01-01

    The dopamine D3 receptor (D3R) is crucial in the regulation of blood pressure and sodium balance, in that Drd3 gene ablation in mice results in hypertension and failure to excrete a dietary salt load. The mechanism responsible for the renal sodium retention in these mice is largely unknown. We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin-specific peptidase 48 (USP48), thereby promoting Na+-H+ exchanger (NHE)-3 degradation. We found that stimulation with the D3R-specific agonist PD128907 (1 μM, 30 min) promoted the interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (−35±6%, vs. vehicle), resulting in increased ubiquitinylated NHE3 (+140±10%); and decreased NHE3 expression (−50±9%) in human renal proximal tubule cells (hRPTCs). USP48 silencing decreased NHE3's half-life (USP48 siRNA t1/2=6.1 h vs. vehicle t1/2=12.9 h), whereas overexpression of USP48 increased NHE3 half-life (t1/2=21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation. USP48 accounted for ∼30% of the total deubiquitinylating activity in these cells. Extending our studies in vivo, we found that pharmacologic blockade of D3R via the D3R-specific antagonist GR103691 (1 μg/kg/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310±15%, vs. vehicle), whereas an innovative kidney-restricted Usp48 silencing via siRNA (3 μg/d, 7 d) increased ubiquitinylated NHE3 (+250±30%, vs. controls), decreased total NHE3 (−23±2%), and lowered blood pressure (−24±2 mm Hg), compared with that in control mice that received either the vehicle or nonsilencing siRNA. Our data demonstrate a crucial role for the dynamic interaction between D3R and USP48 in the regulation of NHE3 expression and function.—Armando, I., Villar, V. A. M., Jones J. E., Lee, H., Wang, X., Asico L. D., Yu, P., Yang, J., Escano, C. S. Jr., Pascua

  2. Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells.

    PubMed

    Solocinski, Kristen; Richards, Jacob; All, Sean; Cheng, Kit-Yan; Khundmiri, Syed J; Gumz, Michelle L

    2015-12-01

    We have previously demonstrated that the circadian clock protein period (Per)1 coordinately regulates multiple genes involved in Na(+) reabsorption in renal collecting duct cells. Consistent with these results, Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice. The proximal tubule is responsible for a majority of Na(+) reabsorption. Previous work has demonstrated that expression of Na(+)/H(+) exchanger 3 (NHE3) oscillates with a circadian pattern and Na(+)-glucose cotransporter (SGLT)1 has been demonstrated to be a circadian target in the colon, but whether these target genes are regulated by Per1 has not been investigated in the kidney. The goal of the present study was to determine if Per1 regulates the expression of NHE3, SGLT1, and SGLT2 in the kidney. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of SGLT1 and NHE3 but not SGLT2 in the renal cortex of mice. Per1 small interfering RNA and pharmacological blockade of Per1 nuclear entry in human proximal tubule HK-2 cells yielded the same results. Examination of heterogeneous nuclear RNA suggested that the effects of Per1 on NHE3 and SGLT1 expression occurred at the level of transcription. Per1 and the circadian protein CLOCK were detected at promoters of NHE3 and SGLT1. Importantly, both membrane and intracellular protein levels of NHE3 and SGLT1 were decreased after blockade of nuclear Per1 entry. This effect was associated with reduced activity of Na(+)-K(+)-ATPase. These data demonstrate a role for Per1 in the transcriptional regulation of NHE3 and SGLT1 in the kidney. PMID:26377793

  3. Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling.

    PubMed

    Carneiro de Morais, Carla P; Polidoro, Juliano Z; Ralph, Donna L; Pessoa, Thaissa D; Oliveira-Souza, Maria; Barauna, Valério G; Rebouças, Nancy A; Malnic, Gerhard; McDonough, Alicia A; Girardi, Adriana C C

    2015-10-15

    Physiological concentrations of angiotensin II (ANG II) upregulate the activity of Na(+)/H(+) exchanger isoform 3 (NHE3) in the renal proximal tubule through activation of the ANG II type I (AT1) receptor/G protein-coupled signaling. This effect is key for maintenance of extracellular fluid volume homeostasis and blood pressure. Recent findings have shown that selective activation of the beta-arrestin-biased AT1 receptor signaling pathway induces diuresis and natriuresis independent of G protein-mediated signaling. This study tested the hypothesis that activation of this AT1 receptor/beta-arrestin signaling inhibits NHE3 activity in proximal tubule. To this end, we determined the effects of the compound TRV120023, which binds to the AT1R, blocks G-protein coupling, and stimulates beta-arrestin signaling on NHE3 function in vivo and in vitro. NHE3 activity was measured in both native proximal tubules, by stationary microperfusion, and in opossum proximal tubule (OKP) cells, by Na(+)-dependent intracellular pH recovery. We found that 10(-7) M TRV120023 remarkably inhibited proximal tubule NHE3 activity both in vivo and in vitro. Additionally, stimulation of NHE3 by ANG II was completely suppressed by TRV120023 both in vivo as well as in vitro. Inhibition of NHE3 activity by TRV120023 was associated with a decrease in NHE3 surface expression in OKP cells and with a redistribution from the body to the base of the microvilli in the rat proximal tubule. These findings indicate that biased signaling of the beta-arrestin pathway through the AT1 receptor inhibits NHE3 activity in the proximal tubule at least in part due to changes in NHE3 subcellular localization. PMID:26246427

  4. Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis

    PubMed Central

    Laghmani, Kamel; Preisig, Patricia A.; Moe, Orson W.; Yanagisawa, Masashi; Alpern, Robert J.

    2001-01-01

    Decreases in blood pH activate NHE3, the proximal tubular apical membrane Na/H antiporter. In cultured renal epithelial cells, activation of the endothelin-B (ETB) receptor increases NHE3 activity. To examine the role of the ETB receptor in the response to acidosis in vivo, the present studies examined ETB receptor–deficient mice, rescued from neonatal lethality by expression of a dopamine β-hydroxylase promoter/ETB receptor transgene (Tg/Tg:ETB–/– mice). In proximal tubule suspensions from Tg/Tg:ETB+/– mice, 10–8 M endothelin-1 (ET-1) increased NHE3 activity, but this treatment had no effect on tubules from Tg/Tg:ETB–/– mice. Acid ingestion for 7 days caused a greater decrease in blood HCO3– concentration in Tg/Tg:ETB–/– mice compared with Tg/Tg:ETB+/+ and Tg/Tg:ETB+/– mice. Whereas acid ingestion increased apical membrane NHE3 by 42–46% in Tg/Tg:ETB+/+ and Tg/Tg:ETB+/– mice, it had no effect on NHE3 in Tg/Tg:ETB–/– mice. In C57BL/6 mice, excess acid ingestion increased renal cortical preproET-1 mRNA expression 2.4-fold and decreased preproET-3 mRNA expression by 37%. On a control diet, Tg/Tg:ETB–/– mice had low rates of ammonium excretion, which could not be attributed to an inability to acidify the urine, as well as hypercitraturia, with increased titratable acid excretion. Acid ingestion increased ammonium excretion, citrate absorption, and titratable acid excretion to the same levels in Tg/Tg:ETB–/– and Tg/Tg:ETB+/+ mice. In conclusion, metabolic acidosis increases ET-1 expression, which increases NHE3 activity via the ETB receptor. PMID:11413164

  5. Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3.

    PubMed

    Krishnan, Devishree; Liu, Lei; Wiebe, Shane A; Casey, Joseph R; Cordat, Emmanuelle; Alexander, R Todd

    2015-08-15

    Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay. Direct physical interaction was confirmed in solid-phase binding assays with immobilized CAII and C-terminal NHE3 glutathione-S-transferase fusion constructs. To assess the effect of CAII on NHE3 function, we expressed NHE3 in a proximal tubule cell line and measured NHE3 activity as the rate of intracellular pH recovery, following an acid load. NHE3-expressing cells had a significantly greater rate of intracellular pH recovery than controls. Inhibition of endogenous CAII activity with acetazolamide significantly decreased NHE3 activity, indicating that CAII activates NHE3. To ascertain whether CAII binding per se activates NHE3, we expressed NHE3 with wild-type CAII, a catalytically inactive CAII mutant (CAII-V143Y), or a mutant unable to bind other transporters (CAII-HEX). NHE3 activity increased upon wild-type CAII coexpression, but not in the presence of the CAII V143Y or HEX mutant. Together these studies support an association between CAII and NHE3 that alters the transporter's activity. PMID:26041446

  6. Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3

    PubMed Central

    Krishnan, Devishree; Liu, Lei; Wiebe, Shane A.; Casey, Joseph R.; Cordat, Emmanuelle; Alexander, R. Todd

    2016-01-01

    Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay. Direct physical interaction was confirmed in solid-phase binding assays with immobilized CAII and C-terminal NHE3 glutathione-S-transferase fusion constructs. To assess the effect of CAII on NHE3 function, we expressed NHE3 in a proximal tubule cell line and measured NHE3 activity as the rate of intracellular pH recovery, following an acid load. NHE3-expressing cells had a significantly greater rate of intracellular pH recovery than controls. Inhibition of endogenous CAII activity with acetazolamide significantly decreased NHE3 activity, indicating that CAII activates NHE3. To ascertain whether CAII binding per se activates NHE3, we expressed NHE3 with wild-type CAII, a catalytically inactive CAII mutant (CAII-V143Y), or a mutant unable to bind other transporters (CAII-HEX). NHE3 activity increased upon wild-type CAII coexpression, but not in the presence of the CAII V143Y or HEX mutant. Together these studies support an association between CAII and NHE3 that alters the transporter’s activity. PMID:26041446

  7. Lactobacillus acidophilus upregulates intestinal NHE3 expression and function

    PubMed Central

    Singh, Varsha; Raheja, Geetu; Borthakur, Alip; Kumar, Anoop; Gill, Ravinder K.; Alakkam, Anas; Malakooti, Jaleh

    2012-01-01

    A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl−/HCO3− exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl−/HCO3− exchange activity via an increase in the surface levels and expression of the Cl−/HCO3− exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8–24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics. PMID:23086913

  8. Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity

    PubMed Central

    Zhu, Xinjun Cindy; Sarker, Rafiquel; Horton, John R.; Chakraborty, Molee; Chen, Tian-E; Tse, C. Ming; Cha, Boyoung

    2015-01-01

    Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function. PMID:25715704

  9. Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine

    PubMed Central

    Jakab, Robert L.; Collaco, Anne M.

    2011-01-01

    We examined the cell-specific subcellular expression patterns for sodium- and potassium-coupled chloride (NaK2Cl) cotransporter 1 (NKCC1), Na+ bicarbonate cotransporter (NBCe1), cystic fibrosis transmembrane conductance regulator (CFTR), and Na+/H+ exchanger 3 (NHE3) to understand the functional plasticity and synchronization of ion transport functions along the crypt-villus axis and its relevance to intestinal disease. In the unstimulated intestine, all small intestinal villus enterocytes coexpressed apical CFTR and NHE3, basolateral NBCe1, and mostly intracellular NKCC1. All (crypt and villus) goblet cells strongly expressed basolateral NKCC1 (at approximately three-fold higher levels than villus enterocytes), but no CFTR, NBCe1, or NHE3. Lower crypt cells coexpressed apical CFTR and basolateral NKCC1, but no NHE3 or NBCe1 (except NBCe1-expressing proximal colonic crypts). CFTR, NBCe1, and NKCC1 colocalized with markers of early and recycling endosomes, implicating endocytic recycling in cell-specific anion transport. Brunner's glands of the proximal duodenum coexpressed high levels of apical/subapical CFTR and basolateral NKCC1, but very low levels of NBCe1, consistent with secretion of Cl−-enriched fluid into the crypt. The cholinergic agonist carbachol rapidly (within 10 min) reduced cell volume along the entire crypt/villus axis and promoted NHE3 internalization into early endosomes. In contrast, carbachol induced membrane recruitment of NKCC1 and CFTR in all crypt and villus enterocytes, NKCC1 in all goblet cells, and NBCe1 in all villus enterocytes. These observations support regulated vesicle traffic in Cl− secretion by goblet cells and Cl− and HCO3− secretion by villus enterocytes during the transient phase of cholinergic stimulation. Overall, the carbachol-induced membrane trafficking profile of the four ion transporters supports functional plasticity of the small intestinal villus epithelium that enables it to conduct both absorptive and

  10. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3

    PubMed Central

    Fenton, Robert A.; Poulsen, Søren B.; de la Mora Chavez, Samantha; Soleimani, Manoocher; Busslinger, Meinrad; Rieg, Timo

    2015-01-01

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation, resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2, and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605, or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na+/bicarbonate cotransporter NBCe1, pretreatment with DIDS inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis. PMID:25925253

  11. Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells

    SciTech Connect

    Amin, Md Ruhul; Ghannad, Leda; Othman, Ahmad; Gill, Ravinder K.; Dudeja, Pradeep K.; Ramaswamy, Krishnamurthy; Malakooti, Jaleh

    2009-05-08

    Serotonin (5-HT) decreases NHE2 and NHE3 activities under acute conditions in human intestinal epithelial cells. Here, we have investigated the effects of 5-HT on expression of the human NHE3 gene and the mechanisms underlying its transcriptional regulation in differentiated C2BBe1 cells. Treatment of the human intestinal epithelial cell line, C2BBe1, with 5-HT (20 {mu}M) resulted in a significant decrease in NHE3 mRNA and protein expression. In transient transfection studies, 5-HT repressed the NHE3 promoter activity by {approx}55%. The repression of the NHE3 promoter activity in response to 5-HT was accompanied by reduced DNA-binding activity of transcription factors Sp1 and Sp3 to the NHE3 promoter without alteration in their nuclear levels. Pharmacological inhibitors of protein kinase C reversed the inhibitory effect of 5-HT on the promoter activity. Our data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKC{alpha} and modulation of DNA-binding affinities of Sp1 and Sp3.

  12. Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2.

    PubMed

    No, Yi Ran; He, Peijian; Yoo, Byong Kwon; Yun, C Chris

    2015-07-01

    Na(+)/H(+) exchange by Na(+)/H(+) exchanger 3 (NHE3) is a major route of sodium absorption in the intestine and kidney. We have shown previously that lysophosphatidic acid (LPA), a small phospholipid produced ubiquitously by all types of cells, stimulates NHE3 via LPA5 receptor. Stimulation of NHE3 activity by LPA involves LPA5 transactivating EGF receptor (EGFR) in the apical membrane. EGFR activates proline-rich tyrosine kinase 2 (Pyk2) and ERK, both of which are necessary for NHE3 regulation. However, Pyk2 and ERK are regulated by EGFR via independent pathways and appear to converge on an unidentified intermediate that ultimately targets NHE3. The p90 ribosomal S6 kinase (RSK) family of Ser/Thr protein kinases is a known effector of EGFR and ERK. Hence, we hypothesized that RSK may be the convergent effector of Pyk2 and ERK although it is not known whether Pyk2 regulates RSK. In this study, we show that Pyk2 is necessary for the maintenance of phosphoinositide-dependent kinase 1 (PDK1) autophosphorylation, and knockdown of Pyk2 or PDK1 mitigated LPA-induced phosphorylation of RSK and stimulation of NHE3 activity. Additionally, we show that RSK2, but not RSK1, is responsible for NHE3 regulation. RSK2 interacts with NHE3 at the apical membrane domain, where it phosphorylates NHE3. Alteration of S663 of NHE3 ablated LPA-induced phosphorylation of NHE3 and stimulation of the transport activity. Our study identifies RSK2 as a new kinase that regulates NHE3 activity by direct phosphorylation. PMID:25855080

  13. Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2

    PubMed Central

    No, Yi Ran; He, Peijian; Yoo, Byong Kwon

    2015-01-01

    Na+/H+ exchange by Na+/H+ exchanger 3 (NHE3) is a major route of sodium absorption in the intestine and kidney. We have shown previously that lysophosphatidic acid (LPA), a small phospholipid produced ubiquitously by all types of cells, stimulates NHE3 via LPA5 receptor. Stimulation of NHE3 activity by LPA involves LPA5 transactivating EGF receptor (EGFR) in the apical membrane. EGFR activates proline-rich tyrosine kinase 2 (Pyk2) and ERK, both of which are necessary for NHE3 regulation. However, Pyk2 and ERK are regulated by EGFR via independent pathways and appear to converge on an unidentified intermediate that ultimately targets NHE3. The p90 ribosomal S6 kinase (RSK) family of Ser/Thr protein kinases is a known effector of EGFR and ERK. Hence, we hypothesized that RSK may be the convergent effector of Pyk2 and ERK although it is not known whether Pyk2 regulates RSK. In this study, we show that Pyk2 is necessary for the maintenance of phosphoinositide-dependent kinase 1 (PDK1) autophosphorylation, and knockdown of Pyk2 or PDK1 mitigated LPA-induced phosphorylation of RSK and stimulation of NHE3 activity. Additionally, we show that RSK2, but not RSK1, is responsible for NHE3 regulation. RSK2 interacts with NHE3 at the apical membrane domain, where it phosphorylates NHE3. Alteration of S663 of NHE3 ablated LPA-induced phosphorylation of NHE3 and stimulation of the transport activity. Our study identifies RSK2 as a new kinase that regulates NHE3 activity by direct phosphorylation. PMID:25855080

  14. Casein Kinase 2 Binds to the C Terminus of Na+/H+ exchanger 3 (NHE3) and Stimulates NHE3 Basal Activity by Phosphorylating a Separate Site in NHE3

    PubMed Central

    Sarker, Rafiquel; Grønborg, Mads; Cha, Boyoung; Mohan, Sachin; Chen, Yueping; Pandey, Akhilesh; Litchfield, David

    2008-01-01

    Na+/H+ exchanger 3 (NHE3) is the epithelial-brush border isoform responsible for most intestinal and renal Na+ absorption. Its activity is both up- and down-regulated under normal physiological conditions, and it is inhibited in most diarrheal diseases. NHE3 is phosphorylated under basal conditions and Ser/Thr phosphatase inhibitors stimulate basal exchange activity; however, the kinases involved are unknown. To identify kinases that regulate NHE3 under basal conditions, NHE3 was immunoprecipitated; LC-MS/MS of trypsinized NHE3 identified a novel phosphorylation site at S719 of the C terminus, which was predicted to be a casein kinase 2 (CK2) phosphorylation site. This was confirmed by an in vitro kinase assay. The NHE3-S719A mutant but not NHE3-S719D had reduced NHE3 activity due to less plasma membrane NHE3. This was due to reduced exocytosis plus decreased plasma membrane delivery of newly synthesized NHE3. Also, NHE3 activity was inhibited by the CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole DMAT when wild-type NHE3 was expressed in fibroblasts and Caco-2 cells, but the NHE3-S719 mutant was fully resistant to DMAT. CK2 bound to the NHE3 C-terminal domain, between amino acids 590 and 667, a site different from the site it phosphorylates. CK2 binds to the NHE3 C terminus and stimulates basal NHE3 activity by phosphorylating a separate single site on the NHE3 C terminus (S719), which affects NHE3 trafficking. PMID:18614797

  15. NHE3 function and phosphorylation are regulated by a calyculin A-sensitive phosphatase

    PubMed Central

    Dynia, Diane W.; Steinmetz, Amy G.

    2010-01-01

    Na+/H+ exchanger 3 (NHE3) is phosphorylated and regulated by multiple kinases, including PKA, SGK1, and CK2; however, the role of phosphatases in the dephosphorylation and regulation of NHE3 remains unknown. The purpose of this study was to determine whether serine/threonine phosphatases alter NHE3 activity and phosphorylation and, if so, at which sites. To this end, we first examined the effects of calyculin A [a combined protein phosphatase 1 (PP1) and PP2A inhibitor] and okadaic acid (a PP2A inhibitor) on general and site-specific NHE3 phosphorylation. Calyculin A induced a phosphorylation-dependent NHE3 gel mobility shift and increased NHE3 phosphorylation at serines 552 and 605. No change in NHE3 phosphorylation was detected after okadaic acid treatment. An NHE3 gel mobility shift was also evident in calyculin A-treated COS-7 cells transfected with either wild-type or mutant (S552A, S605G, S661A, S716A) rat NHE3. Since the NHE3 gel mobility shift occurred despite mutation of known phosphorylation sites, novel sites of phosphorylation must also exist. Next, we assayed NHE3 activity in response to calyculin A and okadaic acid and found that calyculin A induced a 24% inhibition of NHE3 activity, whereas okadaic acid had no effect. When all known NHE3 phosphorylation sites were mutated, calyculin A induced a stimulation of NHE3 activity, demonstrating a functional significance for the novel phosphorylation sites. Finally, we established that the PP1 catalytic subunit can directly dephosphorylate immunopurified NHE3 in vitro. In conclusion, our data demonstrate that a calyculin A-sensitive phosphatase, most likely PP1, is involved in the regulation and dephosphorylation of NHE3 at known and novel sites. PMID:20015946

  16. Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss

    PubMed Central

    He, Peijian; Zhao, Luqing; Zhu, Lixin; Weinman, Edward J.; De Giorgio, Roberto; Koval, Michael; Srinivasan, Shanthi; Yun, C. Chris

    2015-01-01

    Diarrhea is one of the troublesome complications of diabetes, and the underlying causes of this problem are complex. Here, we investigated whether altered electrolyte transport contributes to diabetic diarrhea. We found that the expression of Na+/H+ exchanger NHE3 and several scaffold proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate (IP3) receptor-binding protein released with IP3 (IRBIT), and ezrin, was decreased in the intestinal brush border membrane (BBM) of mice with streptozotocin-induced diabetes. Treatment of diabetic mice with insulin restored intestinal NHE3 activity and fluid absorption. Molecular analysis revealed that NHE3, NHERF1, IRBIT, and ezrin form macrocomplexes, which are perturbed under diabetic conditions, and insulin administration reconstituted these macrocomplexes and restored NHE3 expression in the BBM. Silencing of NHERF1 or IRBIT prevented NHE3 trafficking to the BBM and insulin-dependent NHE3 activation. IRBIT facilitated the interaction of NHE3 with NHERF1 via protein kinase D2–dependent phosphorylation. Insulin stimulated ezrin phosphorylation, which enhanced the interaction of ezrin with NHERF1, IRBIT, and NHE3. Additionally, oral administration of lysophosphatidic acid (LPA) increased NHE3 activity and fluid absorption in diabetic mice via an insulin-independent pathway. Together, these findings indicate the importance of NHE3 in diabetic diarrhea and suggest LPA administration as a potential therapeutic strategy for management of diabetic diarrhea. PMID:26258413

  17. Functional dissection of the lck proximal promoter.

    PubMed Central

    Allen, J M; Forbush, K A; Perlmutter, R M

    1992-01-01

    The lck gene encodes a protein tyrosine kinase that participates in lymphocyte-specific signal transduction pathways. Previous studies have established that lck transcription is regulated by two distinct promoter elements termed proximal (or 3') and distal (or 5'). The proximal promoter is active almost exclusively in thymocytes and becomes inactive later during T-cell maturation. To dissect the mechanisms responsible for lck gene regulation, we generated transgenic animals bearing 5' truncations in the proximal promoter element. Sequences between -584 and +37 with respect to the proximal promoter transcription start site act to direct tissue-specific and temporally correct transcription of either a tagged version of the lck gene itself or a heterologous reporter sequence (lacZ). This region contains binding sites for at least five distinct nuclear proteins, of which one is found only in cells that support proximal lck promoter activity and a second appears only in nonexpressing cells. Interestingly, the transcribed region of the lck gene contains positive control elements that can substantially boost expression from minimal (-130 bp) proximal promoter constructs. These results provide a basis for the biochemical dissection of transcriptional regulators that act at defined points during T-cell development. Images PMID:1588967

  18. Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension in NHE3-deficient mice with transgenic rescue of NHE3 in small intestines

    PubMed Central

    Li, Xiao C; Shull, Gary E; Miguel-Qin, Elisa; Chen, Fang; Zhuo, Jia L

    2015-01-01

    The role of Na+/H+ exchanger 3 (NHE3) in the kidney in angiotensin II (ANG II)-induced hypertension remains unknown. The present study used global NHE3-deficient mice with transgenic rescue of the Nhe3 gene in small intestines (tgNhe3−/−) to test the hypothesis that genetic deletion of NHE3 selectively in the kidney attenuates ANG II-induced hypertension. Six groups of wild-type (tgNhe3+/+) and tgNhe3−/− mice were infused with either vehicle or ANG II (1.5 mg/kg/day, i.p., 2 weeks, or 10 nmol/min, i.v., 30 min), treated with or without losartan (20 mg/kg/day, p.o.) for 2 weeks. Basal systolic blood pressure (SBP) and mean intra-arterial blood pressure (MAP) were significantly lower in tgNhe3−/− mice (P < 0.01). Basal glomerular filtration rate, 24 h urine excretion, urinary Na+ excretion, urinary K+ excretion, and urinary Cl− excretion were significantly lower in tgNhe3−/− mice (P < 0.01). These responses were associated with significantly elevated plasma ANG II and aldosterone levels, and marked upregulation in aquaporin 1, the Na+/HCO3 cotransporter, the α1 subunit isoform of Na+/K+-ATPase, protein kinase Cα, MAP kinases ERK1/2, and glycogen synthase kinase 3 α/β in the renal cortex of tgNhe3−/− mice (P < 0.01). ANG II infusion markedly increased SBP and MAP and renal cortical transporter and signaling proteins in tgNhe3+/+, as expected, but all of these responses to ANG II were attenuated in tgNhe3−/− mice (P < 0.01). These results suggest that NHE3 in the kidney is necessary for maintaining normal blood pressure and fully developing ANG II-dependent hypertension. PMID:26564064

  19. Promoting proximal formative assessment with relational discourse

    NASA Astrophysics Data System (ADS)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.

    2012-02-01

    The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

  20. NHE3 phosphorylation via PKCη marks the polarity and orientation of directionally migrating cells

    PubMed Central

    Bola, Sharanya; Zhang, Lei; Reid, Brian; Fu, Guo; Funk, Richard H. W.; Zhao, Min

    2015-01-01

    Endogenous electric fields (EF) may provide an overriding cue for directional cell migration during wound closure. Perceiving a constant direction requires active sodium-hydrogen exchanger (pNHE3) at the leading edge of HEK 293 cells but its activation mechanism is not yet fully understood. Because protein kinase C (PKC) is required in electrotaxis, we asked whether NHE3 is activated by PKC during wound healing. Using pharmacological (pseudosubstrate and edelfosine) inhibition, we showed that inhibition of PKCη isoform impairs directional cell migration in HEK 293 cells in the presence of a persistent directional cue (0.25–0.3 V/mm of EF for 2 h). Further, we found that pNHE3 forms complexes with both PKCη and ɣ-tubulin, suggesting that these molecules may regulate the microtubule-organizing center. In addition, cellular pNHE3 content was reduced significantly when PKCη was inhibited during directional cell migration. Taken together, these data suggest that PKCη-dependent phosphorylation of NHE3 and the formation of pNHE3/PKCη/ɣ-tubulin complexes at the leading edge of the cell are required for directional cell migration in an EF. PMID:24788043

  1. Loss of NHE3 alters gut microbiota composition and influences Bacteroides thetaiotaomicron growth

    PubMed Central

    Engevik, Melinda A.; Aihara, Eitaro; Montrose, Marshall H.; Shull, Gary E.; Hassett, Daniel J.

    2013-01-01

    Changes in the intestinal microbiota have been linked to diabetes, obesity, inflammatory bowel disease, and Clostridium difficile (C. difficile)-associated disease. Despite this, it remains unclear how the intestinal environment, set by ion transport, affects luminal and mucosa-associated bacterial composition. Na+/H+-exchanger isoform 3 (NHE3), a target of C. difficile toxin B, plays an integral role in intestinal Na+ absorption. Thus the NHE3-deficient mouse model was chosen to examine the effect of pH and ion composition on bacterial growth. We hypothesized that ion transport-induced change in the intestinal environment would lead to alteration of the microbiota. Region-specific changes in ion composition and pH correlated with region-specific alteration of luminal and mucosal-associated bacteria with general decreases in Firmicutes and increases in Bacteroidetes members. Bacteroides thetaiotaomicron (B. thetaiotaomicron) increased in NHE3−/− terminal ileum and was examined in vitro to determine whether altered Na+ was sufficient to affect growth. Increased in vitro growth of B. thetaiotaomicron occurred in 43 mM Na+ correlating with the NHE3−/− mouse terminal ileum [Na+]. NHE3−/− terminal ileum displayed increased fut2 mRNA and fucosylation correlating with B. thetaiotaomicron growth. Inoculation of B. thetaiotaomicron in wild-type and NHE3−/− terminal ileum organoids displayed increased fut2 and fucosylation, indicating that B. thetaiotaomicron alone is sufficient for the increased fucosylation seen in vivo. These data demonstrate that loss of NHE3 alters the intestinal environment, leading to region-specific changes in bacteria, and shed light on the growth requirements of some gut microbiota members, which is vital for creating better treatments of complex diseases with an altered gut microbiota. PMID:24072680

  2. Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea.

    PubMed

    Janecke, Andreas R; Heinz-Erian, Peter; Yin, Jianyi; Petersen, Britt-Sabina; Franke, Andre; Lechner, Silvia; Fuchs, Irene; Melancon, Serge; Uhlig, Holm H; Travis, Simon; Marinier, Evelyne; Perisic, Vojislav; Ristic, Nina; Gerner, Patrick; Booth, Ian W; Wedenoja, Satu; Baumgartner, Nadja; Vodopiutz, Julia; Frechette-Duval, Marie-Christine; De Lafollie, Jan; Persad, Rabindranath; Warner, Neil; Tse, C Ming; Sud, Karan; Zachos, Nicholas C; Sarker, Rafiquel; Zhu, Xinjun; Muise, Aleixo M; Zimmer, Klaus-Peter; Witt, Heiko; Zoller, Heinz; Donowitz, Mark; Müller, Thomas

    2015-12-01

    Congenital sodium diarrhea (CSD) refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. Syndromic CSD is caused by SPINT2 mutations. While we recently described four cases of the non-syndromic form of CSD that were caused by dominant activating mutations in intestinal receptor guanylate cyclase C (GC-C), the genetic cause for the majority of CSD is still unknown. Therefore, we aimed to determine the genetic cause for non-GC-C non-syndromic CSD in 18 patients from 16 unrelated families applying whole-exome sequencing and/or chromosomal microarray analyses and/or direct Sanger sequencing. SLC9A3 missense, splicing and truncation mutations, including an instance of uniparental disomy, and whole-gene deletion were identified in nine patients from eight families with CSD. Two of these nine patients developed inflammatory bowel disease (IBD) at 4 and 16 years of age. SLC9A3 encodes Na(+)/H(+) antiporter 3 (NHE3), which is the major intestinal brush-border Na(+)/H(+) exchanger. All mutations were in the NHE3 N-terminal transport domain, and all missense mutations were in the putative membrane-spanning domains. Identified SLC9A3 missense mutations were functionally characterized in plasma membrane NHE null fibroblasts. SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal. This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset of patients. PMID:26358773

  3. Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule.

    PubMed

    Pessoa, Thaissa Dantas; Campos, Luciene Cristina Gastalho; Carraro-Lacroix, Luciene; Girardi, Adriana C C; Malnic, Gerhard

    2014-09-01

    Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule. PMID:24652792

  4. A positioned +1 nucleosome enhances promoter-proximal pausing

    PubMed Central

    Jimeno-González, Silvia; Ceballos-Chávez, María; Reyes, José C.

    2015-01-01

    Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleosome is strongly positioned, elongating RNAPII has a tendency to stall at the promoter-proximal region, recruits more negative elongation factor (NELF) and produces less mRNA. The nucleosome-induced pause favors pre-mRNA quality control by promoting the addition of the cap to the nascent RNA. Moreover, the uncapped RNAs produced in the absence of a positioned nucleosome are degraded by the 5′-3′ exonuclease XRN2. Interestingly, reducing the levels of the chromatin remodeler ISWI factor SNF2H decreases +1 nucleosome positioning and increases RNAPII pause release. This work demonstrates a function for +1 nucleosome in regulation of transcription elongation, pre-mRNA processing and gene expression. PMID:25735750

  5. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo

    PubMed Central

    Clayburgh, Daniel R.; Musch, Mark W.; Leitges, Michael; Fu, Yang-Xin; Turner, Jerrold R.

    2006-01-01

    Acute T cell–mediated diarrhea is associated with increased mucosal expression of proinflammatory cytokines, including the TNF superfamily members TNF and LIGHT. While we have previously shown that epithelial barrier dysfunction induced by myosin light chain kinase (MLCK) is required for the development of diarrhea, MLCK inhibition does not completely restore water absorption. In contrast, although TNF-neutralizing antibodies completely restore water absorption after systemic T cell activation, barrier function is only partially corrected. This suggests that, while barrier dysfunction is critical, other processes must be involved in T cell–mediated diarrhea. To define these processes in vivo, we asked whether individual cytokines might regulate different events in T cell–mediated diarrhea. Both TNF and LIGHT caused MLCK-dependent barrier dysfunction. However, while TNF caused diarrhea, LIGHT enhanced intestinal water absorption. Moreover, TNF, but not LIGHT, inhibited Na+ absorption due to TNF-induced internalization of the brush border Na+/H+ exchanger NHE3. LIGHT did not cause NHE3 internalization. PKCα activation by TNF was responsible for NHE3 internalization, and pharmacological or genetic PKCα inhibition prevented NHE3 internalization, Na+ malabsorption, and diarrhea despite continued barrier dysfunction. These data demonstrate the necessity of coordinated Na+ malabsorption and barrier dysfunction in TNF-induced diarrhea and provide insight into mechanisms of intestinal water transport. PMID:17016558

  6. Transcription Factor Binding Site Positioning in Yeast: Proximal Promoter Motifs Characterize TATA-Less Promoters

    PubMed Central

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of ‘proximal promoter motifs’ (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters. PMID:21931670

  7. Squalamine, a novel cationic steroid, specifically inhibits the brush-border Na+/H+ exchanger isoform NHE3.

    PubMed

    Akhter, S; Nath, S K; Tse, C M; Williams, J; Zasloff, M; Donowitz, M

    1999-01-01

    Squalamine, an endogenous molecule found in the liver and other tissues of Squalus acanthias, has antibiotic properties and causes changes in endothelial cell shape. The latter suggested that its potential targets might include transport proteins that control cell volume or cell shape. The effect of purified squalamine was examined on cloned Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 stably transfected in PS120 fibroblasts. Squalamine (1-h pretreatment) decreased the maximal velocity of rabbit NHE3 in a concentration-dependent manner (13, 47, and 57% inhibition with 3, 5, and 7 micrograms/ml, respectively) and also increased K'[H+]i. Squalamine did not affect rabbit NHE1 or NHE2 function. The inhibitory effect of squalamine was 1) time dependent, with no effect of immediate addition and maximum effect with 1 h of exposure, and 2) fully reversible. Squalamine pretreatment of the ileum for 60 min inhibited brush-border membrane vesicle Na+/H+ activity by 51%. Further investigation into the mechanism of squalamine's effects showed that squalamine required the COOH-terminal 76 amino acids of NHE3. Squalamine had no cytotoxic effect at the concentrations studied, as indicated by monitoring lactate dehydrogenase release. These results indicate that squalamine 1) is a specific inhibitor of the brush-border NHE isoform NHE3 and not NHE1 or NHE2, 2) acts in a nontoxic and fully reversible manner, and 3) has a delayed effect, indicating that it may influence brush-border Na+/H+ exchanger function indirectly, through an intracellular signaling pathway or by acting as an intracellular modulator. PMID:9886929

  8. Proximal tubular NHEs: sodium, protons and calcium?

    PubMed Central

    Alexander, R. Todd; Dimke, Henrik; Cordat, Emmanuelle

    2016-01-01

    Na+/H+ exchange activity in the apical membrane of the proximal tubule is fundamental to the reabsorption of Na+ and water from the filtrate. The role of this exchange process in bicarbonate reclamation and, consequently, the maintenance of acid-base homeostasis has been appreciated for at least half a century and remains a pillar of renal tubular physiology. More recently, apical Na+/H+ exchange, mediated by Na+/H+ exchanger isoform 3 (NHE3), has been implicated in proximal tubular reabsorption of Ca2+ and Ca2+ homeostasis in general. Overexpression of NHE3 increased paracellular Ca2+ flux in a proximal tubular cell model. Consistent with this observation, mice with genetic deletion of Nhe3 have a noticable renal Ca2+ leak. These mice also display decreased intestinal Ca2+ uptake and osteopenia. This review highlights the traditional roles of proximal tubular Na+/H+ exchange and summarizes recent novel findings implicating the predominant isoform, NHE3, in Ca2+ homeostasis. PMID:23761670

  9. Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts.

    PubMed

    Donowitz, M; Janecki, A; Akhter, S; Cavet, M E; Sanchez, F; Lamprecht, G; Zizak, M; Kwon, W L; Khurana, S; Yun, C H; Tse, C M

    2000-01-01

    NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na(+)-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinases when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K'(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface biotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number. PMID:11193592

  10. Luminal Na+/H+ exchange in the proximal tubule

    PubMed Central

    Bobulescu, I. Alexandru

    2010-01-01

    The proximal tubule is critical for whole-organism volume and acid–base homeostasis by reabsorbing filtered water, NaCl, bicarbonate, and citrate, as well as by excreting acid in the form of hydrogen and ammonium ions and producing new bicarbonate in the process. Filtered organic solutes such as amino acids, oligopeptides, and proteins are also retrieved by the proximal tubule. Luminal membrane Na+/H+ exchangers either directly mediate or indirectly contribute to each of these processes. Na+/H+ exchangers are a family of secondary active transporters with diverse tissue and subcellular distributions. Two isoforms, NHE3 and NHE8, are expressed at the luminal membrane of the proximal tubule. NHE3 is the prevalent isoform in adults, is the most extensively studied, and is tightly regulated by a large number of agonists and physiological conditions acting via partially defined molecular mechanisms. Comparatively little is known about NHE8, which is highly expressed at the lumen of the neonatal proximal tubule and is mostly intracellular in adults. This article discusses the physiology of proximal Na+/H+ exchange, the multiple mechanisms of NHE3 regulation, and the reciprocal relationship between NHE3 and NHE8 at the lumen of the proximal tubule. PMID:18853182

  11. Cloning and characterization of Na(+)/H(+) Exchanger isoforms NHE2 and NHE3 from the gill of Pacific dogfish Squalus suckleyi.

    PubMed

    Guffey, Samuel C; Fliegel, Larry; Goss, Greg G

    2015-10-01

    Na(+)/H(+) Exchanger (NHE) proteins mediate cellular and systemic homeostasis of sodium and acid and may be the major sodium uptake method for fishes. We cloned and sequenced NHE2 and NHE3 from the gill of the North Pacific Spiny Dogfish shark Squalus suckleyi and expressed them in functional form in NHE-deficient (AP-1) cell lines. Estimated IC50 for inhibition of NHE activity by amiloride and EIPA were 55 μmol l(-1) and 4.8 μmol l(-1), respectively, for NHE2 and 9 μmol l(-1) and 24 μmol l(-1), respectively, for NHE3. Phenamil at 100 μmol l(-1) caused less than 16% inhibition of activity for each isoform. Although the IC50 are similar for the two isoforms, dfNHE2 is less sensitive than human NHE2 to inhibition by amiloride and EIPA, while dfNHE3 is more sensitive than human NHE3. These IC50 estimates should be considered when selecting inhibitor doses for fishes and for reinterpretation of previous studies that use these pharmacological agents. PMID:26112825

  12. Regulatory elements mediating transcription from the Drosophila melanogaster actin 5C proximal promoter.

    PubMed Central

    Chung, Y T; Keller, E B

    1990-01-01

    The major cytoskeletal actin gene of Drosophila melanogaster, the actin 5C gene, has two promoters, the proximal one of which controls constitutive synthesis of actin in all growing tissues. To locate regulatory elements required for constitutive activity of the proximal promoter, mutants of this promoter were fused to the bacterial chloramphenicol acetyltransferase gene and assayed for transient expression activity in cultured Drosophila embryonic Schneider line 2 cells. An essential regulatory element has been located 313 base pairs upstream from the cap site. Deletion of this element lowered expression to one-third of the wild-type level. The element has the sequence AAGTTGTAGTTG, as shown by protein-binding footprinting with the reagent methidiumpropyl-EDTA-Fe(II). This element is probably not a general one, since it was not detected in a search of the published 5'-flanking sequences of 27 Drosophila genes. In addition to this regulatory element, there are five GAGA elements in the actin 5C proximal promoter, some or all of which are essential for the promoter activity as shown by an in vivo competition assay. Although this promoter has no classical TATA element, there is an essential promoter region about 35 base pairs upstream from the cap site that could be a TATA surrogate. The promoter also shows sequences homologous to the alcohol dehydrogenase factor 1-binding site and to the core of the vertebrate serum response element, but mutations of these sites did not affect promoter activity in transient expression assays. Images PMID:2104658

  13. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    SciTech Connect

    Mellas, J.; Hammerman, M.R.

    1986-03-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na/sup +/-H/sup +/ exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using (/sup 14/C)-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 ..gamma.. phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular (Na/sup +/) > intracellular (Na/sup +/), was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na/sup +/-H/sup +/ exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells.

  14. Carbachol-induced MUC17 endocytosis is concomitant with NHE3 internalization and CFTR membrane recruitment in enterocytes.

    PubMed

    Pelaseyed, Thaher; Gustafsson, Jenny K; Gustafsson, Ida J; Ermund, Anna; Hansson, Gunnar C

    2013-08-15

    We have reported that transmembrane mucin MUC17 binds PDZ protein PDZK1, which retains MUC17 apically in enterocytes. MUC17 and transmembrane mucins MUC3 and MUC12 are suggested to build the enterocyte apical glycocalyx. Carbachol (CCh) stimulation of the small intestine results in gel-forming mucin secretion from goblet cells, something that requires adjacent enterocytes to secrete chloride and bicarbonate for proper mucin formation. Surface labeling and confocal imaging demonstrated that apically expressed MUC17 in Caco-2 cells and Muc3(17) in murine enterocytes were endocytosed upon stimulation with CCh. Relocation of MUC17 in response to CCh was specific as MUC3 and MUC12 did not relocate following CCh stimulation. MUC17 colocalized with PDZK1 under basal conditions, while MUC17 relocated to the terminal web and into early endosomes after CCh stimulation. CCh stimulation concomitantly internalized the Na(+/)H(+) exchanger 3 (NHE3) and recruited cystic fibrosis transmembrane conductance regulator (CFTR) to the apical membranes, a process that was important for CFTR-mediated bicarbonate secretion necessary for proper gel-forming mucin unfolding. The reason for the specific internalization of MUC17 is not understood, but it could limit the diffusion barrier for ion secretion caused by the apical enterocyte glycocalyx or alternatively act to sample luminal bacteria. Our results reveal well-orchestrated mucus secretion and trafficking of ion channels and the MUC17 mucin. PMID:23784542

  15. Differential Association of the Na+/H+ Exchanger Regulatory Factor (NHERF) Family of Adaptor Proteins with the Raft-and the Non-Raft Brush Border Membrane Fractions of NHE3

    PubMed Central

    Sultan, Ayesha; Luo, Min; Yu, Qin; Riederer, Brigitte; Xia, Weiliang; Chen, Mingmin; Lissner, Simone; Gessner, Johannes E.; Donowitz, Mark; Yun, C. Chris; deJonge, Hugo; Lamprecht, Georg; Seidler, Ursula

    2014-01-01

    Background/Aims Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM. Methods Detergent resistant membranes (“lipid rafts”) were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3− mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs. PMID:24297041

  16. Grouper tshβ Promoter-Driven Transgenic Zebrafish Marks Proximal Kidney Tubule Development

    PubMed Central

    Wang, Yang; Sun, Zhi-Hui; Zhou, Li; Li, Zhi; Gui, Jian-Fang

    2014-01-01

    Kidney tubule plays a critical role in recovering or secreting solutes, but the detailed morphogenesis remains unclear. Our previous studies have found that grouper tshβ (gtshβ) is also expressed in kidney, however, the distribution significance is still unknown. To understand the gtshβ role and kidney tubule morphogenesis, here, we have generated a transgenic zebrafish line Tg(gtshβ:GFP) with green fluorescent protein driven by the gtshβ promoter. Similar to the endogenous tshβ in zebrafish or in grouper, the gtshβ promoter-driven GFP is expressed in pituitary and kidney, and the developing details of proximal kidney tubule are marked in the transgenic zebrafish line. The gfp initially transcribes at 16 hours post fertilization (hpf) above the dorsal mesentery, and partially co-localizes with pronephric tubular markers slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal pronephric segments during embryogenesis and resides at kidney duct epithelium in adult fish. To test whether the gtshβ promoter-driven GFP may serve as a readout signal of the tubular development, we have treated the embryos with retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a distal extension of the proximal segments, while RA inhibition induces a weakness and shortness of the proximal segments. Therefore, this transgenic line provides a useful tool for genetic or chemical analysis of kidney tubule. PMID:24905828

  17. Interference in transcription of overexpressed genes by promoter-proximal downstream sequences.

    PubMed

    Turchinovich, A; Surowy, H M; Tonevitsky, A G; Burwinkel, B

    2016-01-01

    Despite a high sequence homology among four human RNAi-effectors Argonaute proteins and their coding sequences, the efficiency of ectopic overexpression of AGO3 and AGO4 coding sequences in human cells is greatly reduced as compared to AGO1 and AGO2. While investigating this phenomenon, we documented the existence of previously uncharacterized mechanism of gene expression regulation, which is manifested in greatly varying basal transcription levels from the RNApolII promoters depending on the promoter-proximal downstream sequences. Specifically, we show that distinct overexpression of Argonaute coding sequences cannot be explained by mRNA degradation in the cytoplasm or nucleus, and exhibits on transcriptional level. Furthermore, the first 1000-2000 nt located immediately downstream the promoter had the most critical influence on ectopic gene overexpression. The transcription inhibiting effect, associated with those downstream sequences, subsided with increasing distance to the promoter and positively correlated with promoter strength. We hypothesize that the same mechanism, which we named promoter proximal inhibition (PPI), could generally contribute to basal transcription levels of genes, and could be mainly responsible for the essence of difficult-to-express recombinant proteins. Finally, our data reveal that expression of recombinant proteins in human cells can be greatly enhanced by using more permissive promoter adjacent downstream sequences. PMID:27485701

  18. Interference in transcription of overexpressed genes by promoter-proximal downstream sequences

    PubMed Central

    Turchinovich, A.; Surowy, H. M.; Tonevitsky, A. G.; Burwinkel, B.

    2016-01-01

    Despite a high sequence homology among four human RNAi-effectors Argonaute proteins and their coding sequences, the efficiency of ectopic overexpression of AGO3 and AGO4 coding sequences in human cells is greatly reduced as compared to AGO1 and AGO2. While investigating this phenomenon, we documented the existence of previously uncharacterized mechanism of gene expression regulation, which is manifested in greatly varying basal transcription levels from the RNApolII promoters depending on the promoter-proximal downstream sequences. Specifically, we show that distinct overexpression of Argonaute coding sequences cannot be explained by mRNA degradation in the cytoplasm or nucleus, and exhibits on transcriptional level. Furthermore, the first 1000–2000 nt located immediately downstream the promoter had the most critical influence on ectopic gene overexpression. The transcription inhibiting effect, associated with those downstream sequences, subsided with increasing distance to the promoter and positively correlated with promoter strength. We hypothesize that the same mechanism, which we named promoter proximal inhibition (PPI), could generally contribute to basal transcription levels of genes, and could be mainly responsible for the essence of difficult-to-express recombinant proteins. Finally, our data reveal that expression of recombinant proteins in human cells can be greatly enhanced by using more permissive promoter adjacent downstream sequences. PMID:27485701

  19. In vivo evidence for interferon-gamma-mediated homeostatic mechanisms in small intestine of the NHE3 Na+/H+ exchanger knockout model of congenital diarrhea.

    PubMed

    Woo, Alison L; Gildea, Lucy A; Tack, Leslie M; Miller, Marian L; Spicer, Zachary; Millhorn, David E; Finkelman, Fred D; Hassett, Daniel J; Shull, Gary E

    2002-12-13

    Mice lacking NHE3, the major absorptive Na(+)/H(+) exchanger in the intestine, are the only animal model of congenital diarrhea. To identify molecular changes underlying compensatory mechanisms activated in chronic diarrheas, cDNA microarrays and Northern blot analyses were used to compare global mRNA expression patterns in small intestine of NHE3-deficient and wild-type mice. Among the genes identified were members of the RegIII family of growth factors, which may contribute to the increased absorptive area, and a large number of interferon-gamma-responsive genes. The latter finding is of particular interest, since interferon-gamma has been shown to regulate ion transporter activities in intestinal epithelial cells. Serum interferon-gamma was elevated 5-fold in NHE3-deficient mice; however, there was no evidence of inflammation, and unlike conditions such as inflammatory bowel disease, levels of other cytokines were unchanged. In addition, quantitative PCR analysis showed that up-regulation of interferon-gamma mRNA was localized to the small intestine and did not occur in the colon, spleen, or kidney. These in vivo data suggest that elevated interferon-gamma, produced by gut-associated lymphoid tissue in the small intestine, is part of a homeostatic mechanism that is activated in response to the intestinal absorptive defect in order to regulate the fluidity of the intestinal tract. PMID:12370192

  20. SMADs and FOXL2 synergistically regulate murine FSHbeta transcription via a conserved proximal promoter element.

    PubMed

    Tran, Stella; Lamba, Pankaj; Wang, Ying; Bernard, Daniel J

    2011-07-01

    Pituitary FSH regulates ovarian and testicular function. Activins stimulate FSHβ subunit (Fshb) gene transcription in gonadotrope cells, the rate-limiting step in mature FSH synthesis. Activin A-induced murine Fshb gene transcription in immortalized gonadotropes is dependent on homolog of Drosophila mothers against decapentaplegic (SMAD) proteins as well as the forkhead transcription factor FOXL2 (FOXL2). Here, we demonstrate that FOXL2 synergizes with SMAD2, SMAD3, and SMAD4 to stimulate murine Fshb promoter-reporter activity in heterologous cells. Moreover, SMAD3-induction of Fshb promoter activity or endogenous mRNA expression is dependent upon endogenous FOXL2 in homologous cells. FOXL2/SMAD synergy requires binding of both FOXL2 and SMAD3 or SMAD4 to DNA. Of three putative forkhead-binding elements identified in the murine Fshb promoter, only the most proximal is absolutely required for activin A induction of reporter activity in homologous cells. Additionally, mutations to the minimal SMAD-binding element adjacent to the proximal forkhead-binding element abrogate activin A or FOXL2/SMAD3 induction of reporter activity. In contrast, a mutation that impairs an adjacent PBX1/PREP1 (pre-B cell leukemia transcription factor 1-PBX/knotted-1 homeobox-1) binding site does not alter activin A-stimulated promoter activity in homologous cells. Collectively, these and previous data suggest a model in which activins stimulate formation of FOXL2-SMAD2/3/4 complexes, which bind to the proximal murine Fshb promoter to stimulate its transcription. Within these complexes, FOXL2 and SMAD3 or SMAD4 bind to adjacent cis-elements, with SMAD3 brokering the physical interaction with FOXL2. Because this composite response element is highly conserved, this suggests a general mechanism whereby activins may regulate and/or modulate Fshb transcription in mammals. PMID:21622537

  1. Retinol Promotes In Vitro Growth of Proximal Colon Organoids through a Retinoic Acid-Independent Mechanism

    PubMed Central

    Nibe, Yoichi; Akiyama, Shintaro; Matsumoto, Yuka; Nozaki, Kengo; Fukuda, Masayoshi; Hayashi, Ayumi; Mizutani, Tomohiro; Oshima, Shigeru; Watanabe, Mamoru; Nakamura, Tetsuya

    2016-01-01

    Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance. PMID:27564706

  2. Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor

    SciTech Connect

    Wang, C.-P.; Lee, Y.-F.; Chang, C.; Lee, H.-J. . E-mail: hjlee@mail.ndhu.edu.tw

    2006-12-08

    The human testicular receptor 4 (TR4) shares structural homology with members of the nuclear receptor superfamily. Some other members of this superfamily were able to regulate the transcriptional activity of the human oxytocin (OXT) promoter by binding to the first DR0 regulatory site. However, little investigation was conducted systematically in the study of the second dDR4 site of OXT proximal promoter, and the relationship between the first and the second sites of OXT promoter. Here, we demonstrated for the first time that TR4 could increase the proximal promoter activity of the human OXT gene via DR0, dDR4, and OXT (both DR0 and dDR4) elements, respectively. TR4 might induce OXT gene expression through the OXT element in a dose-dependent manner. However, there is no synergistic effect between DR0 and dDR4 elements during TR4 transactivation. Taken together, these results suggested that TR4 should be one of important regulators of OXT gene expression.

  3. Mechanisms and Developmental Roles of Promoter-proximal Pausing of RNA Polymerase II

    PubMed Central

    Robinson, Christine; Lowe, Matthew; Schwartz, Amanda; Kikyo, Nobuaki

    2016-01-01

    RNA polymerase II (Pol II) temporarily stops transcription after synthesizing 30–50 bases, and resumes elongation only after stimulations by various signaling molecules and developmental cues. This phenomenon, called promoter-proximal pausing, is observed in 10–50% of the entire genes from Drosophila embryos to human cells. Release of paused Pol II is primarily mediated by the activated form of positive transcription elongation factor b (P-TEFb) initially sequestered in the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. Many proteins and RNAs have been discovered and studied in detail to explain the process of the pausing and release of Pol II in relation to P-TEFb. At the functional level, promoter-proximal pausing regulates genes involved in stimulus-response and development in Drosophila. In mammalian stem cell biology, pausing is important for proliferation and signaling in embryonic stem cells and the formation of induced pluripotent stem cells. Other than this, however, little is known about the biological significance of pausing in mammalian cell differentiation. Further study on pausing mechanisms as well as its functions will contribute to the development of stem cell biology and its clinical applications. PMID:27158559

  4. Sal-like protein 2 upregulates p16 expression through a proximal promoter element

    PubMed Central

    Wu, Zhenghua; Cheng, Kebin; Shi, Lidan; Li, Zheqi; Negi, Hema; Gao, Guangwei; Kamle, Suchitra; Li, Dawei

    2015-01-01

    Sal-like protein 2 (Sall2), a homeotic transcription factor, is a putative tumor suppressor. We have previously shown that Sall2 activates the transcription of tumor suppressor gene p21 and suppresses tumorigenesis through cell cycle inhibition and induction of apoptosis. To investigate additional Sall2-regulated downstream genes, we analyzed the differences in mRNA expression profiles with and without exogenously expressed Sall2. We identified 1616 Sall2-responsive genes through gene expression arrays. Promoter-reporter assays of p16INK4A and several other tumor-related genes indicated that the Sall2 regulation of these promoters was not significantly different between the two major forms of Sall2 with alternative exon 1 or exon 1A. Additional analysis showed that Sall2-induced p16 promoter activation was Sall2 dose-dependent. Deletion and site-directed mutagenesis of the p16 promoter identified a consensus Sall2 binding site (GGGTGGG) proximal to the p16 transcription start site and was critical for p16 promoter activation. Finally, to confirm the significance of Sall2-activated p16 expression in cell cycle regulation, we co-transfected the SKOV3 cells with a Sall2 expression construct and a p16 minigene and also co-transfected the ES-2 cells with a Sall2 expression construct and the siRNA against p16 for flow cytometry analysis. Our results showed that Sall2 enhanced the p16 minigene blocking of cell cycle progression and p16 knockdown with siRNA abolished most of the Sall2 inhibition of cell cycle progression. These findings indicate that Sall2 targets multiple cell cycle regulators, including p16, through their promoters, adding knowledge to the understanding of Sall2 and p16 gene regulation, and how Sall2 deregulation may promote cancer formation. PMID:25580951

  5. R-loops regulate promoter-proximal chromatin architecture and cellular differentiation

    PubMed Central

    Chen, Poshen B.; Chen, Hsiuyi V.; Acharya, Diwash; Rando, Oliver J.; Fazzio, Thomas G.

    2015-01-01

    Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin regulatory complexes, Tip60–p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60–p400 histone acetyltransferase complex binds to nascent transcripts, but unlike PRC2, transcription promotes chromatin binding by Tip60–p400. Interestingly, we observed higher Tip60–p400 and lower PRC2 levels at genes marked by promoter-proximal R-loops. Furthermore, disruption of R-loops broadly reduced Tip60–p400 and increased PRC2 occupancy genome-wide. Consistent with these alterations, ESCs with reduced R-loops exhibited impaired differentiation. These results show that R-loops act both positively and negatively to modulate the recruitment of key pluripotency regulators. PMID:26551076

  6. R loops regulate promoter-proximal chromatin architecture and cellular differentiation.

    PubMed

    Chen, Poshen B; Chen, Hsiuyi V; Acharya, Diwash; Rando, Oliver J; Fazzio, Thomas G

    2015-12-01

    Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R loops, RNA-DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin-regulatory complexes, Tip60-p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60-p400 histone acetyltransferase complex binds to nascent transcripts; however, transcription promotes chromatin binding of Tip60-p400 but not PRC2. Interestingly, we observed higher Tip60-p400 and lower PRC2 levels at genes marked by promoter-proximal R loops. Furthermore, disruption of R loops broadly decreased Tip60-p400 occupancy and increased PRC2 occupancy genome wide. In agreement with these alterations, ESCs partially depleted of R loops exhibited impaired differentiation. These results show that R loops act both positively and negatively in modulating the recruitment of key pluripotency regulators. PMID:26551076

  7. Distal apolipoprotein C-III regulatory elements F to J act as a general modular enhancer for proximal promoters that contain hormone response elements. Synergism between hepatic nuclear factor-4 molecules bound to the proximal promoter and distal enhancer sites.

    PubMed

    Kardassis, D; Tzameli, I; Hadzopoulou-Cladaras, M; Talianidis, I; Zannis, V

    1997-01-01

    Transient transfection assays have shown that the distal apoC-III promoter segments that contain the regulatory elements F to J enhance the strength of the tandemly linked proximal apoA-I promoter 5- to 13-fold in hepatic (HepG2) cells. Activation in intestinal (CaCo-2) cells to levels comparable to those obtained in HepG2 cells requires a larger apoA-I promoter sequence that extends to nucleotide -1500 as well as the presence of hepatic nuclear factor-4 (HNF-4). The distal apoC-III regulatory elements can also enhance 4- to 8-fold the strength of the heterologous apoB promoter in HepG2 and CaCo-2 cells. Finally, these elements in the presence of HNF-4 enhance 14.5- to 18.5-fold the strength of the minimal adenovirus major late promoter linked to two copies of the hormone response element (HRE) AID of apoA-I in both HepG2 and CaCo-2 cells. In vitro mutagenesis of the promoter/enhancer cluster established that the enhancer activity is lost by a mutation in the HRE present in the 3' end of the regulatory element I (-736 to -714) and is reduced significantly by point mutations or deletions in one or more of the regulatory elements F to J of the apoC-III enhancer. The enhancer activity also requires the HREs of the proximal apoA-I promoter. The apoC-III enhancer can also restore the activity of the proximal apoA-I and apoB promoters that have been inactivated by mutations in CCAAT/enhancers binding protein binding sites, indicating that C/EBP may not participate in the synergistic activation of the promoter/enhancer cluster. The findings suggest that the regulatory elements F to J of the apoC-III promoter act as a general modular enhancer that can potentiate the strength of proximal promoters that contain HREs. Such potentiation in the HepG2 cells can be accounted for by synergistic interactions between HNF-4 or other nuclear hormone receptors bound to the proximal and distal HREs and SP1 or other factors bound to the apoC-III enhancer. Additional factors may be

  8. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration

    PubMed Central

    Sammarco, Mimi C.; Simkin, Jennifer; Cammack, Alexander J.; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response. PMID:26452224

  9. Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II.

    PubMed

    Lu, Xiaodong; Zhu, Xinxing; Li, You; Liu, Min; Yu, Bin; Wang, Yu; Rao, Muhua; Yang, Haiyang; Zhou, Kai; Wang, Yao; Chen, Yanheng; Chen, Meihua; Zhuang, Songkuan; Chen, Lin-Feng; Liu, Runzhong; Chen, Ruichuan

    2016-08-19

    The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network. PMID:27353326

  10. The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2-ezrin binding and dexamethasone stimulated NHE3 activity.

    PubMed

    Yang, Jianbo; Sarker, Rafiquel; Singh, Varsha; Sarker, Prateeti; Yin, Jianyi; Chen, Tian-E; Chaerkady, Raghothama; Li, Xuhang; Tse, C Ming; Donowitz, Mark

    2015-08-15

    In the brush border of intestinal and kidney epithelial cells, scaffolding proteins ezrin, Na(+)-H(+) exchanger regulatory factor (NHERF)1 and NHERF2 play important roles in linking transmembrane proteins to the cytoskeleton and assembling signalling regulatory complexes. The last 30 carboxyl residues of NHERF1 and NHERF2 form the EBDs [ezrin, radixin and moesin (ERM)-binding domain]. The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin. The EBRSs are located within 24 and 19 residues immediately upstream of EBDs for NHERF1 and NHERF2 respectively. In OK (opossum kidney) epithelial cells, EBRSs are necessary along with the EBD to distribute NHERF1 and NHERF2 exclusively to the apical domain. Furthermore, phosphorylation of Ser(303) located in the EBRS of NHERF2, decreases the binding affinity for ezrin, dislocates apical NHERF2 into the cytosol and increases the NHERF2 microvillar mobility rate. Moreover, increased phosphorylation of Ser(303) was functionally significant preventing acute stimulation of NHE3 (Na(+)-H(+) exchanger 3) activity by dexamethasone. PMID:26251448

  11. The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2–ezrin binding and dexamethasone stimulated NHE3 activity

    PubMed Central

    Yang, Jianbo; Sarker, Rafiquel; Singh, Varsha; Sarker, Prateeti; Yin, Jianyi; Chen, Tian-E; Chaerkady, Raghothama; Li, Xuhang; Tse, C. Ming; Donowitz, Mark

    2015-01-01

    In the brush border of intestinal and kidney epithelial cells, scaffolding proteins ezrin, Na+-H+ exchanger regulatory factor (NHERF)1 and NHERF2 play important roles in linking transmembrane proteins to the cytoskeleton and assembling signalling regulatory complexes. The last 30 carboxyl residues of NHERF1 and NHERF2 form the EBDs [ezrin, radixin and moesin (ERM)-binding domain]. The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin. The EBRSs are located within 24 and 19 residues immediately upstream of EBDs for NHERF1 and NHERF2 respectively. In OK (opossum kidney) epithelial cells, EBRSs are necessary along with the EBD to distribute NHERF1 and NHERF2 exclusively to the apical domain. Furthermore, phosphorylation of Ser303 located in the EBRS of NHERF2, decreases the binding affinity for ezrin, dislocates apical NHERF2 into the cytosol and increases the NHERF2 microvillar mobility rate. Moreover, increased phosphorylation of Ser303 was functionally significant preventing acute stimulation of NHE3 (Na+-H+ exchanger 3) activity by dexamethasone. PMID:26251448

  12. Trichostatin A, a histone deacetylase inhibitor stimulate CYP3A4 proximal promoter activity in Hepa-I cells.

    PubMed

    Ahn, Mee Ryung; Kim, Dae-Kee; Sheen, Yhun Yhong

    2004-04-01

    Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately 30% of the total liver CYPs contents and is involved in the metabolism of more than 60% of currently used therapeutic drugs. However, the molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-I cells were transfected with a plasmid containing approximately 1 kb of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-I cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors. PMID:15180307

  13. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice

    PubMed Central

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M.; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure—natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  14. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.

    PubMed

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  15. Profiles of embryonic nuclear protein binding to the proximal promoter region of the soybean β-conglycinin α subunit gene.

    PubMed

    Yoshino, M; Tsutsumi, K; Kanazawa, A

    2015-01-01

    β-Conglycinin, a major component of seed storage protein in soybean, comprises three subunits: α, α' and β. The expression of genes for these subunits is strictly controlled during embryogenesis. The proximal promoter region up to 245 bp upstream of the transcription start site of the α subunit gene sufficiently confers spatial and temporal control of transcription in embryos. Here, the binding profile of nuclear proteins in the proximal promoter region of the α subunit gene was analysed. DNase I footprinting analysis indicated binding of proteins to the RY element and DNA regions including box I, a region conserved in cognate gene promoters. An electrophoretic mobility shift assay (EMSA) using different portions of box I as a probe revealed that multiple portions of box I bind to nuclear proteins. In addition, an EMSA using nuclear proteins extracted from embryos at different developmental stages indicated that the levels of major DNA-protein complexes on box I increased during embryo maturation. These results are consistent with the notion that box I is important for the transcriptional control of seed storage protein genes. Furthermore, the present data suggest that nuclear proteins bind to novel motifs in box I including 5'-TCAATT-3' rather than to predicted cis-regulatory elements. PMID:24943483

  16. Hypomethylation of proximal CpG motif of interleukin-10 promoter regulates its expression in human rheumatoid arthritis

    PubMed Central

    Fu, Li-hong; Ma, Chun-ling; Cong, Bin; Li, Shu-jin; Chen, Hai-ying; Zhang, Jing-ge

    2011-01-01

    Aim: The promoter of human interleukin-10 (IL10), a cytokine crucial for suppressing inflammation and regulating immune responses, contains an interspecies-conserved sequence with CpG motifs. The aim of this study was to investigate whether methylation of CpG motifs could regulate the expression of IL10 in rheumatoid arthritis (RA). Methods: Bioinformatic analysis was conducted to identify the interspecies-conserved sequence in human, macaque and mouse IL10 genes. Peripheral blood mononuclear cells (PBMCs) from 20 RA patients and 20 health controls were collected. The PBMCs from 6 patients were cultured in the presence or absence of 5-azacytidine (5 μmol/L). The mRNA and protein levels of IL10 were examined using RT-PCR and ELISA, respectively. The methylation of CpGs in the IL10 promoter was determined by pyrosequencing. Chromatin immunoprecipitation (ChIP) assays were performed to detect the cyclic AMP response element-binding protein (CREB)-DNA interactions. Results: One interspecies-conserved sequence was found within the IL10 promoter. The upstream CpGs at −408, −387, −385, and −355 bp were hypermethylated in PBMCs from both the RA patients and healthy controls. In contrast, the proximal CpG at −145 was hypomethylated to much more extent in the RA patients than in the healthy controls (P=0.016), which was correlated with higher IL10 mRNA and serum levels. In the 5-azacytidine-treated PBMCs, the CpG motifs were demethylated, and the expression levels of IL10 mRNA and protein was significantly increased. CHIP assays revealed increased phospho-CREB binding to the IL10 promoter. Conclusion: The methylation of the proximal CpGs in the IL10 promoter may regulate gene transcription in RA. PMID:21986577

  17. Cloning of mouse telomerase reverse transcriptase gene promoter and identification of proximal core promoter sequences essential for the expression of transgenes in cancer cells.

    PubMed

    Si, Shao-Yan; Song, Shu-Jun; Zhang, Jian-Zhong; Liu, Jun-Li; Liang, Shuang; Feng, Kai; Zhao, Gang; Tan, Xiao-Qing

    2011-08-01

    Telomerase is a ribonucleoprotein complex, whose function is to add motif-specific nucleotides to the end of chromosomes. Telomerase consists of three major subunits, the telomerase RNA template (hTR), the telomerase-associated protein (TEP1) and telomerase reverse transcriptase (TERT). TERT is the most important component responsible for the catalytic activity of telomerase and a rate-limiting determinant of the activity. Telomerase activities were at high levels in approximately 90% of mouse cancers or tumor-derived cell lines through TERT transcriptional up-regulation. Unlike human telomerase, telomerase activity exists in colon, liver, ovary and testis but not in brain, heart, stomach and muscle in normal mouse tissues. In this study, we prepared 5' truncations of 1086 bp fragments upstream of the initiating ATG codon of the mTERT gene to construct luciferase reporter gene plasmids, and transfected these plasmids into a normal mouse cell line and several cancer lines to identify the core promoter region essential for transcriptional activation in cancer cells by a luciferase assay. We constructed a eukaryotic expression vector of membrane-expressing staphylococcal endotoxin A (SEA) gene driven by the core promoter region of the mTERT gene and observed if the core promoter region could express the SEA gene in these cancer cells, but not in normal cells following transfection with the construct. The results showed that the transcriptional activities of each fragment of the mTERT gene promoter in the cancer cell lines Hepa1-6, B16 and CT26 were higher than those in NIH3T3 cells, and the proximal 333-bp fragment was the core promoter of the mTERT gene in the cancer cells. The proximal 333-bp fragment was able to make the SEA express on the surface of the cancer cells, but not in NIH3T3 cells. It provides a foundation for cancer targeting gene therapy by using the mTERT gene promoter. PMID:21567104

  18. Evolution of the C4 phosphoenolpyruvate carboxylase promoter of the C4 species Flaveria trinervia: the role of the proximal promoter region

    PubMed Central

    Engelmann, Sascha; Zogel, Corinna; Koczor, Maria; Schlue, Ute; Streubel, Monika; Westhoff, Peter

    2008-01-01

    Background The key enzymes of photosynthetic carbon assimilation in C4 plants have evolved independently several times from C3 isoforms that were present in the C3 ancestral species. The C4 isoform of phosphoenolpyruvate carboxylase (PEPC), the primary CO2-fixing enzyme of the C4 cycle, is specifically expressed at high levels in mesophyll cells of the leaves of C4 species. We are interested in understanding the molecular changes that are responsible for the evolution of this C4-characteristic PEPC expression pattern, and we are using the genus Flaveria (Asteraceae) as a model system. It is known that cis-regulatory sequences for mesophyll-specific expression of the ppcA1 gene of F. trinervia (C4) are located within a distal promoter region (DR). Results In this study we focus on the proximal region (PR) of the ppcA1 promoter of F. trinervia and present an analysis of its function in establishing a C4-specific expression pattern. We demonstrate that the PR harbours cis-regulatory determinants which account for high levels of PEPC expression in the leaf. Our results further suggest that an intron in the 5' untranslated leader region of the PR is not essential for the control of ppcA1 gene expression. Conclusion The allocation of cis-regulatory elements for enhanced expression levels to the proximal region of the ppcA1 promoter provides further insight into the regulation of PEPC expression in C4 leaves. PMID:18208593

  19. Interaction of basal positive and negative transcription elements controls repression of the proximal rat prolactin promoter in nonpituitary cells.

    PubMed Central

    Jackson, S M; Keech, C A; Williamson, D J; Gutierrez-Hartmann, A

    1992-01-01

    The proximal rat prolactin (rPRL) promoter contains three cell-specific elements, designated footprints I, III, and IV, which restrict rPRL gene expression to anterior pituitary lactotroph cells. Footprint II (-130 to -120) binds a factor, which we have termed F2F, present in pituitary and nonpituitary cell types. Here we demonstrate that a key role of the footprint II site is to inhibit rPRL promoter activity in nonpituitary cells, specifically, by interfering with the basal activating function of a vicinal element. Gene transfer analysis revealed 20-fold activation of the rPRL promoter in nonpituitary cell types when footprint II was either deleted or specifically mutated. Similar activation of the intact rPRL promoter was obtained by in vivo F2F titration studies. In GH4 rat pituitary cells, the footprint II inhibitory activity was masked by the redundant, positively acting cell-specific elements and was inhibitory only if the two upstream sites, footprints III and IV, were deleted. Deletion of the -112 to -80 region in the footprint II site-specific mutant background resulted in complete loss of rPRL promoter activity in both pituitary and nonpituitary cell types, mapping a basal activating element that is operative irrespective of cell type to this region. While the basal activating element imparted an activating function in a heterologous promoter assay, the footprint II sequence did not display any inherent repressor function and actually induced several minimal heterologous promoters. However, the inhibitory activity of the footprint II site was detected only if it was in context with the basal activating element. These data underscore the importance of ubiquitous activating and inhibitory factors in establishing cell-specific gene expression and further emphasize the complexity of the molecular mechanisms which restrict gene expression to specific cell types. We provide a novel paradigm to study rPRL promoter function and hormone responsiveness

  20. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    SciTech Connect

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  1. Contribution of a Nuclear Factor-κB Binding Site to Human Angiotensinogen Promoter Activity in Renal Proximal Tubular Cells

    PubMed Central

    Acres, Omar W.; Satou, Ryousuke; Navar, L. Gabriel; Kobori, Hiroyuki

    2011-01-01

    Intrarenal angiotensinogen (AGT) is expressed highly in renal proximal tubular cells (RPTCs) and contributes to the regulation of intrarenal angiotensin II levels. Inhibition of nuclear factor (NF)-κB suppressed human (h)AGT expression in human RPTCs. However, the presence and localization of an NF-κB binding site in the hAGT promoter region have not been determined. Therefore, this study was performed to demonstrate that an NF-κB binding site in the hAGT promoter region contributes to hAGT promoter activity in human RPTCs. The hAGT promoter region was cloned from −4358 to +122 and deletion analysis was performed. A possible NF-κB binding site was removed from the hAGT promoter region (M1) and mutated (M2). Human RPTCs were transfected, and hAGT promoter activity was determined by luciferase assay. The identity of DNA binding proteins from binding assays were determined by Western blot. Progressive 5′-end deletions demonstrated removal of a distal promoter element in hAGT_−2414/+122 reduced promoter activity (0.61±0.12, ratio to hAGT_−4358/+122). Inhibition of NF-κB suppressed promoter activity in hAGT_−4358/+122 (0.51±0.14, ratio to control) and hAGT_−3681/+122 (0.48±0.06, ratio to control) but not in the construct without the NF-κB binding site. Promoter activity was reduced in the domain mutants M1 (0.57±0.08, ratio to hAGT_−4358/+122) and M2 (0.61±0.16, ratio to hAGT_−4358/+122). DNA binding levels of NF-κB protein were reduced in M1. These data demonstrate the functional importance of an NF-κB binding site in the hAGT promoter region, which contributes to hAGT promoter activity in human RPTCs. PMID:21282554

  2. Pollen specificity elements reside in 30 bp of the proximal promoters of two pollen-expressed genes.

    PubMed

    Eyal, Y; Curie, C; McCormick, S

    1995-03-01

    Functional analyses previously identified minimal promoter regions required for maintaining high-level expression of the late anther tomato LAT52 and LAT59 genes in tomato pollen. Here, we now define elements that direct pollen specificity. We used a transient assay system consisting of two cell types that differentially express the LAT genes and both "loss-of-function" and "gain-of-function" approaches. Linker substitution mutants analyzed in the transient assay and in transgenic plants identified 30-bp proximal promoter regions of LAT52 and LAT59 that are essential for their expression in pollen and that confer pollen specificity when fused to the heterologous cauliflower mosaic virus 35S core promoter. In vivo competition experiments demonstrated that a common trans-acting factor interacts with the pollen specificity region of both LAT gene promoters and suggested that a common mechanism regulates their coordinate expression. Adjacent upstream elements, the 52/56 box in LAT52 and the 56/59 box in LAT59, are involved in modulating the level of expression in pollen. The 52/56 box may be a target for the binding of a member of the GT-1 transcription factor family. PMID:7734969

  3. Pollen specificity elements reside in 30 bp of the proximal promoters of two pollen-expressed genes.

    PubMed Central

    Eyal, Y; Curie, C; McCormick, S

    1995-01-01

    Functional analyses previously identified minimal promoter regions required for maintaining high-level expression of the late anther tomato LAT52 and LAT59 genes in tomato pollen. Here, we now define elements that direct pollen specificity. We used a transient assay system consisting of two cell types that differentially express the LAT genes and both "loss-of-function" and "gain-of-function" approaches. Linker substitution mutants analyzed in the transient assay and in transgenic plants identified 30-bp proximal promoter regions of LAT52 and LAT59 that are essential for their expression in pollen and that confer pollen specificity when fused to the heterologous cauliflower mosaic virus 35S core promoter. In vivo competition experiments demonstrated that a common trans-acting factor interacts with the pollen specificity region of both LAT gene promoters and suggested that a common mechanism regulates their coordinate expression. Adjacent upstream elements, the 52/56 box in LAT52 and the 56/59 box in LAT59, are involved in modulating the level of expression in pollen. The 52/56 box may be a target for the binding of a member of the GT-1 transcription factor family. PMID:7734969

  4. Promoting Metapragmatic Development through Assessment in the Zone of Proximal Development

    ERIC Educational Resources Information Center

    van Compernolle, Remi A.; Kinginger, Celeste

    2013-01-01

    The assessment of second language (L2) pragmatic competence typically involves questionnaires, such as discourse completion tasks. This article describes a novel approach to using questionnaires to assess L2 metapragmatic capacities while simultaneously promoting their development: engaging learners in cooperative interaction as they complete the…

  5. γ-Secretase inhibition promotes fibrotic effects of albumin in proximal tubular epithelial cells

    PubMed Central

    Slattery, C; Jang, Y; Kruger, W A; Hryciw, D H; Lee, A; Poronnik, P

    2013-01-01

    Background and Purpose Albuminuria is an important biomarker of renal dysfunction and is a major mediator of renal damage and fibrosis during kidney disease. The mechanisms underlying albumin-induced renal fibrosis remain unclear. There has been significant interest in γ-secretase activity in tubular epithelial cells in recent times; however, its potential role in albumin-induced fibrosis has not been investigated. Experimental Approach The primary aim of this study was to examine the role of γ-secretase in albumin-induced fibrotic effects in proximal tubular cells. The effects of increasing albumin concentrations on fibrosis indicators and mediators in the human HK-2 cell line were examined in the presence and absence of a γ-secretase inhibitor, compound E. Key Results Treatment with albumin resulted in a number of pro-fibrotic effects, including up-regulation of fibronectin, TGF-β1 and the EGF-R. Interestingly, similar effects were observed in response to treatment with the γ-secretase inhibitor, compound E. Co-treatment of cells with albumin and an EGF-R inhibitor, AG-1478, resulted in significant inhibition of the observed pro-fibrotic effects, suggesting a major role for the EGF-R in albumin-induced fibrotic events. Albumin-induced effects on the EGF-R appeared to be mediated through inhibition of γ-secretase activity and were dependent on ERK-MAPK signalling. Conclusions and Implications These results provide novel insights into the mechanisms of albumin-induced fibrotic effects in tubular epithelial cells, suggesting important roles for the γ-secretase and the EGF-R. These results suggest that the proposed use of γ-secretase inhibitors as anti-fibrotic agents requires further investigation. PMID:23594166

  6. Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter.

    PubMed

    Fears, S; Gavin, M; Zhang, D E; Hetherington, C; Ben-David, Y; Rowley, J D; Nucifora, G

    1997-03-01

    The ETV6/CBFA2 (TEL/AML1) fusion gene occurs as a result of the chromosome translocation t(12;21)(p13;q22) in up to 30% of children diagnosed with B cell precursor (cd10+, cd19+) acute lymphoblastic leukemia. Leukemic cells that have acquired the t(12;21) usually demonstrate loss of the remaining normal ETV6 (TEL) allele. Using reporter gene assays we have functionally characterized both the normal ETV6 and ETV6/CBFA2 fusion proteins in the regulation of the MCSFR proximal promoter. Neither ETV6 or ETV6/CBFA2 has any significant, detectable effect on the promoter by itself. However, both ETV6 and ETV6/CBFA2 inhibit the activation of the promoter by CBFA2B(AML1B) and C/EBPa. We have shown that a 29-bp region of the MCSFR promoter containing the binding sites for CBFA2B and C/EBPa is sufficient for the inhibition by ETV6 and ETV6/CBFA2. Mutational analysis of the MCSFR promoter revealed that binding of both CBFA2B and C/EBPa to their respective sites is necessary for the inhibition by ETV6 and ETV6/CBFA2. Deletion of the helix-loop-helix (HLH) region from the cDNAs of ETV6 and ETV6/CBFA2 decreased but did not completely abrogate the ability of either construct to inhibit promoter activation. We also found that the ETS DNA binding region of ETV6 is necessary for inhibition of the promoter. Addition of ETS1 and FLI1, two ETS family members that have homology in the 5' HLH region, but not Spi1, an ETS family member without the 5' HLH region, also inhibited reporter gene expression. Our data show that the inhibition mediated by ETV6 and ETV6/CBFA2, in the context of the MCSFR promoter, depend on interactions with other proteins, not just CBFA2B. Our results also indicate that the transactivation characteristics of ETV6/CBFA2 are a combination of positive and negative regulatory properties. PMID:9050885

  7. NELF and GAGA Factor Are Linked to Promoter-Proximal Pausing at Many Genes in Drosophila▿ †

    PubMed Central

    Lee, Chanhyo; Li, Xiaoyong; Hechmer, Aaron; Eisen, Michael; Biggin, Mark D.; Venters, Bryan J.; Jiang, Cizhong; Li, Jian; Pugh, B. Franklin; Gilmour, David S.

    2008-01-01

    Recent analyses of RNA polymerase II (Pol II) revealed that Pol II is concentrated at the promoters of many active and inactive genes. NELF causes Pol II to pause in the promoter-proximal region of the hsp70 gene in Drosophila melanogaster. In this study, genome-wide location analysis (chromatin immunoprecipitation-microarray chip [ChIP-chip] analysis) revealed that NELF is concentrated at the 5′ ends of 2,111 genes in Drosophila cells. Permanganate genomic footprinting was used to determine if paused Pol II colocalized with NELF. Forty-six of 56 genes with NELF were found to have paused Pol II. Pol II pauses 30 to 50 nucleotides downstream from transcription start sites. Analysis of DNA sequences in the vicinity of paused Pol II identified a conserved DNA sequence that probably associates with TFIID but detected no evidence of RNA secondary structures or other conserved sequences that might directly control elongation. ChIP-chip experiments indicate that GAGA factor associates with 39% of the genes that have NELF. Surprisingly, NELF associates with almost one-half of the most highly expressed genes, indicating that NELF is not necessarily a repressor of gene expression. NELF-associated pausing of Pol II might be an obligatory but sometimes transient checkpoint during the transcription cycle. PMID:18332113

  8. Enhanced production of IL-18 in butyrate-treated intestinal epithelium by stimulation of the proximal promoter region.

    PubMed

    Kalina, Uwe; Koyama, Noriko; Hosoda, Tomoko; Nuernberger, Heike; Sato, Kazuto; Hoelzer, Dieter; Herweck, Frank; Manigold, Tobias; Singer, Manfred V; Rossol, Siegbert; Böcker, Ulrich

    2002-09-01

    Expression of IL-18 in intestinal epithelial cells (IEC) has been implicated in Th1 cell-mediated chronic intestinal inflammation and anti-tumor immunity. However, physiological regulatory factors have not been identified. Besides their effects on proliferation and restitution, immunomodulatory functions have been attributed to short chain fatty acids (SCFA). We investigated the effect of SCFA (butyrate, propionate, acetate) on expression of IL-18 in IEC in vitro and in vivo. Expression of IL-18 mRNA and protein in human carcinoma-derived HT-29 and Caco-2 cells was analyzed by reverse transcription-PCR and Western blot. Transcriptional regulation of IL-18 gene expression was determined by transient transfection of wild-type and mutated IL-18 promoter. Further, in vivo expression of IL-18 in the intestine from butyrate-treated and untreated mice was assessed by immunohistochemistry. IL-18 mRNA and the IL-18 protein were expressed in IEC, while IL-18 secretion was not observed. Butyrate and acetate increased intracellular IL-18 content in a time- and dose-dependent fashion. In contrast to proinflammatory stimuli butyrate potently activated the IL-18 promoter, indicating that IL-18 is regulated at the transcriptional level by SCFA. Furthermore, a 108-bp sequence in the proximal region was identified to be essential for IL-18 promoter activation by butyrate. As proof of principle butyrate effects were confirmed in vivo by demonstration of increased IL-18 protein expression in IEC from butyrate-treated mice. In conclusion, SCFA up-regulate IL-18 protein expression in IEC, suggesting a potential regulatory contribution of these luminal constituents to T cell mediated inflammatory and neoplastic intestinal conditions. PMID:12207348

  9. Effect of glucocorticoids on the activity, expression and proximal promoter of type II deiodinase in rat brown adipocytes.

    PubMed

    Martinez-deMena, Raquel; Calvo, Rosa-Maria; Garcia, Laura; Obregon, Maria Jesus

    2016-06-15

    Triiodothyronine (T3) is important for thermogenesis in brown adipose tissue (BAT). Type II deiodinase (DIO2) produces T3 required for intracellular needs in BAT. Brown adipocytes in culture require T3 for the adrenergic stimulation of DIO2. Glucocorticoids induce adipocyte differentiation (lipogenesis). We investigated the regulation of DIO2 activity, Dio2 mRNA and Dio2 promoter activity by glucocorticoids in primary cultures of rat brown adipocytes using dexamethasone (DEX) and hydrocortisone (HC). DEX and HC regulated the adrenergic stimulation of DIO2 activity in a dose- and time-dependent manner, inhibiting DIO2 activity at short treatment times and large doses (1-10 μM) and stimulating DIO2 at low HC doses (1-100 nM) and longer times (DEX). Insulin depletion reduced DIO2 activity but the response to glucocorticoids remained unchanged. DEX and HC inhibited basal DIO2 activity. DEX had no effect on DIO2 half-life, whereas HC stabilized DIO2 activity. DEX and HC inhibited the adrenergic stimulation of Dio2 mRNA expression (100-10000 nM, 14-96 h), but stabilized Dio2 mRNA, particularly DEX. DEX increased basal Dio2 mRNA levels, possibly through stabilization of Dio2 mRNA. An 807 bp construct of the murine Dio2 proximal promoter showed maximal reporter activity, with the cAMP response element (CRE) essential for transcriptional activity. DEX caused inhibition in most constructs containing the CRE element whereas HC stimulated reporter activity in the 807 bp construct. Glucocorticoids inhibited the adrenergic stimulation of Dio2 at the transcriptional level in brown adipocytes, although DIO2 activity increased with HC, possibly due to stabilization of Dio2 activity and mRNA. The CRE and cEBP elements of the Dio2 promoter seem involved in the regulation by glucocorticoids. PMID:26994513

  10. Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons.

    PubMed

    Jonkers, Iris; Kwak, Hojoong; Lis, John T

    2014-01-01

    Production of mRNA depends critically on the rate of RNA polymerase II (Pol II) elongation. To dissect Pol II dynamics in mouse ES cells, we inhibited Pol II transcription at either initiation or promoter-proximal pause escape with Triptolide or Flavopiridol, and tracked Pol II kinetically using GRO-seq. Both inhibitors block transcription of more than 95% of genes, showing that pause escape, like initiation, is a ubiquitous and crucial step within the transcription cycle. Moreover, paused Pol II is relatively stable, as evidenced from half-life measurements at ∼3200 genes. Finally, tracking the progression of Pol II after drug treatment establishes Pol II elongation rates at over 1000 genes. Notably, Pol II accelerates dramatically while transcribing through genes, but slows at exons. Furthermore, intergenic variance in elongation rates is substantial, and is influenced by a positive effect of H3K79me2 and negative effects of exon density and CG content within genes.DOI: http://dx.doi.org/10.7554/eLife.02407.001. PMID:24843027

  11. The proximal promoter of a novel interleukin-8-encoding gene in rainbow trout (Oncorhynchus mykiss) is strongly induced by CEBPA, but not NF-κB p65.

    PubMed

    Rebl, Alexander; Rebl, Henrike; Korytář, Tomáš; Goldammer, Tom; Seyfert, Hans-Martin

    2014-10-01

    Interleukin-8 (IL8) is an immediate-early chemokine that has been well characterized in several fish species. Ten IL8 gene variants have already been described in rainbow trout, but none of their promoters has structurally been defined or functionally characterized in teleost fish. To uncover key factors regulating IL8 expression, we intended to functionally characterize an IL8 promoter from rainbow trout. Incidentally, we isolated a novel IL8 gene variant (IL8-G). It is structurally highly similar to the other trout IL8 gene variants and its mRNA concentration increased significantly in secondary lymphoid tissues after infecting healthy fish with Aeromonas salmonicida. The proximal promoter sequence of the IL8-G-encoding gene features in close proximity two consensus elements for CEBP attachment. The proximal site overlaps with a NF-κB-binding site. Cotransfection of an IL8-G promoter-driven reporter gene together with vectors expressing various mammalian CEBP or NF-κB factors revealed in human HEK-293 cells that CEBPA and NF-κB p50, but not NF-κB p65 activate this promoter. The stimulatory effect of NF-κB p50 is likely conveyed by synergizing with CEBPA. Deletion or mutation of either the distal or the proximal CEBP-binding site, respectively, caused a significant decrease in IL8-G promoter activation. We confirmed the significance of the CEBPA factor for IL8-G expression by comparing the stimulatory capacity of the trout CEBPA and -B factors, thereby reducing the evolutionary distance in the inter-species expression assays. Similar promoter induction potential and intracellular localization of the mammalian and teleostean CEBPA and -B factors suggests their functional conservation throughout evolution. PMID:24721762

  12. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter[S

    PubMed Central

    Jeon, Bu-Nam; Kim, Yeon-Sook; Choi, Won-Il; Koh, Dong-In; Kim, Min-Kyeong; Yoon, Jae-Hyeon; Kim, Min-Young; Hur, Benjamin; Paik, Philip Dong-Hyun; Hur, Man-Wook

    2012-01-01

    Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis. PMID:22331133

  13. Identification of a non-canonical E-box motif as a regulatory element in the proximal promoter region of the apolipoprotein E gene.

    PubMed Central

    Salero, Enrique; Giménez, Cecilio; Zafra, Francisco

    2003-01-01

    We have used the yeast one-hybrid system to identify transcription factors with binding capability to specific sequences in proximal regions of the apolipoprotein E gene ( APOE ) promoter. The sequence between -113 and -80 nt, which contains regulatory elements in various cell types, was used as a bait to screen a human brain cDNA library. Four cDNA clones that encoded portions of the human upstream-stimulatory-factor (USF) transcription factor were isolated. Electrophoretic-mobility-shift assays ('EMSAs') using nuclear extracts from various human cell lines as well as from rat brain and liver revealed the formation of two DNA-protein complexes within the sequence CACCTCGTGAC (region -101/-91 of the APOE promoter) that show similarity to the E-box element. The retarded complexes contained USF1, as deduced from competition and supershift assays. Functional experiments using different APOE promoter-luciferase reporter constructs transiently transfected into U87, HepG2 or HeLa cell lines showed that mutations that precluded the formation of complexes decreased the basal activity of the promoter by about 50%. Overexpression of USF1 in U87 glioblastoma cells led to an increased activity of the promoter that was partially mediated by the atypical E-box. The stimulatory effect of USF1 was cell-type specific, as it was not observed in hepatoma HepG2 cells. Similarly, overexpression of a USF1 dominant-negative mutant decreased the basal activity of the promoter in glioblastoma, but not in hepatoma, cells. These data indicated that USF, and probably other related transcription factors, might be involved in the basal transcriptional machinery of APOE by binding to a non-canonical E-box motif within the proximal promoter. PMID:12444925

  14. Transcription activities of human papillomavirus type 11 E6 promoter-proximal elements in raft and submerged cultures of foreskin keratinocytes.

    PubMed Central

    Zhao, W; Chow, L T; Broker, T R

    1997-01-01

    Human papillomaviruses (HPVs) replicate only in differentiated squamous epithelia in warts and in epithelial raft cultures grown at the medium-air interface. Virus-encoded and host transcription factors are thought to be responsible for repressing the viral enhancer and promoter located within the upstream regulatory region (URR) in the undifferentiated basal and parabasal cells while up-regulating their activities in the differentiated spinous cells. Using recombinant retroviruses, we acutely transduced neonatal foreskin keratinocytes (PHKs) with a lacZ reporter gene driven by the wild-type URR of the low-risk HPV type 11 or by a URR with individual mutations in seven promoter-proximal elements, some of which have not been characterized previously. Beta-galactosidase activities were detected in the submerged, proliferating PHKs and also in the differentiated spinous cells, but not in the steady-state proliferating basal cells, of stratified raft cultures. In particular, mutation of an Oct1, an Sp1, or a previously unknown promoter-proximal AP1 site severely reduced the reporter activity, whereas mutation of either of two NF1 sites flanking the Oct1 site had no effect. These results demonstrate changes in cellular transcription factor profiles under different culture conditions and begin to characterize the naturally differentiation-dependent activation of the URR. They provide one molecular explanation for the patterns of HPV expression in warts and help validate epithelial raft cultures as an important experimental system for genetic dissection of HPV regulatory elements. PMID:9343243

  15. Upstream stimulatory factors, USF1 and USF2, bind to the human haem oxygenase-1 proximal promoter in vivo and regulate its transcription

    PubMed Central

    2004-01-01

    The human HO-1 (haem oxygenase-1) gene encodes a microsomal enzyme responsible for the breakdown of haem, and is also cytoprotective in response to various cellular insults. HO-1 transcription is induced by a vast array of compounds including, but certainly not limited to, haem and heavy metals such as cadmium. In the present study, we show that upstream stimulatory factors, USF1 and USF2, ubiquitous proteins belonging to the basic helix–loop–helix-leucine zipper family of transcription factors, constitutively bind to the class B E-box located in the proximal promoter of the human HO-1 gene and are responsible for the enhancement of HO-1 gene transcription in human renal proximal tubular epithelial cells. Dimethylsulphate in vivo footprinting studies have identified three protected guanine residues in the E-box of the HO-1 proximal promoter. One of these guanine contact points is essential for USF binding, and when mutated mimics a deletion mutation of the entire E-box palindrome sequence encompassing all three guanine contact points. Binding of USF1 and USF2 to the HO-1 E-box was confirmed by chromatin immunoprecipitation and gel-shift assays. Furthermore, we show that overexpression of USF1 or USF2 enhances the basal expression of HO-1 and that expression of a USF dominant negative form reduces its expression. These results demonstrate for the first time that USF proteins bind to the human HO-1 promoter in vivo and are required for high-level expression of HO-1 by haem and cadmium in human renal epithelial cells. PMID:15242350

  16. Dynamics of Cytosine Methylation in the Proximal Promoters of CYP3A4 and CYP3A7 in Pediatric and Prenatal Livers.

    PubMed

    Vyhlidal, Carrie A; Bi, Chengpeng; Ye, Shui Qing; Leeder, J Steven

    2016-07-01

    Members of the human CYP3A family of metabolizing enzymes exhibit developmental changes in expression whereby CYP3A7 is expressed in fetal tissues, followed by a transition to expression of CYP3A4 in the first months of life. Despite knowledge about the general pattern of CYP3A activity in human development, the mechanisms that regulate developmental expression remain poorly understood. Epigenetic changes, including cytosine methylation, have been suggested to play a role in the regulation of CYP3A expression. The objective of this study was to investigate changes in cytosine methylation of the CYP3A4 and CYP3A7 genes in human pediatric and prenatal livers. The methylation status of cytosine-phospho-guanine dinucleotides was determined in 16 pediatric liver samples using methyl-seq and confirmed by bisulfite sequencing of 48 pediatric and 34 prenatal liver samples. Samples were separated by age into five groups (prenatal, < 1 year of age, 1.8-6 years, 7-11 years, and 12-17 years). Methyl-seq anaylsis revealed that cytosines in the proximal promoter of CYP3A7 are hypomethylated in neonates compared with adolescents (P < 0.001). In contrast, a cytosine 383 base pair upstream of CYP3A4 is hypermethylated in liver samples from neonates compared with adolescents (P = 0.00001). Developmental changes in methylation of cytosines in the proximal promoters of CYP3A4 and CYP3A7 in pediatric livers were confirmed by bisulfite sequencing. In addition, the methylation status of cytosine in the CYP3A4 and CYP3A7 proximal promoters correlated with changes in developmental expression of mRNA for the two enzymes. PMID:26772622

  17. Uric Acid Promotes Apoptosis in Human Proximal Tubule Cells by Oxidative Stress and the Activation of NADPH Oxidase NOX 4

    PubMed Central

    Verzola, Daniela; Ratto, Elena; Villaggio, Barbara; Parodi, Emanuele Luigi; Pontremoli, Roberto; Garibotto, Giacomo; Viazzi, Francesca

    2014-01-01

    Mild hyperuricemia has been linked to the development and progression of tubulointerstitial renal damage. However the mechanisms by which uric acid may cause these effects are poorly explored. We investigated the effect of uric acid on apoptosis and the underlying mechanisms in a human proximal tubule cell line (HK-2). Increased uric acid concentration decreased tubule cell viability and increased apoptotic cells in a dose dependent manner (up to a 7-fold increase, p<0.0001). Uric acid up-regulated Bax (+60% with respect to Ctrl; p<0.05) and down regulated X-linked inhibitor of apoptosis protein. Apoptosis was blunted by Caspase-9 but not Caspase-8 inhibition. Uric acid induced changes in the mitochondrial membrane, elevations in reactive oxygen species and a pronounced up-regulation of NOX 4 mRNA and protein (p<0.05). In addition, both reactive oxygen species production and apoptosis was prevented by the NADPH oxidase inhibitor DPI as well as by Nox 4 knockdown. URAT 1 transport inhibition by probenecid and losartan and its knock down by specific siRNA, blunted apoptosis, suggesting a URAT 1 dependent cell death. In summary, our data show that uric acid increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signalling and URAT 1 transport. These results might explain the chronic tubulointerstitial damage observed in hyperuricaemic states and suggest that uric acid transport in tubular cells is necessary for urate-induced effects. PMID:25514209

  18. Characterization of the Mouse and Human Monoacylglycerol O-Acyltransferase 1 (Mogat1) Promoter in Human Kidney Proximal Tubule and Rat Liver Cells.

    PubMed

    Sankella, Shireesha; Garg, Abhimanyu; Agarwal, Anil K

    2016-01-01

    Monoacylglycerol acyltransferase 1 (Mogat1) catalyzes the conversion of monoacylglycerols (MAG) to diacylglycerols (DAG), the precursor of several physiologically important lipids such as phosphatidylcholine, phosphatidylethanolamine and triacylglycerol (TAG). Expression of Mogat1 is tissue restricted and it is highly expressed in the kidney, stomach and adipose tissue but minimally in the normal adult liver. To understand the transcriptional regulation of Mogat1, we characterized the mouse and human Mogat1 promoters in human kidney proximal tubule-2 (HK-2) cells. In-silico analysis revealed several peroxisome proliferator response element (PPRE) binding sites in the promoters of both human and mouse Mogat1. These sites responded to all three peroxisome proliferator activated receptor (PPAR) isoforms such that their respective agonist or antagonist activated or inhibited the expression of Mogat1. PPRE site mutagenesis revealed that sites located at -592 and -2518 are very effective in decreasing luciferase reporter gene activity. Chromatin immunoprecipitation (ChIP) assay using PPARα antibody further confirmed the occupancy of these sites by PPARα. While these assays revealed the core promoter elements necessary for Mogat1 expression, there are additional elements required to regulate its tissue specific expression. Chromosome conformation capture (3C) assay revealed additional cis-elements located ~10-15 kb upstream which interact with the core promoter. These chromosomal regions are responsive to both PPARα agonist and antagonist. PMID:27611931

  19. Chromatin immunoprecipitation assays revealed CREB and serine 133 phospho-CREB binding to the CART gene proximal promoter

    PubMed Central

    Rogge, George A; Shen, Li-Ling; Kuhar, Michael J.

    2010-01-01

    Both over expression of cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc), and intra-accumbal injection of cocaine- and amphetamine-regulated transcript (CART) peptides, have been shown to decrease cocaine reward. Also, over expression of CREB in the rat NAc increased CART mRNA and peptide levels, but it is not known if this was due to a direct action of P-CREB on the CART gene promoter. The goal of this study was to test if CREB and P-CREB bound directly to the CRE site in the CART promoter, using chromatin immunoprecipitation (ChIP) assays. ChIP assay with anti-CREB antibodies showed an enrichment of the CART promoter fragment containing the CRE region over IgG precipitated material, a non-specific control. Forskolin, which was known to increase CART mRNA levels in GH3 cells, was utilized to show that the drug increased levels of P-CREB protein and P-CREB binding to the CART promoter CRE-containing region. A region of the c-Fos promoter containing a CRE cis-regulatory element was previously shown to bind P-CREB, and it was used here as a positive control. These data suggest that the effects of CREB over expression on blunting cocaine reward could be, at least in part, attributed to the increased expression of the CART gene by direct interaction of P-CREB with the CART promoter CRE site, rather than by some indirect action. PMID:20451507

  20. Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

    PubMed

    Welch, W J

    2015-01-01

    Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule. PMID:25345761

  1. Proximal Nephron

    PubMed Central

    Zhuo, Jia L.; Li, Xiao C.

    2013-01-01

    The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches. PMID:23897681

  2. MIKC* MADS-Protein Complexes Bind Motifs Enriched in the Proximal Region of Late Pollen-Specific Arabidopsis Promoters[W

    PubMed Central

    Verelst, Wim; Saedler, Heinz; Münster, Thomas

    2007-01-01

    The genome of Arabidopsis (Arabidopsis thaliana) encodes over 100 MADS-domain transcription factors, categorized into five phylogenetic subgroups. Most research efforts have focused on just one of these subgroups (MIKCc), whereas the other four remain largely unexplored. Here, we report on five members of the so-called Mδ or Arabidopsis MIKC* (AtMIKC*) subgroup, which are predominantly expressed during the late stages of pollen development. Very few MADS-box genes function in mature pollen, and from this perspective, the AtMIKC* genes are therefore highly exceptional. We found that the AtMIKC* proteins are able to form multiple heterodimeric complexes in planta, and that these protein complexes exhibit a for the MADS-family unusual and high DNA binding specificity in vitro. Compared to their occurrence in promoters genome wide, AtMIKC* binding sites are strongly overrepresented in the proximal region of late pollen-specific promoters. By combining our experimental data with in silico genomics and pollen transcriptomics approaches, we identified a considerable number of putative direct target genes of the AtMIKC* transcription factor complexes in pollen, many of which have known or proposed functions in pollen tube growth. The expression of several of these predicted targets is altered in mutant pollen in which all AtMIKC* complexes are affected, and in vitro germination of this mutant pollen is severely impaired. Our data therefore suggest that the AtMIKC* protein complexes play an essential role in transcriptional regulation during late pollen development. PMID:17071640

  3. Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides

    PubMed Central

    Hanson, Melissa C.; Abraham, Wuhbet; Crespo, Monica P.; Chen, Stephanie H.; Liu, Haipeng; Szeto, Greg Lee; Kim, Mikyung; Reinherz, Ellis L.; Irvine, Darrell J.

    2015-01-01

    An HIV vaccine capable of inducing high and durable levels of broadly neutralizing antibodies has thus far proven elusive. A promising antigen is the membrane-proximal external region (MPER) from gp41, a segment of the viral envelope recognized by a number of broadly neutralizing antibodies. Though an attractive vaccine target due to the linear nature of the epitope and its highly conserved sequence, MPER peptides are poorly immunogenic and may require display on membranes to achieve a physiological conformation matching the native virus. Here we systematically explored how the structure and composition of liposomes displaying MPER peptides impacts the strength and durability of humoral responses to this antigen as well as helper T-cell responses in mice. Administration of MPER peptides anchored to the surface of liposomes induced MPER-specific antibodies whereas MPER administered in oil-based emulsion adjuvants or alum did not, even when combined with Toll like receptor agonists. High-titer IgG responses to liposomal MPER required the inclusion of molecular adjuvants such as monophosphoryl lipid A. Anti-MPER humoral responses were further enhanced by incorporating high-Tm lipids in the vesicle bilayer and optimizing the MPER density to a mean distance of ~10–15 nm between peptides on the liposomes' surfaces. Encapsulation of helper epitopes within the vesicles allowed efficient “intrastructural” T-cell help, which promoted IgG responses to MPER while minimizing competing B-cell responses against the helper sequence. These results define several key properties of liposome formulations that promote durable, high-titer antibody responses against MPER peptides, which will be a prerequisite for a successful MPER-targeting vaccine. PMID:25559188

  4. Transcriptional regulation of the PXR gene: identification and characterization of a functional peroxisome proliferator-activated receptor alpha binding site within the proximal promoter of PXR.

    PubMed

    Aouabdi, Sihem; Gibson, Gordon; Plant, Nick

    2006-01-01

    The pregnane X receptor (PXR, NR1I2) is widely regarded as a central factor in the body's response to changes in the fluxome, the overall metabolite profile in the body. PXR expression is regulated by a number of chemicals at the transcriptional level; the majority of these chemicals are ligands for PXR and substrates for PXR target genes. However, transcriptional activators of PXR, such as clofibrate, do not seem to be PXR ligands or substrates for its target genes. Understanding the molecular mechanisms underlying both these expected and, more importantly, unexpected transcriptional activations is central to fully understanding the roles of PXR in the human body. We have carried out an in silico analysis of the human PXR proximal promoter, identifying putative protein/DNA interaction sites within the 2 kilobases (kb) 5' to the putative transcription start site. These sites included several for liver-enriched transcription factors, such as the hepatic nuclear factors and CAAT-enhancer binding protein alpha, and chicken ovalbumin upstream promoter transcription factor, commensurate with the high expression of PXR in liver. Furthermore, we identified putative binding sites for a number of ligand-activated transcription factors, suggesting that these factors may regulate PXR gene expression. Further analysis of this regulatory region has shown that transcriptional activation of PXR by peroxisome proliferator-activated receptor alpha (PPARalpha) is via a binding site located approximately 1.3 kb upstream of the putative transcription start site, with ablation of this site preventing PPARalpha-mediated activation of PXR gene expression. We present a model of how regulation of PXR gene expression by ligand-activated transcription factors may play a central role in the body's response to xenobiotic exposure. PMID:16243957

  5. The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter

    PubMed Central

    Mustapic, Maja; Maihofer, Adam X.; Mahata, Manjula; Chen, Yuqing; Baker, Dewleen G.; O'Connor, Daniel T.; Nievergelt, Caroline M.

    2014-01-01

    Dopamine beta-hydroxylase (DBH) is the biosynthetic enzyme catalyzing formation of norepinephrine. Changes in DBH expression or activity have been implicated in the pathogenesis of cardiovascular and neuropsychiatric disorders. Genetic determination of DBH enzymatic activity and its secretion are only incompletely understood. We began with a genome-wide association search for loci contributing to DBH activity in human plasma. Initially, in a population sample of European ancestry, we identified the proximal DBH promoter as a region harboring three common trait-determining variants (top hit rs1611115, P = 7.2 × 10−51). We confirmed their effects on transcription and showed that the three variants each acted additively on gene expression. Results were replicated in a population sample of Native American descent (top hit rs1611115, P = 4.1 × 10−15). Jointly, DBH variants accounted for 57% of DBH trait variation. We further identified a genome-wide significant SNP at the LOC338797 locus on chromosome 12 as trans-quantitative trait locus (QTL) (rs4255618, P = 4.62 × 10−8). Conditional analyses on DBH identified a third genomic region contributing to DBH variation: a likely cis-QTL adjacent to DBH in SARDH (rs7040170, P = 1.31 × 10−14) on chromosome 9q. We conclude that three common SNPs in the DBH promoter act additively to control phenotypic variation in DBH levels, and that two additional novel loci (SARDH and LOC338797) may also contribute to the expression of this catecholamine biosynthetic trait. Identification of DBH variants with strong effects makes it possible to take advantage of Mendelian randomization approaches to test causal effects of this intermediate trait on disease. PMID:24986918

  6. Modifications of protein-DNA interactions in the proximal promoter of a cell-growth-regulated histone gene during onset and progression of osteoblast differentiation.

    PubMed Central

    Owen, T A; Holthuis, J; Markose, E; van Wijnen, A J; Wolfe, S A; Grimes, S R; Lian, J B; Stein, G S

    1990-01-01

    A temporal sequence of interrelated cellular, biochemical, and molecular events which occurs during the progressive expression of the differentiated osteoblast phenotype in primary cultures of fetal rat calvarial cells results in the development of a bone-tissue-like organization. This ordered developmental sequence encompasses three periods: proliferation, matrix maturation, and mineralization. Initially, the cells actively proliferate and synthesize type I collagen. This is followed by a period of matrix organization and maturation and then by a period of extracellular matrix mineralization. At the completion of proliferation, when expression of osteoblast phenotype markers such as alkaline phosphatase is observed, the cell-cycle-related histone genes are down-regulated transcriptionally, suggesting that a key signaling mechanism at this transition point involves modifications of protein-DNA interactions in the regulatory elements of these growth-regulated genes. Our results demonstrate that there is a selective loss of interaction of the promoter binding factor HiNF-D with the site II region of an H4 histone gene proximal promoter that regulates the specificity and level of transcription only when the down-regulation of proliferation is accompanied by modifications in the extracellular matrix that contribute to progression of osteoblast differentiation. Thus, this specific loss of protein-DNA interaction serves as a marker for a key transition point in the osteoblast developmental sequence, where the down-regulation of proliferation is functionally coupled to the appearance of osteoblast phenotypic properties associated with the organization and maturation of an extracellular matrix that becomes competent to mineralize. Images PMID:2367528

  7. Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron

    PubMed Central

    Nguyen, Mien T X; Han, Jiyang; Ralph, Donna L; Veiras, Luciana C; McDonough, Alicia A

    2015-01-01

    In Sprague Dawley rats, 2-week angiotensin II (AngII) infusion increases Na+ transporter abundance and activation from cortical thick ascending loop of Henle (TALH) to medullary collecting duct (CD) and raises blood pressure associated with a pressure natriuresis, accompanied by depressed Na+ transporter abundance and activation from proximal tubule (PT) through medullary TALH. This study tests the hypothesis that early during AngII infusion, before blood pressure raises, Na+ transporters’ abundance and activation increase all along the nephron. Male Sprague Dawley rats were infused via osmotic minipumps with a subpressor dose of AngII (200 ng/kg/min) or vehicle for 3 days. Overnight urine was collected in metabolic cages and sodium transporters’ abundance and phosphorylation were determined by immunoblotting homogenates of renal cortex and medulla. There were no significant differences in body weight gain, overnight urine volume, urinary Na+ and K+ excretion, or rate of excretion of a saline challenge between AngII and vehicle infused rats. The 3-day nonpressor AngII infusion significantly increased the abundance of PT Na+/H+ exchanger 3 (NHE3), cortical TALH Na-K-2Cl cotransporter 2 (NKCC2), distal convoluted tubule (DCT) Na-Cl cotransporter (NCC), and cortical CD ENaC subunits. Additionally, phosphorylation of cortical NKCC2, NCC, and STE20/SPS1-related proline–alanine-rich kinase (SPAK) were increased; medullary NKCC2 and SPAK were not altered. In conclusion, 3-day AngII infusion provokes PT NHE3 accumulation as well as NKCC2, NCC, and SPAK accumulation and activation in a prehypertensive phase before evidence for intrarenal angiotensinogen accumulation. PMID:26347505

  8. Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure.

    PubMed

    McDonough, Alicia A

    2010-04-01

    One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na(+) and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na(+)/H(+) exchanger isoform 3 (NHE3) and the Na(+)-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na(+) transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS. PMID:20106993

  9. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis.

    PubMed

    Laubitz, Daniel; Harrison, Christy A; Midura-Kiela, Monica T; Ramalingam, Rajalakshmy; Larmonier, Claire B; Chase, John H; Caporaso, J Gregory; Besselsen, David G; Ghishan, Fayez K; Kiela, Pawel R

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with functional inhibition of epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3), a major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for the development of dysbiosis, which promotes an exacerbated mucosal inflammatory response. Therefore, we performed a temporal analysis of gut microbiota composition, and mucosal immune response to adoptive T cell transfer was evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO) mice with and without broad-spectrum antibiotics. Microbiome (16S profiling), colonic histology, T cell and neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the most significant determinant of gut microbial community. In DKO mice, NHE3-deficiency and dysbiosis were associated with dramatically accelerated and exacerbated disease, with rapid body weight loss, increased mucosal T cell and neutrophil influx, increased mucosal cytokine expression, increased permeability, and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated by oral broad-spectrum antibiotics. Based on these results and our previous work, we postulate that epithelial electrolyte homeostasis is an important modulator in the progression of colitis, acting through remodeling of the gut microbial community. PMID:27050757

  10. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis

    PubMed Central

    Midura-Kiela, Monica T.; Ramalingam, Rajalakshmy; Larmonier, Claire B.; Chase, John H.; Caporaso, J. Gregory; Besselsen, David G.; Ghishan, Fayez K.; Kiela, Pawel R.

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with functional inhibition of epithelial Na+/H+ exchange. In mice, a selective disruption of NHE3 (Slc9a3), a major apical Na+/H+ exchanger, also promotes IBD-like symptoms and gut microbial dysbiosis. We hypothesized that disruption of Na+/H+ exchange is necessary for the development of dysbiosis, which promotes an exacerbated mucosal inflammatory response. Therefore, we performed a temporal analysis of gut microbiota composition, and mucosal immune response to adoptive T cell transfer was evaluated in Rag2-/- and NHE3-/-/Rag2-/- (DKO) mice with and without broad-spectrum antibiotics. Microbiome (16S profiling), colonic histology, T cell and neutrophil infiltration, mucosal inflammatory tone, and epithelial permeability were analyzed. In adoptive T cell transfer colitis model, Slc9a3 status was the most significant determinant of gut microbial community. In DKO mice, NHE3-deficiency and dysbiosis were associated with dramatically accelerated and exacerbated disease, with rapid body weight loss, increased mucosal T cell and neutrophil influx, increased mucosal cytokine expression, increased permeability, and expansion of CD25-FoxP3+ Tregs; this enhanced susceptibility was alleviated by oral broad-spectrum antibiotics. Based on these results and our previous work, we postulate that epithelial electrolyte homeostasis is an important modulator in the progression of colitis, acting through remodeling of the gut microbial community. PMID:27050757

  11. Proximity fuze

    DOEpatents

    Harrison, Thomas R.

    1989-08-22

    A proximity fuze system includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation cirtcuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal depending upon the light pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance form the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation.

  12. Proximity fuze

    DOEpatents

    Harrison, T.R.

    1987-07-10

    A proximity fuze system includes an optical ranging apparatus, a detonation circuit controlled by the optical ranging apparatus, and an explosive charge detonated by the detonation circuit. The optical ranging apparatus includes a pulsed laser light source for generating target ranging light pulses and optical reference light pulses. A single lens directs ranging pulses to a target and collects reflected light from the target. An optical fiber bundle is used for delaying the optical reference pulses to correspond to a predetermined distance from the target. The optical ranging apparatus includes circuitry for providing a first signal depending upon the light pulses reflected from the target, a second signal depending upon the light pulses from the optical delay fiber bundle, and an output signal when the first and second signals coincide with each other. The output signal occurs when the distance from the target is equal to the predetermined distance from the target. Additional circuitry distinguishes pulses reflected from the target from background solar radiation. 3 figs.

  13. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  14. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  15. Proximal Tibial Bone Graft

    MedlinePlus

    ... Complications Potential problems after a PTBG include infection, fracture of the proximal tibia and pain related to the procedure. Frequently Asked Questions If proximal tibial bone graft is taken from my knee, will this prevent me from being able to ...

  16. Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat.

    PubMed

    Jadlowsky, Julie K; Wong, Julian Y; Graham, Amy C; Dobrowolski, Curtis; Devor, Renee L; Adams, Mark D; Fujinaga, Koh; Karn, Jonathan

    2014-06-01

    The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown of the NELF-E subunit, a condition that induced high levels of proviral transcription in latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the 5' long terminal repeat (LTR) but not on the 3' LTR. NELF colocalizes with RNAP II, and its level increases following proviral induction. RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with high-throughput sequencing (ChIP-Seq). Like cellular promoters, RNAP II accumulates at around position +30, but HIV also shows additional pausing at +90, which is immediately downstream of a transactivation response (TAR) element and other distal sites on the HIV LTR. Following NELF-E knockdown or tumor necrosis factor alpha (TNF-α) stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. These data support a kinetic model for proviral transcription based on continuous replacement of paused RNAP II during both latency and productive transcription. In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses. PMID:24636995

  17. Negative Elongation Factor Is Required for the Maintenance of Proviral Latency but Does Not Induce Promoter-Proximal Pausing of RNA Polymerase II on the HIV Long Terminal Repeat

    PubMed Central

    Jadlowsky, Julie K.; Wong, Julian Y.; Graham, Amy C.; Dobrowolski, Curtis; Devor, Renee L.; Adams, Mark D.; Fujinaga, Koh

    2014-01-01

    The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown of the NELF-E subunit, a condition that induced high levels of proviral transcription in latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the 5′ long terminal repeat (LTR) but not on the 3′ LTR. NELF colocalizes with RNAP II, and its level increases following proviral induction. RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with high-throughput sequencing (ChIP-Seq). Like cellular promoters, RNAP II accumulates at around position +30, but HIV also shows additional pausing at +90, which is immediately downstream of a transactivation response (TAR) element and other distal sites on the HIV LTR. Following NELF-E knockdown or tumor necrosis factor alpha (TNF-α) stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. These data support a kinetic model for proviral transcription based on continuous replacement of paused RNAP II during both latency and productive transcription. In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses. PMID:24636995

  18. SUV420H2-Mediated H4K20 Trimethylation Enforces RNA Polymerase II Promoter-Proximal Pausing by Blocking hMOF-Dependent H4K16 Acetylation ▿

    PubMed Central

    Kapoor-Vazirani, Priya; Kagey, Jacob D.; Vertino, Paula M.

    2011-01-01

    Many human genes exhibit evidence of initiated RNA polymerase II (Pol II) at their promoters, despite a lack of significant full-length transcript. Such genes exhibit promoter-proximal “pausing,” wherein initiated Pol II accumulates just downstream of the transcription start site due to a rate-limiting step mediating the transition to elongation. The mechanisms that regulate the escape of Pol II from pausing and the relationship to chromatin structure remain incompletely understood. Recently, we showed that CpG island hypermethylation and epigenetic silencing of TMS1/ASC in human breast cancers are accompanied by a local shift from histone H4 lysine 16 acetylation (H4K16Ac) to H4 lysine 20 trimethylation (H4K20me3). Here, we show that hMOF-mediated H4K16Ac and SUV420H2-mediated H4K20me3 play opposing roles in the regulation of Pol II pausing. We found that H4K16Ac promoted the release of Pol II from pausing through the recruitment of BRD4 and pTEFb. Aberrant methylation of CpG island DNA blocked Pol II recruitment to gene promoters. Whereas the inhibition of DNA methylation allowed for the reassociation and initiation of Pol II at the TMS1 promoter, Pol II remained paused in the presence of H4K20me3. Combined inhibition of H4K20me3 and DNA methylation resulted in the rerecruitment of hMOF and subsequent H4K16Ac, release of Pol II into active elongation, and synergistic reactivation of TMS1 expression. Marking by H4K20me3 was not restricted to TMS1 but also occurred at other genes independently of DNA methylation, where it similarly imposed a block to Pol II promoter escape through a mechanism that involved the local inhibition of H4K16Ac. These data indicate that H4K20me3 invokes gene repression by antagonizing hMOF-mediated H4K16Ac and suggest that overcoming Pol II pausing might be a rate-limiting step in achieving tumor suppressor gene reactivation in cancer therapy. PMID:21321083

  19. Parathyroid hormone inhibition of Na{sup +}/H{sup +} exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression

    SciTech Connect

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na{sup +}/H{sup +} exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the −61 to −42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. - Highlights: • PTH regulation of Nhe3 promoter depends on EGR1 binding. • EGR1, PKA and JAK/STAT are involved in PTH inhibition of the Nhe3 promoter. • PTH alters expression of EGR1 and Sp3. • PTH inhibits the Nhe3 promoter by regulating PKA and JAK/STAT signaling.

  20. Regulation of glomerulotubular balance. III. Implication of cytosolic calcium in flow-dependent proximal tubule transport.

    PubMed

    Du, Zhaopeng; Weinbaum, Sheldon; Weinstein, Alan M; Wang, Tong

    2015-04-15

    In the proximal tubule, axial flow (drag on brush-border microvilli) stimulates Na(+) and HCO3 (-) reabsorption by modulating both Na/H exchanger 3 (NHE3) and H-ATPase activity, a process critical to glomerulotubular balance. We have also demonstrated that blocking the angiotensin II receptor decreases baseline transport, but preserves the flow effect; dopamine leaves baseline fluxes intact, but abrogates the flow effect. In the current work, we provide evidence implicating cytosolic calcium in flow-dependent transport. Mouse proximal tubules were microperfused in vitro at perfusion rates of 5 and 20 nl/min, and reabsorption of fluid (Jv) and HCO3 (-) (JHCO3) were measured. We examined the effect of high luminal Ca(2+) (5 mM), 0 mM Ca(2+), the Ca(2+) chelator BAPTA-AM, the inositol 1,4,5-trisphosphate (IP3) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB), and the Ca-ATPase inhibitor thapsigargin. In control tubules, increasing perfusion rate from 5 to 20 nl/min increased Jv by 62% and JHCO3 by 104%. With respect to Na(+) reabsorption, high luminal Ca(2+) decreased transport at low flow, but preserved the flow-induced increase; low luminal Ca(2+) had little impact; both BAPTA and 2-APB had no effect on baseline flux, but abrogated the flow effect; thapsigargin decreased baseline flow, leaving the flow effect intact. With respect to HCO3 (-) reabsorption, high luminal Ca(2+) decreased transport at low flow and mildly diminished the flow-induced increase; low luminal Ca(2+) had little impact; both BAPTA and 2-APB had no effect on baseline flux, but abrogated the flow effect. These data implicate IP3 receptor-mediated intracellular Ca(2+) signaling as a critical step in transduction of microvillous drag to modulate Na(+) and HCO3 (-) transport. PMID:25651568

  1. Proximal tibiofibular synostosis.

    PubMed

    Wong, K; Weiner, D S

    1978-09-01

    The occurrence of a proximal tibiofibular synostosis is indeed a rare condition with only 2 cases unassociated with other diseases reported to our knowledge to date. Two skeletally immature patients presented with a synostosis of the proximal tibiofibular region associated with shortening of the limb in the affected segments. Although the shortening and the synostosis seem interrelated no explanation of their relationship is evident from these 2 cases. PMID:709951

  2. Parathyroid hormone inhibition of Na(+)/H(+) exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression.

    PubMed

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na(+)/H(+) exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the -61 to -42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. PMID:25888790

  3. Capacitive proximity sensor

    DOEpatents

    Kronberg, James W.

    1994-01-01

    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  4. Capacitive proximity sensor

    DOEpatents

    Kronberg, J.W.

    1994-05-31

    A proximity sensor based on a closed field circuit is disclosed. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change. 14 figs.

  5. Unusual proximal tibiofibular synostosis.

    PubMed

    Takai, S; Yoshino, N; Hirasawa, Y

    1999-01-01

    Proximal tibiofibular synostosis without multiple hereditary exostosis is extremely rare and only 7 cases have been reported in the literature. All of the previously reported cases accompanied deformities such as distal positioning of the proximal tibiofibular joint, leg length discrepancy, bowing of the fibula, and valgus deformity of the knee. The present case of a 24-year-old man had neither a history of trauma nor deformity around the knee. Therefore, it was suggested that this type of synostosis occurred after epiphyseal plate closure. PMID:10741527

  6. Close proximity gunshot residues.

    PubMed

    Thornton, J I

    1986-04-01

    Intuitively, a hand held in close proximity to a firearm at the instant of discharge will intercept a significant amount of gunshot residue, even though the hand did not actually come into contact with the weapon. There is, however, little information specifically described in the forensic science literature concerning the residue levels which might be encountered in such an instance. The present work confirms that antimony levels consistent with an individual having fired or handled a firearm may be intercepted by a hand held in close proximity. PMID:3711843

  7. XQL and Proximal Nodes.

    ERIC Educational Resources Information Center

    Baeza-Yates, Ricardo; Navarro, Gonzalo

    2002-01-01

    Discussion of models that have been developed to structure text documents for information retrieval focuses on XML and its proposed query language XQL. Considers efficiency of the query engine and shows that an already existing model, Proximal Nodes, can be used as an efficient query engine behind an XQL front-end. (Author/LRW)

  8. Proximal tibiofibular synostosis.

    PubMed

    Gamble, J G

    1984-03-01

    A case of proximal tibiofibular synostosis with a 10-year follow-up is presented. The lesion was documented roentgenographically when the patient was 3 years of age and when she became symptomatic at 13 years of age after vigorous running. The symptoms were successfully treated with custom-molded shoe orthotics. PMID:6699166

  9. Proximate Analysis of Coal

    ERIC Educational Resources Information Center

    Donahue, Craig J.; Rais, Elizabeth A.

    2009-01-01

    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  10. Steerable Capacitive Proximity Sensor

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Steerable capacitive proximity sensor of "capaciflector" type based partly on sensing units described in GSC-13377 and GSC-13475. Position of maximum sensitivity adjusted without moving sensor. Voltage of each driven shield adjusted separately to concentrate sensing electric field more toward one side or other.

  11. Subacute diabetic proximal neuropathy

    NASA Technical Reports Server (NTRS)

    Pascoe, M. K.; Low, P. A.; Windebank, A. J.; Litchy, W. J.

    1997-01-01

    OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved

  12. Proximity Networks and Epidemics

    NASA Astrophysics Data System (ADS)

    Guclu, Hasan; Toroczkai, Zoltán

    2007-03-01

    We presented the basis of a framework to account for the dynamics of contacts in epidemic processes, through the notion of dynamic proximity graphs. By varying the integration time-parameter T, which is the period of infectivity one can give a simple account for some of the differences in the observed contact networks for different diseases, such as smallpox, or AIDS. Our simplistic model also seems to shed some light on the shape of the degree distribution of the measured people-people contact network from the EPISIM data. We certainly do not claim that the simplistic graph integration model above is a good model for dynamic contact graphs. It only contains the essential ingredients for such processes to produce a qualitative agreement with some observations. We expect that further refinements and extensions to this picture, in particular deriving the link-probabilities in the dynamic proximity graph from more realistic contact dynamics should improve the agreement between models and data.

  13. Proximal Point Methods Revisited

    NASA Astrophysics Data System (ADS)

    Boikanyo, Oganeditse A.; Moroşanu, Gheorghe

    2011-09-01

    The proximal point methods have been widely used in the last decades to approximate the solutions of nonlinear equations associated with monotone operators. Inspired by the iterative procedure defined by B. Martinet (1970), R.T. Rockafellar introduced in 1976 the so-called proximal point algorithm (PPA) for a general maximal monotone operator. The sequence generated by this iterative method is weakly convergent under appropriate conditions, but not necessarily strongly convergent, as proved by O. Güler (1991). This fact explains the introduction of different modified versions of the PPA which generate strongly convergent sequences under appropriate conditions, including the contraction-PPA defined by H.K. Xu in 2002. Here we discuss Xu's modified PPA as well as some of its generalizations. Special attention is paid to the computational errors, in particular the original Rockafellar summability assumption is replaced by the condition that the error sequence converges to zero strongly.

  14. Distributed proximity sensor system

    NASA Technical Reports Server (NTRS)

    Lee, Sukhan (Inventor)

    1988-01-01

    The invention relates to sensors embedded on the surface of a robot hand, or other moving member. By distributing proximity sensors capable of detecting distances and angles to points on the surface of an object, information is obtained for achieving noncontacting shape and distance perception, i.e., for automatic determination of the object's shape, direction, and distance, as well as the orientation of the object relative to the robot hand or other moving member.

  15. Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells.

    PubMed

    Liu, Tianbing; Konkalmatt, Prasad R; Yang, Yu; Jose, Pedro A

    2016-04-01

    The natriuretic effect of gastrin suggests a role in the coordinated regulation of sodium balance by the gastrointestinal tract and the kidney. The renal molecular targets and signal transduction pathways for such an effect of gastrin are largely unknown. Recently, we reported that gastrin induces NHE3 phosphorylation and internalization via phosphatidylinositol (PI) 3-kinase and PKCα. In this study, we show that gastrin induced the phosphorylation of human Na(+),K(+)-ATPase at serine 16, resulting in its endocytosis via Rab5 and Rab7 endosomes. The gastrin-stimulated phosphorylation of Na(+),K(+)-ATPase was dependent on PI 3-kinase because the phosphorylation was blocked by the PI 3-kinase inhibitor wortmannin. The phosphorylation of Na(+),K(+)-ATPase was also blocked by chelerythrine, a pan-PKC inhibitor, Gö-6976, a conventional PKC (cPKC) inhibitor, and BAPTA-AM, an intracellular calcium chelator, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The gastrin-mediated phosphorylation of Na(+),K(+)-ATPase was also inhibited by U-73122, a phospholipase C (PLC) inhibitor. These results suggest that gastrin regulates sodium hydrogen exchanger and pump in renal proximal tubule cells at the apical and basolateral membranes. PMID:26786777

  16. Echosonography with proximity sensors

    NASA Astrophysics Data System (ADS)

    Thaisiam, W.; Laithong, T.; Meekhun, S.; Chaiwathyothin, N.; Thanlarp, P.; Danworaphong, S.

    2013-03-01

    We propose the use of a commercial ultrasonic proximity sensor kit for profiling an altitude-varying surface by employing echosonography. The proximity sensor kit, two identical transducers together with its dedicated operating circuit, is used as a profiler for the construction of an image. Ultrasonic pulses are emitted from one of the transducers and received by the other. The time duration between the pulses allows us to determine the traveling distance of each pulse. In the experiment, the circuit is used with the addition of two copper wires for directing the outgoing and incoming signals to an oscilloscope. The time of flight of ultrasonic pulses can thus be determined. Square grids of 5 × 5 cm2 are made from fishing lines, forming pixels in the image. The grids are designed to hold the detection unit in place, about 30 cm above a flat surface. The surface to be imaged is constructed to be height varying and placed on the flat surface underneath the grids. Our result shows that an image of the profiled surface can be created by varying the location of the detection unit along the grid. We also investigate the deviation in relation to the time of flight of the ultrasonic pulse. Such an experiment should be valuable for conveying the concept of ultrasonic imaging to physical and medical science undergraduate students. Due to its simplicity, the setup could be made in any undergraduate laboratory relatively inexpensively and it requires no complex parts. The results illustrate the concept of echosonography.

  17. Proximity networks and epidemics

    NASA Astrophysics Data System (ADS)

    Toroczkai, Zoltán; Guclu, Hasan

    2007-05-01

    Disease spread in most biological populations requires the proximity of agents. In populations where the individuals have spatial mobility, the contact graph is generated by the “collision dynamics” of the agents, and thus the evolution of epidemics couples directly to the spatial dynamics of the population. We first briefly review the properties and the methodology of an agent-based simulation (EPISIMS) to model disease spread in realistic urban dynamic contact networks. Using the data generated by this simulation, we introduce the notion of dynamic proximity networks which takes into account the relevant time-scales for disease spread: contact duration, infectivity period, and rate of contact creation. This approach promises to be a good candidate for a unified treatment of epidemic types that are driven by agent collision dynamics. In particular, using a simple model, we show that it can account for the observed qualitative differences between the degree distributions of contact graphs of diseases with short infectivity period (such as air-transmitted diseases) or long infectivity periods (such as HIV).

  18. The different positioning of the proximal sequence element in the Xenopus RNA polymerase II and III snRNA promoters is a key determinant which confers RNA polymerase III specificity.

    PubMed Central

    Lescure, A; Carbon, P; Krol, A

    1991-01-01

    We and others have previously described the TATA motif as a major determinant for Pol III specificity of the U6 promoter. Surprisingly, however, the data documented here show that the sole introduction of a TATA sequence into a U1 Pol II snRNA gene is not sufficient to confer Pol III transcription. Rather, this promoter element can mediate optimal Pol III transcription only if the PSE, the second promoter element, is shifted 4 bp upstream of the position it occupies in Pol II snRNA genes. As a result, the PSE-TATA-start site spacing introduced into the U1 Pol II gene is identical to that of the U6 gene and is strictly required to produce properly initiated Pol III transcripts. Thus, Pol II and Pol III PSEs, although similar in sequence, are not positionally equivalent. Competitive experiments raise the possibility that vertebrate U6 genes contain other, as yet unidentified, promoter elements. Images PMID:2011518

  19. Some Properties of Fuzzy Soft Proximity Spaces

    PubMed Central

    Demir, İzzettin; Özbakır, Oya Bedre

    2015-01-01

    We study the fuzzy soft proximity spaces in Katsaras's sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ-neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities. PMID:25793224

  20. Tools for proximal soil sensing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proximal soil sensing (i.e. near-surface geophysical methods) are used to study soil phenomena across spatial scales. Geophysical methods exploit contrasts in physical properties (dielectric permittivity, apparent electrical conductivity or resistivity, magnetic susceptibility) to indirectly measur...

  1. Hirayama Disease with Proximal Involvement.

    PubMed

    Kim, Jinil; Kim, Yuntae; Kim, Sooa; Oh, Kiyoung

    2016-10-01

    Hirayama disease is a slowly progressing benign motor neuron disease that affects the distal upper limb. A 29-year-old man visited the hospital with a 1-year history of weakened left proximal upper limb. He was diagnosed with Hirayama disease 9 years ago, while there was no further progression of the muscle weakness afterward. Atrophy and weakness was detected in proximal upper limb muscles. Magnetic resonance imaging and somatosensory evoked potentials were normal. Needle electromyography showed abnormal findings in proximal upper limb muscles. Our patient had Hirayama disease involving the proximal portion through secondary progression. Clinical manifestation and accurate electromyography may be useful for diagnosis. Rare cases with progression patterns as described here are helpful and have clinical meaning for clinicians. PMID:27550499

  2. Cubesat Proximity Operations Demonstration (CPOD)

    NASA Technical Reports Server (NTRS)

    Villa, Marco; Martinez, Andres; Petro, Andrew

    2015-01-01

    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.

  3. Geographic Proximity and Enrollment Competition.

    ERIC Educational Resources Information Center

    Zammuto, Raymond F.

    The use of a measure of geographic proximity to help explain enrollment competition among postsecondary institutions was investigated. The measure, the number of miles between institutions, was obtained by determining the longitude and latitude coordinates for about 99% of the schools in the Higher Education General Information System universe.…

  4. Driven shielding capacitive proximity sensor

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor); McConnell, Robert L. (Inventor)

    2000-01-01

    A capacitive proximity sensing element, backed by a reflector driven at the same voltage as and in phase with the sensor, is used to reflect the field lines away from a grounded robot arm towards an intruding object, thus dramatically increasing the sensor's range and sensitivity.

  5. Fiber-optic proximity sensor

    NASA Technical Reports Server (NTRS)

    Bejczy, A. K.; Hermann, W. A.; Primus, H. C.

    1980-01-01

    Proximity sensor for mechanical hand of remote manipulator incorporates fiber optics to conduct signals between light source and light detector. Fiber optics are not prone to noise from electromagnetic interference and radio-frequency interference as are sensors using long electrical cables.

  6. Symmetry-based reciprocity: evolutionary constraints on a proximate mechanism

    PubMed Central

    Campennì, Marco

    2016-01-01

    Background. While the evolution of reciprocal cooperation has attracted an enormous attention, the proximate mechanisms underlying the ability of animals to cooperate reciprocally are comparatively neglected. Symmetry-based reciprocity is a hypothetical proximate mechanism that has been suggested to be widespread among cognitively unsophisticated animals. Methods. We developed two agent-based models of symmetry-based reciprocity (one relying on an arbitrary tag and the other on interindividual proximity) and tested their ability both to reproduce significant emergent features of cooperation in group living animals and to promote the evolution of cooperation. Results. Populations formed by agents adopting symmetry-based reciprocity showed differentiated “social relationships” and a positive correlation between cooperation given and received: two common aspects of animal cooperation. However, when reproduction and selection across multiple generations were added to the models, agents adopting symmetry-based reciprocity were outcompeted by selfish agents that never cooperated. Discussion. In order to evolve, hypothetical proximate mechanisms must be able to stand competition from alternative strategies. While the results of our simulations require confirmation using analytical methods, we provisionally suggest symmetry-based reciprocity is to be abandoned as a possible proximate mechanism underlying the ability of animals to reciprocate cooperative interactions. PMID:26998412

  7. Micropower RF material proximity sensor

    DOEpatents

    McEwan, Thomas E.

    1998-01-01

    A level detector or proximity detector for materials capable of sensing through plastic container walls or encapsulating materials is of the sensor. Thus, it can be used in corrosive environments, as well as in a wide variety of applications. An antenna has a characteristic impedance which depends on the materials in proximity to the antenna. An RF oscillator, which includes the antenna and is based on a single transistor in a Colpitt's configuration, produces an oscillating signal. A detector is coupled to the oscillator which signals changes in the oscillating signal caused by changes in the materials in proximity to the antenna. The oscillator is turned on and off at a pulse repetition frequency with a low duty cycle to conserve power. The antenna consists of a straight monopole about one-quarter wavelength long at the nominal frequency of the oscillator. The antenna may be horizontally disposed on a container and very accurately detects the fill level within the container as the material inside the container reaches the level of the antenna.

  8. Micropower RF material proximity sensor

    DOEpatents

    McEwan, T.E.

    1998-11-10

    A level detector or proximity detector for materials capable of sensing through plastic container walls or encapsulating materials is disclosed. Thus, it can be used in corrosive environments, as well as in a wide variety of applications. An antenna has a characteristic impedance which depends on the materials in proximity to the antenna. An RF oscillator, which includes the antenna and is based on a single transistor in a Colpitt`s configuration, produces an oscillating signal. A detector is coupled to the oscillator which signals changes in the oscillating signal caused by changes in the materials in proximity to the antenna. The oscillator is turned on and off at a pulse repetition frequency with a low duty cycle to conserve power. The antenna consists of a straight monopole about one-quarter wavelength long at the nominal frequency of the oscillator. The antenna may be horizontally disposed on a container and very accurately detects the fill level within the container as the material inside the container reaches the level of the antenna. 5 figs.

  9. Plating of proximal humeral fractures.

    PubMed

    Martetschläger, Frank; Siebenlist, Sebastian; Weier, Michael; Sandmann, Gunther; Ahrens, Philipp; Braun, Karl; Elser, Florian; Stöckle, Ulrich; Freude, Thomas

    2012-11-01

    The optimal treatment for proximal humeral fractures is controversial. Few data exist concerning the influence of the surgical approach on the outcome. The purpose of this study was to evaluate the clinical and radiological outcomes of proximal humeral fractures treated with locking plate fixation through a deltopectoral vs an anterolateral deltoid-splitting approach. Of 86 patients who met the inclusion criteria, 70 were available for follow-up examination. Thirty-three patients were treated through a deltopectoral approach and 37 through an anterolateral deltoid-splitting approach. In all cases, open reduction and internal fixation with a PHILOS locking plate (Synthes, Umkirch, Germany) was performed. Clinical follow-up included evaluation of pain, shoulder mobility, and strength. Constant score and Disabilities of the Arm, Shoulder and Hand (DASH) score were assessed. A clinical neurological examination of the axillary nerve was also performed. Consolidation, reduction, and appearance of head necrosis were evaluated radiographically. After a mean follow-up of 33 months, Constant scores, DASH scores, and American Shoulder and Elbow Surgeons scores showed no significant differences between the groups. Clinical neurologic examination of the axillary nerve revealed no obvious damage to the nerve in either group. Deltopectoral and anterolateral detoid-splitting approaches for plate fixation of proximal humeral fractures are safe and provide similar clinical outcomes. The results of this study suggest that the approach can be chosen according to surgeon preference. PMID:23127451

  10. Promoting Sociolinguistic Competence in the Classroom Zone of Proximal Development

    ERIC Educational Resources Information Center

    van Compernolle, Remi A.; Williams, Lawrence

    2012-01-01

    This article explores the microgenetic development of learners' understanding of sociolinguistic variation in French during an instructional conversation (IC) that followed a language analysis task in which learners attempted to formulate hypotheses about the nature of language variation. During the IC, the instructor led students toward a…

  11. Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine

    PubMed Central

    Chen, Mingmin; Sultan, Ayesha; Cinar, Ayhan; Yeruva, Sunil; Riederer, Brigitte; Singh, Anurag Kumar; Li, Junhua; Bonhagen, Janina; Chen, Gang; Yun, Chris; Donowitz, Mark; Hogema, Boris; deJonge, Hugo; Seidler, Ursula

    2010-01-01

    Trafficking and regulation of the epithelial brush border membrane (BBM) Na+/H+ exchanger 3 (NHE3) in the intestine involves interaction with four different members of the NHERF family in a signal-dependent and possibly segment-specific fashion. The aim of this research was to study the role of NHERF2 (E3KARP) in intestinal NHE3 BBM localization and second messenger-mediated and receptor-mediated inhibition of NHE3. Immunolocalization of NHE3 in WT mice revealed predominant microvillar localization in jejunum and colon, a mixed distribution in the proximal ileum but localization near the terminal web in the distal ileum. The terminal web localization of NHE3 in the distal ileum correlated with reduced acid-activated NHE3 activity (fluorometrically assessed). NHERF2 ablation resulted in a shift of NHE3 to the microvilli and higher basal fluid absorption rates in the ileum, but no change in overall NHE3 protein or mRNA expression. Forskolin-induced NHE3 inhibition was preserved in the absence of NHERF2, whereas Ca2+ ionophore- or carbachol-mediated inhibition was abolished. Likewise, Escherichia coli heat stable enterotoxin peptide (STp) lost its inhibitory effect on intestinal NHE3. It is concluded that in native murine intestine, the NHE3 adaptor protein NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal- and segment-specific fashion, and is therefore an important regulator of intestinal fluid transport. PMID:20962002

  12. Proximate and polyphenolic characterization of cranberry pomace

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The proximate composition and identification and quantification of polyphenolic compounds in dried cranberry pomace were determined. Proximate analysis was conducted based on AOAC methods for moisture, protein, fat, and ash. Total carbohydrates were determined by the difference method. Polyphenolic ...

  13. Active Targets For Capacitive Proximity Sensors

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Lightweight, low-power active targets devised for use with improved capacitive proximity sensors described in "Capacitive Proximity Sensor Has Longer Range" (GSC-13377), and "Capacitive Proximity Sensors With Additional Driven Shields" (GSC-13475). Active targets are short-distance electrostatic beacons; they generate known alternating electro-static fields used for alignment and/or to measure distances.

  14. The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na+/H+ exchanger 3 by ANG II.

    PubMed

    He, Peijian; Zhao, Luqing; No, Yi Ran; Karvar, Serhan; Yun, C Chris

    2016-08-01

    Na(+)/H(+) exchanger (NHE)3, a major Na(+) transporter in the luminal membrane of the proximal tubule, is subject to ANG II regulation in renal Na(+)/fluid absorption and blood pressure control. We have previously shown that inositol 1,4,5-trisphosphate receptor-binding protein released with inositol 1,4,5-trisphosphate (IRBIT) mediates ANG II-induced exocytosis of NHE3 in cultured proximal tubule epithelial cells. In searching for scaffold protein(s) that coordinates with IRBIT in NHE3 trafficking, we found that NHE regulatory factor (NHERF)1, NHE3, and IRBIT proteins were coexpressed in the same macrocomplexes and that loss of ANG II type 1 receptors decreased their expression in the renal brush-border membrane. We found that NHERF1 was required for ANG II-mediated forward trafficking and activation of NHE3 in cultured cells. ANG II induced a concomitant increase of NHERF1 interactions with NHE3 and IRBIT, which were abolished when the NHERF1 PDZ1 domain was removed. Overexpression of a yellow fluorescent protein-NHERF1 construct that lacks PDZ1, but not PDZ2, failed to exaggerate the ANG II-dependent increase of NHE3 expression in the apical membrane. Moreover, exogenous expression of PDZ1 exerted a dominant negative effect on NHE3 activation by ANG II. We further demonstrated that IRBIT was indispensable for the ANG II-provoked increase in NHERF1-NHE3 interactions and that phosphorylation of IRBIT at Ser(68) was necessary for the assembly of the NHEF1-IRBIT-NHE3 complex. Taken together, our findings suggest that NHERF1 mediates ANG II-induced activation of renal NHE3, which requires coordination between IRBIT and the NHERF1 PDZ1 domain in binding and transporting NHE3. PMID:27279487

  15. E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling

    PubMed Central

    Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V.

    2016-01-01

    Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling. PMID:27537838

  16. E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

    PubMed

    Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V

    2016-01-01

    Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling. PMID:27537838

  17. Proximal bodies in hypersonic flow

    SciTech Connect

    Deiterding, Ralf; Laurence, Stuart J; Hornung, Hans G

    2007-01-01

    Hypersonic flows involving two or more bodies travelling in close proximity to one another are encountered in several important situations, both natural and man-made. The present work seeks to investigate one aspect of the resulting flow problem by exploring the forces experienced by a secondary body when it is within the domain of influence of a primary body travelling at hypersonic speeds. An analytical methodology based on the blast wave analogy is developed and used to predict the secondary force coefficients for simple geometries in both two and three dimensions. When the secondary body is entirely inside the primary shocked region, the nature of the lateral force coefficient is found to depend strongly on the relative size of the two bodies. For two spheres, the methodology predicts that the secondary body will experience an exclusively attractive lateral force if the secondary diameter is larger than one-sixth the primary diameter. The analytical results are compared with those from numerical simulations and reasonable agreement is observed if an appropriate normalization for the lateral displacement is used. Results from a series of experiments in the T5 hypervelocity shock tunnel are also presented and compared with perfect-gas numerical simulations, with good agreement. A new force-measurement technique for short-duration hypersonic facilities, enabling the experimental simulation of the proximal bodies problem, is described. This technique provides two independent means of measurement, and the agreement observed between the two gives a further degree of confidence in the results obtained.

  18. Protein Neighbors and Proximity Proteomics*

    PubMed Central

    Rees, Johanna S.; Li, Xue-Wen; Perrett, Sarah; Lilley, Kathryn S.; Jackson, Antony P.

    2015-01-01

    Within cells, proteins can co-assemble into functionally integrated and spatially restricted multicomponent complexes. Often, the affinities between individual proteins are relatively weak, and proteins within such clusters may interact only indirectly with many of their other protein neighbors. This makes proteomic characterization difficult using methods such as immunoprecipitation or cross-linking. Recently, several groups have described the use of enzyme-catalyzed proximity labeling reagents that covalently tag the neighbors of a targeted protein with a small molecule such as fluorescein or biotin. The modified proteins can then be isolated by standard pulldown methods and identified by mass spectrometry. Here we will describe the techniques as well as their similarities and differences. We discuss their applications both to study protein assemblies and to provide a new way for characterizing organelle proteomes. We stress the importance of proteomic quantitation and independent target validation in such experiments. Furthermore, we suggest that there are biophysical and cell-biological principles that dictate the appropriateness of enzyme-catalyzed proximity labeling methods to address particular biological questions of interest. PMID:26355100

  19. Protein Neighbors and Proximity Proteomics.

    PubMed

    Rees, Johanna S; Li, Xue-Wen; Perrett, Sarah; Lilley, Kathryn S; Jackson, Antony P

    2015-11-01

    Within cells, proteins can co-assemble into functionally integrated and spatially restricted multicomponent complexes. Often, the affinities between individual proteins are relatively weak, and proteins within such clusters may interact only indirectly with many of their other protein neighbors. This makes proteomic characterization difficult using methods such as immunoprecipitation or cross-linking. Recently, several groups have described the use of enzyme-catalyzed proximity labeling reagents that covalently tag the neighbors of a targeted protein with a small molecule such as fluorescein or biotin. The modified proteins can then be isolated by standard pulldown methods and identified by mass spectrometry. Here we will describe the techniques as well as their similarities and differences. We discuss their applications both to study protein assemblies and to provide a new way for characterizing organelle proteomes. We stress the importance of proteomic quantitation and independent target validation in such experiments. Furthermore, we suggest that there are biophysical and cell-biological principles that dictate the appropriateness of enzyme-catalyzed proximity labeling methods to address particular biological questions of interest. PMID:26355100

  20. Resonant Frequency Spin Flipper for the nHe3 Experiment

    NASA Astrophysics Data System (ADS)

    Hayes, Christopher

    2014-03-01

    The n3He experiment, currently being installed on beamline-13 at ORNL's Spallation Neutron Source (SNS), is designed to measure the proton asymmetry associated with the interaction of neutrons with a gas of 3He via n +23He =13H +11H + 765 KeV . The experiment uses a Resonant Frequency Spin Flipper (RFSF) to flip the neutron spins. The spin flipper is similar to the one described by P.N. Seo et al. (PR ST Accel. Beams 11, 084701 2008) with significant improvements. Most important is the inclusion of a ``double cosine-theta'' winding pattern that provides a highly uniform interior field with no fringing. A critical feature of the coil is complex flux returns whose construction was made possible through the utilization of 3D print technology.

  1. Ash Aggregates in Proximal Settings

    NASA Astrophysics Data System (ADS)

    Porritt, L. A.; Russell, K.

    2012-12-01

    Ash aggregates are thought to have formed within and been deposited by the eruption column and plume and dilute density currents and their associated ash clouds. Moist, turbulent ash clouds are considered critical to ash aggregate formation by facilitating both collision and adhesion of particles. Consequently, they are most commonly found in distal deposits. Proximal deposits containing ash aggregates are less commonly observed but do occur. Here we describe two occurrences of vent proximal ash aggregate-rich deposits; the first within a kimberlite pipe where coated ash pellets and accretionary lapilli are found within the intra-vent sequence; and the second in a glaciovolcanic setting where cored pellets (armoured lapilli) occur within <1 km of the vent. The deposits within the A418 pipe, Diavik Diamond Mine, Canada, are the residual deposits within the conduit and vent of the volcano and are characterised by an abundance of ash aggregates. Coated ash pellets are dominant but are followed in abundance by ash pellets, accretionary lapilli and rare cored pellets. The coated ash pellets typically range from 1 - 5 mm in diameter and have core to rim ratios of approximately 10:1. The formation and preservation of these aggregates elucidates the style and nature of the explosive phase of kimberlite eruption at A418 (and other pipes?). First, these pyroclasts dictate the intensity of the kimberlite eruption; it must be energetic enough to cause intense fragmentation of the kimberlite to produce a substantial volume of very fine ash (<62 μm). Secondly, the ash aggregates indicate the involvement of moisture coupled with the presence of dilute expanded eruption clouds. The structure and distribution of these deposits throughout the kimberlite conduit demand that aggregation and deposition operate entirely within the confines of the vent; this indicates that aggregation is a rapid process. Ash aggregates within glaciovolcanic sequences are also rarely documented. The

  2. Efficient algorithms for proximity problems

    SciTech Connect

    Wee, Y.C.

    1989-01-01

    Computational geometry is currently a very active area of research in computer science because of its applications to VLSI design, database retrieval, robotics, pattern recognition, etc. The author studies a number of proximity problems which are fundamental in computational geometry. Optimal or improved sequential and parallel algorithms for these problems are presented. Along the way, some relations among the proximity problems are also established. Chapter 2 presents an O(N log{sup 2} N) time divide-and-conquer algorithm for solving the all pairs geographic nearest neighbors problem (GNN) for a set of N sites in the plane under any L{sub p} metric. Chapter 3 presents an O(N log N) divide-and-conquer algorithm for computing the angle restricted Voronoi diagram for a set of N sites in the plane. Chapter 4 introduces a new data structure for the dynamic version of GNN. Chapter 5 defines a new formalism called the quasi-valid range aggregation. This formalism leads to a new and simple method for reducing non-range query-like problems to range queries and often to orthogonal range queries, with immediate applications to the attracted neighbor and the planar all-pairs nearest neighbors problem. Chapter 6 introduces a new approach for the construction of the Voronoi diagram. Using this approach, we design an O(log N) time O (N) processor algorithm for constructing the Voronoi diagram with L{sub 1} and L. metrics on a CREW PRAM machine. Even though the GNN and the Delaunay triangulation (DT) do not have an inclusion relation, we show, using some range type queries, how to efficiently construct DT from the GNN relations over a constant number of angular ranges.

  3. Human Promoters Are Intrinsically Directional

    PubMed Central

    Duttke, Sascha H.C.; Lacadie, Scott A.; Ibrahim, Mahmoud M.; Glass, Christopher K.; Corcoran, David L.; Benner, Christopher; Heinz, Sven; Kadonaga, James T.; Ohler, Uwe

    2015-01-01

    Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that up to half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. PMID:25639469

  4. Renin expression in renal proximal tubule.

    PubMed Central

    Moe, O W; Ujiie, K; Star, R A; Miller, R T; Widell, J; Alpern, R J; Henrich, W L

    1993-01-01

    Angiotensinogen, angiotensin-converting enzyme, and renin constitute the components of the renin-angiotensin system. The mammalian renal proximal tubule contains angiotensinogen, angiotensin-converting enzyme, and angiotensin receptors. Previous immunohistochemical studies describing the presence of renin in the proximal tubule could not distinguish synthesized renin from renin trapped from the glomerular filtrate. In the present study, we examined the presence of renin activity and mRNA in rabbit proximal tubule cells in primary culture and renin mRNA in microdissected proximal tubules. Renin activity was present in lysates of proximal tubule cells in primary culture. Cellular renin content in cultured proximal tubule cells was increased by incubation with 10(-5) M isoproterenol and 10(-5) M forskolin by 150 and 110%, respectively. In addition, renin transcripts were detected in poly(A)+ RNA from cultured proximal tubule cells by RNA blots under high stringency conditions. In microdissected tubules from normal rats, renin mRNA was not detectable with reverse transcription and polymerase chain reaction. However, in tubules from rats administered the angiotensinogen-converting-enzyme inhibitor, enalapril, renin was easily detected in the S2 segment of the proximal tubule. We postulate the existence of a local renin-angiotensin system that enables the proximal tubule to generate angiotensin II, thereby providing an autocrine system that could locally modulate NaHCO3 and NaCl absorption. Images PMID:7680667

  5. Range gated strip proximity sensor

    DOEpatents

    McEwan, T.E.

    1996-12-03

    A range gated strip proximity sensor uses one set of sensor electronics and a distributed antenna or strip which extends along the perimeter to be sensed. A micro-power RF transmitter is coupled to the first end of the strip and transmits a sequence of RF pulses on the strip to produce a sensor field along the strip. A receiver is coupled to the second end of the strip, and generates a field reference signal in response to the sequence of pulse on the line combined with received electromagnetic energy from reflections in the field. The sensor signals comprise pulses of radio frequency signals having a duration of less than 10 nanoseconds, and a pulse repetition rate on the order of 1 to 10 MegaHertz or less. The duration of the radio frequency pulses is adjusted to control the range of the sensor. An RF detector feeds a filter capacitor in response to received pulses on the strip line to produce a field reference signal representing the average amplitude of the received pulses. When a received pulse is mixed with a received echo, the mixing causes a fluctuation in the amplitude of the field reference signal, providing a range-limited Doppler type signature of a field disturbance. 6 figs.

  6. Range gated strip proximity sensor

    DOEpatents

    McEwan, Thomas E.

    1996-01-01

    A range gated strip proximity sensor uses one set of sensor electronics and a distributed antenna or strip which extends along the perimeter to be sensed. A micro-power RF transmitter is coupled to the first end of the strip and transmits a sequence of RF pulses on the strip to produce a sensor field along the strip. A receiver is coupled to the second end of the strip, and generates a field reference signal in response to the sequence of pulse on the line combined with received electromagnetic energy from reflections in the field. The sensor signals comprise pulses of radio frequency signals having a duration of less than 10 nanoseconds, and a pulse repetition rate on the order of 1 to 10 MegaHertz or less. The duration of the radio frequency pulses is adjusted to control the range of the sensor. An RF detector feeds a filter capacitor in response to received pulses on the strip line to produce a field reference signal representing the average amplitude of the received pulses. When a received pulse is mixed with a received echo, the mixing causes a fluctuation in the amplitude of the field reference signal, providing a range-limited Doppler type signature of a field disturbance.

  7. Optical proximity sensors for manipulators

    NASA Technical Reports Server (NTRS)

    Johnson, A. R.

    1973-01-01

    A breadboard optical proximity sensor intended for application to remotely operated manipulators has been constructed and evaluated in the laboratory. The sensing head was 20 mm x 15 mm x 10 mm in size, and could be made considerably smaller. Several such devices could be conveniently mounted on a manipulator hand, for example, to align the hand with an object. Type 1 and Type 2 optical configurations are discussed, Type 1 having a sharply defined sensitive volume, Type 2 an extended one. The sensitive volume can be placed at any distance between 1 cm and approximately 1 m by choice of a replaceable prism. The Type 1 lateral resolution was 0.5 mm on one axis and 5 mm perpendicular to it for a unit focused at 7.5 cm. The corresponding resolution in the axial direction was 2.4 cm, but improvement to 0.5 cm is possible. The effect of surface reflectivity is discussed and possible modes of application are suggested.

  8. Proximal Priority Laser Therapy: PPLT

    NASA Astrophysics Data System (ADS)

    Ohshiro, Toshio

    2004-09-01

    The author has, in the past, classified treatment methods for pain geometrically as point, line, two-dimensional, three-dimensional treatment and has used these over the years. However as a practitioner of western medicine, the author originally treated pain only directed at the painful site, and encountered cases where local treatment did not suffice. The author proved with SPECT and the Rand Phantom that treating the neck which is the midpoint of the brain, the center of the nervous system and the heart, the center of circulation, increased cerebral blood flow and also that laser emitted to neck will reach the spinal chord no matter from where on the neck the laser is emitted. From such research and 25 years of clinical experience, the author has created an anatomy based, systemic treatment method called the Proximal Priority Laser Therapy (PPLT) where not only the cerebral cortex, spinal chord and peripheral nerves are treated but also the tracts of blood vessels and lymph ducts are treated as well. Treatment method and cases are presented herein.

  9. Reticle processing induced proximity effects

    NASA Astrophysics Data System (ADS)

    Janssen, Maurice; de Kruif, Robert; Kiers, Ton

    2002-08-01

    Minimising Across Retical Line width Variation is a continuous challenge for each resolution node. Having tight critical dimension (CD) uniformity for a large variety of pitches is even more challenging. The causes of the reticle errors originate mainly from writing reticles at the edge of the write-tool's capabilities, and from manufacturing at the edge of etching and processing capabilities. These various reticle errors will subsequently lead to non-uniformity effects on wafer level. The reticle errors can be compensated for using technologies similar to those used to correct for optical proximity effects at wafer level. The errors can be small effects in the nanometer range like write noise or larger effects of 10 nm to 100 nm on reticle level from etching. Many effects that we see on reticle will be made visible on the wafer after exposure on a Step & Scan system. To visualise system performance one can use specific techniques such as selection of lines that are on target. In addition, with extensive measurement these reticle errors can be subtracted and thus removed from the final wafer result. For the investigation use is made of a reticle, which has a variation of 35 pitches for four line widths of 100 nm, 130 nm, 150 nm, and 170 nm at 1X. The reticle underwent extensive measurements, and its characteristics are described from these measurements. In addition, some wafer results are shown.

  10. Proximal Participation: A Pathway into Work

    ERIC Educational Resources Information Center

    Chan, Selena

    2013-01-01

    In a longitudinal case study of apprentices, the term proximal participation was coined to describe the entry process of young people, with unclear career destinations, into the trade of baking. This article unravels the significance of proximal participation in the decision-making processes of young people who enter a trade through initial…

  11. Proximate Sources of Collective Teacher Efficacy

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.

    2006-01-01

    Purpose: Recent scholarship has augmented Bandura's theory underlying efficacy formation by pointing to more proximate sources of efficacy information involved in forming collective teacher efficacy. These proximate sources of efficacy information theoretically shape a teacher's perception of the teaching context, operationalizing the difficulty…

  12. Proximal bodies in hypersonic flow

    NASA Astrophysics Data System (ADS)

    Laurence, Stuart J.

    The problem of proximal bodies in hypersonic flow is encountered in several important situations, both natural and man-made. The present work seeks to investigate one aspect of this problem by exploring the forces experienced by a secondary body when some part of it is within the shocked region created by a primary body travelling at hypersonic speeds. An analytical methodology based on the blast wave analogy is developed and used to predict the secondary force coefficients for simple geometries in both two and three dimensions. When the secondary body is entirely inside the primary shocked region, the nature of the lateral coefficient is found to depend strongly on the relative size of the two bodies. For two spheres, the methodology predicts that the secondary body will experience an exclusively attractive lateral force if the secondary diameter is larger then one-sixth the primary diameter. The analytical results are compared with numerical simulations carried out using the AMROC software and good agreement is obtained if an appropriate normalization for the lateral displacement is used. Results from a series of experiments in the T5 hypervelocity shock tunnel are also presented and compared with perfect-gas numerical simulations, again with good agreement. In order to model this situation experimentally, a new force-measurement technique for short-duration hypersonic facilities has been developed, and results from the validation experiments are included. Finally, the analytical methodology is used to model two physical situations. First, the entry of a binary asteroid system into the Earth's atmosphere is simulated. Second, a model for a fragmenting meteoroid in a planetary atmosphere is developed, and simulations are carried out to determine whether the secondary scatter patterns in the Sikhote-Alin crater field may be attributed to aerodynamic interactions between fragments rather than to secondary fragmentation. It is found that while aerodynamic

  13. Design and ground verification of proximity operations

    NASA Astrophysics Data System (ADS)

    Tobias, A.; Ankersen, F.; Fehse, W.; Pauvert, C.; Pairot, J.

    This paper describes the approach to guidance, navigation, and control (GNC) design and verification for proximity operations. The most critical part of the rendezvous mission is the proximity operations phase when the distance between chaser and target is below approximately 20 m. Safety is the overriding consideration in the design of the GNC system. Requirements on the GNC system also stem from the allocation of performance between proximity operations and the mating process, docking, or capture for berthing. Whereas the design process follows a top down approach, the verification process goes bottom up in a stepwise way according to the development stage.

  14. [Proximity, intimacy and promiscuity in care].

    PubMed

    Flicourt, Nadia

    2015-04-01

    Lying at the heart of the intimacy of the other person, the nature of care supposes that the caregiver identifies the components resulting from the proximity and the invasion of the patient's personal space, where perceptions and representations give rise to reactive emotions and behaviour. Between modesty and nudity, proximity and promiscuity, caregivers have to adjust their approach of proper care, limiting the risks of intrusion. PMID:26043630

  15. An evaluation of proximal surface cleansing agents.

    PubMed

    Wolffe, G N

    1976-08-01

    The effectiveness of the Interspace brush, Inter-Dens, and waxed dental floss as proximal surface cleansing agents was compared in 35 subjects. Each subject used all three methods of cleansing in random order of selection. Statistical analysis of the results showed that there was no difference in the effectiveness of any one of these three agents. However, proximal surfaces of anterior teeth where cleaned more effectively than posterior teeth. The coronal half of the proximal surfaces was cleaned more effectively than the apical half and the facial half more effectively than the lingual half when Inter-Dens was used. Comparison of cleansing effectiveness between facial and lingual halves of proximal surfaces for the Interspace brush and waxed dental floss showed no significant difference. Mesial and distal proximal surfaces were cleaned with similar effectiveness. Plaque control was only satisfactory on approximately half of the proximal surfaces, though a wide variation occurred. Significantly lower plaque scores were found 1 week after the initial instruction session, irrespective of the agent used. The majority of subjects preferred Inter-Dens whilst waxed dental floss was the least-liked method of cleansing. PMID:1067276

  16. Proximity sensor system development. CRADA final report

    SciTech Connect

    Haley, D.C.; Pigoski, T.M.

    1998-01-01

    Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.

  17. Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld

    ERIC Educational Resources Information Center

    Ferholt, Beth; Lecusay, Robert

    2010-01-01

    This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…

  18. Proximal Junctional Kyphosis: Diagnosis, Pathogenesis, and Treatment

    PubMed Central

    Lee, Jaewon

    2016-01-01

    Proximal junctional kyphosis (PJK) is a common radiographic finding after long spinal fusion. A number of studies on the causes, risk factors, prevention, and treatment of PJK have been conducted. However, no clear definition of PJK has been established. In this paper, we aimed to clarify the diagnosis, prevention, and treatment of PJK by reviewing relevant papers that have been published to date. A literature search was conducted on PubMed using "proximal junctional", "proximal junctional kyphosis", and "proximal junctional failure" as search keywords. Only studies that were published in English were included in this study. The incidence of PJK ranges from 5% to 46%, and it has been reported that 66% of cases occur 3 months after surgery and approximately 80% occur within 18 months. A number of studies have reported that there is no significantly different clinical outcome between PJK patients and non-PJK patients. One study showed that PJK patients expressed more pain than non-PJK patients. However, recent studies focused on proximal junctional failure (PJF), which is accepted as a severe form of PJK. PJF showed significant adverse impact in clinical aspect such as pain, neurologic deficit, ambulatory difficulties, and social isolation. Numerous previous studies have identified various risk factors and reported on the treatment and prevention of PJK. Based on these studies, we determined the clinical significance and impact of PJK. In addition, it is important to find a strategic approach to the proper treatment of PJK. PMID:27340542

  19. Proximity assays for sensitive quantification of proteins.

    PubMed

    Greenwood, Christina; Ruff, David; Kirvell, Sara; Johnson, Gemma; Dhillon, Harvinder S; Bustin, Stephen A

    2015-06-01

    Proximity assays are immunohistochemical tools that utilise two or more DNA-tagged aptamers or antibodies binding in close proximity to the same protein or protein complex. Amplification by PCR or isothermal methods and hybridisation of a labelled probe to its DNA target generates a signal that enables sensitive and robust detection of proteins, protein modifications or protein-protein interactions. Assays can be carried out in homogeneous or solid phase formats and in situ assays can visualise single protein molecules or complexes with high spatial accuracy. These properties highlight the potential of proximity assays in research, diagnostic, pharmacological and many other applications that require sensitive, specific and accurate assessments of protein expression. PMID:27077033

  20. Jet Diffusion in Proximity of a Wall

    NASA Technical Reports Server (NTRS)

    Kuechemann, D.

    1949-01-01

    When auxiliary jet engines are installed on airframes; as well as in some new designs, the jet engines are mounted in such a way that the jet stream exhausts in close proximity to the fuselage. This report deals with the behavior of the jet in close proximity to a two-dimensional surface. The experiments were made to find out whether the axially symmetric stream tends to approach the flat surface. This report is the last of a series of four partial test reports of the Goettingen program for the installation of jet engines, dated October 12, 1943. This report is the complement of the report on intake in close proximity to a wall.

  1. Proximity assays for sensitive quantification of proteins

    PubMed Central

    Greenwood, Christina; Ruff, David; Kirvell, Sara; Johnson, Gemma; Dhillon, Harvinder S.; Bustin, Stephen A.

    2015-01-01

    Proximity assays are immunohistochemical tools that utilise two or more DNA-tagged aptamers or antibodies binding in close proximity to the same protein or protein complex. Amplification by PCR or isothermal methods and hybridisation of a labelled probe to its DNA target generates a signal that enables sensitive and robust detection of proteins, protein modifications or protein–protein interactions. Assays can be carried out in homogeneous or solid phase formats and in situ assays can visualise single protein molecules or complexes with high spatial accuracy. These properties highlight the potential of proximity assays in research, diagnostic, pharmacological and many other applications that require sensitive, specific and accurate assessments of protein expression. PMID:27077033

  2. Infrared-Proximity-Sensor Modules For Robot

    NASA Technical Reports Server (NTRS)

    Parton, William; Wegerif, Daniel; Rosinski, Douglas

    1995-01-01

    Collision-avoidance system for articulated robot manipulators uses infrared proximity sensors grouped together in array of sensor modules. Sensor modules, called "sensorCells," distributed processing board-level products for acquiring data from proximity-sensors strategically mounted on robot manipulators. Each sensorCell self-contained and consists of multiple sensing elements, discrete electronics, microcontroller and communications components. Modules connected to central control computer by redundant serial digital communication subsystem including both serial and a multi-drop bus. Detects objects made of various materials at distance of up to 50 cm. For some materials, such as thermal protection system tiles, detection range reduced to approximately 20 cm.

  3. Laparoscopic Proximal Gastrectomy With Gastric Tube Reconstruction

    PubMed Central

    Shiraishi, Norio; Toujigamori, Manabu; Shiroshita, Hidefumi; Etoh, Tsuyoshi; Inomata, Masafumi

    2016-01-01

    Background and Objectives: There is no standardized method of reconstruction in laparoscopic proximal gastrectomy (LPG). We present a novel technique of reconstruction with a long, narrow gastric tube in LPG for early gastric cancer (EGC). Methods: During the laparoscopic procedure, the upper part of the stomach is fully mobilized with perigastric and suprapancreatic lymphadenectomy, and then the abdominal esophagus is transected. After a minilaparotomy is created, the entire stomach is pulled outside. A long, narrow gastric tube (20 cm long, 3 cm wide) is created with a linear stapler. The proximal part of the gastric tube is formed into a cobra head shape for esophagogastric tube anastomosis, which is then performed with a 45-mm linear stapler under laparoscopic view. The end of the esophagus is fixed on the gastric tube to prevent postoperative esophageal reflux. Results: Thirteen patients with early proximal gastric cancer underwent the procedure. The mean operative time was 283 min, and median blood loss was 63 ml. There were no conversions to open surgery, and no intraoperative complications. Conclusion: This new technique of reconstruction after LPG is simple and feasible. The procedure has the potential of becoming a standard reconstruction technique after LPG for proximal EGC. PMID:27547027

  4. Current status of proximal gastric vagotomy.

    PubMed Central

    Schirmer, B D

    1989-01-01

    Proximal gastric vagotomy is nearing its twentieth year in clinical use as an operation for peptic ulcer disease. No other acid-reducing operation has undergone as much scrutiny or study. At this time, the evidence of such studies and long-term follow-up strongly supports the use of proximal gastric vagotomy as the treatment of choice for chronic duodenal ulcer in patients who have failed medical therapy. Its application in treating the complications of peptic ulcer disease, which recently have come to represent an increasingly greater percentage of all operations done for peptic ulcer disease, is well-tested. However, initial series suggest that it should probably occupy a prominent role in treating some of these complications, particularly in selected patients, in the future. The operation has the well-documented ability to reduce gastric acid production, not inhibit gastric bicarbonate production, and also minimally inhibit gastric motility. The combination of these physiologic results after proximal gastric vagotomy, along with preservation of the normal antropyloroduodenal mechanism of gastrointestinal control, serve to allow patients with proximal gastric vagotomy the improved benefits of significantly fewer severe gastrointestinal side effects than are seen after other operations for peptic ulcer disease. PMID:2644897

  5. Hybrid Repair of Proximal Subclavian Artery Aneurysm

    PubMed Central

    Morimoto, Kazuki; Fukuda, Tetsuya; Iba, Hiroshi; Tanaka, Hiroshi; Sasaki, Hiroaki; Minatoya, Kenji; Kobayashi, Junjiro

    2015-01-01

    Objective: Conventional open repair for proximal subclavian artery aneurysms (SCAAs) requires cardiopulmonary bypass. However, patients with proximal SCAA can be treated with hybrid repair. Methods: Between 2007 and 2012, we performed hybrid repair to treat six consecutive patients with proximal SCAA (three left SCAAs, one right aberrant SCAA, two right SCAAs). Their median age was 73.5 [70–87] years, and the size of their aneurysm was 33.5 [30–45] mm. Thoracic endovascular aneurysm repair (TEVAR) only was used for one patient with left SCAA, TEVAR and supra-aortic bypass for two with left SCAA and one with right aberrant SCAA, and endovascular repair with reconstruction of the vertebral artery using the saphenous vein graft (SVG) for two with right SCAA. Results: The follow-up duration was 3.7 [0.2–6.8] years. There was no 30-day mortality and only one early complication consisting of a minor stroke after TEVAR for shaggy aorta. Two late deaths occurred, one caused by cerebral infarction due to occlusion of SVG to the dominant vertebral artery 2 months after the operation and the other by aortic dissection 5 years postoperatively. Conclusions: Hybrid repair can be a less-invasive alternative for proximal SCAA. Revascularization of neck vessels and TEVAR should be performed very carefully to prevent neurologic complications. PMID:26131027

  6. Traumatic proximal tibiofibular dislocation with neurovascular injury

    PubMed Central

    Veerappa, Lokesh A; Gopalakrishna, Chetan

    2012-01-01

    23 years old male presented with inferolateral dislocation of proximal tibiofibular joint associated with popliteal artery and common peroneal nerve injury. The extension of the injury to involve the interosseus membrane up to the distal tibiofibular joint. The association of popliteal artery injury is not reported before to the best of our knowledge. PMID:23162155

  7. Goal-Proximity Decision-Making

    ERIC Educational Resources Information Center

    Veksler, Vladislav D.; Gray, Wayne D.; Schoelles, Michael J.

    2013-01-01

    Reinforcement learning (RL) models of decision-making cannot account for human decisions in the absence of prior reward or punishment. We propose a mechanism for choosing among available options based on goal-option association strengths, where association strengths between objects represent previously experienced object proximity. The proposed…

  8. Vortices in normal part of proximity system

    DOE PAGESBeta

    Kogan, V. G.

    2015-05-26

    It is shown that the order parameter Δ induced in the normal part of superconductor-normal-superconductor proximity system is modulated in the magnetic field differently from vortices in bulk superconductors. Whereas Δ turns zero at vortex centers, the magnetic structure of these vortices differs from that of Abrikosov's.

  9. Email Keypals in Zone of Proximal Development.

    ERIC Educational Resources Information Center

    Kaufman, Lionel M., Jr.

    This study analyzed the discourse of electronic mail (e-mail) exchanges between students of English as a second language (ESL) and other ESL learners from other cultures and at varying proficiency levels (keypals), focusing on what these exchanges may reveal about learners' progress through the "Zone of Proximal Development," a Vygotskian concept…

  10. The Zone of Proximal "Teacher" Development

    ERIC Educational Resources Information Center

    Warford, Mark K.

    2011-01-01

    Toward the end of his short life, Lev Vygotsky found himself teaching teachers in a remote part of the USSR. Though his influence as a developmental psychologist is well-established, little is known about his approach to teacher development. This article applies the researcher's core concept, the zone of proximal development to teacher education.…

  11. Proximal humerus fractures in children and adolescents.

    PubMed

    Lefèvre, Y; Journeau, P; Angelliaume, A; Bouty, A; Dobremez, E

    2014-02-01

    Proximal humerus fractures are rare in paediatric traumatology. Metaphyseal fractures account for about 70% of cases and epiphyseal separation for the remaining 30%. The development and anatomy of the proximal humerus explain the various fracture types, displacements, and potential complications; and also help in interpreting the radiographic findings, most notably in young children. Physicians should be alert to the possibility of an underlying lesion or pathological fracture requiring appropriate diagnostic investigations, and they should consider child abuse in very young paediatric patients. Although the management of proximal humerus fractures remains controversial, the extraordinary remodelling potential of the proximal humerus in skeletally immature patients often allows non-operative treatment without prior reduction. When the displacement exceeds the remodelling potential suggested by the extent of impaction, angulation, and patient age, retrograde elastic stable intramedullary nailing (ESIN) provides effective stabilisation. As a result, the thoraco-brachial abduction cast is less often used, although this method remains a valid option. Retrograde ESIN must be performed by a surgeon who is thoroughly conversant with the fundamental underlying principles. Direct percutaneous pinning is a fall-back option when the surgeon's experience with ESIN is insufficient. Finally, open reduction is very rarely required and should be reserved for severely displaced fractures after failure of closed reduction. When these indications are followed, long-term outcomes are usually excellent, with prompt resumption of previous activities and a low rate of residual abnormalities. PMID:24394917

  12. Capacitive Proximity Sensors With Additional Driven Shields

    NASA Technical Reports Server (NTRS)

    Mcconnell, Robert L.

    1993-01-01

    Improved capacitive proximity sensors constructed by incorporating one or more additional driven shield(s). Sensitivity and range of sensor altered by adjusting driving signal(s) applied to shield(s). Includes sensing electrode and driven isolating shield that correspond to sensing electrode and driven shield.

  13. Characteristics of He II Proximity Profiles

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Syphers, David; Meiksin, Avery; Kriss, Gerard A.; Schneider, Donald P.; York, Donald G.; Anderson, Scott F.

    2015-06-01

    The proximity profile in the spectra of z≈ 3 quasars, where fluxes extend blueward of the He ii Lyα wavelength 304 (1+z) Å, is one of the most important spectral features in the study of the intergalactic medium (IGM). Based on the Hubble Space Telescope spectra of 24 He ii quasars, we find that the majority of them display a proximity profile, corresponding to an ionization radius as large as 20 Mpc in the source's rest frame. In comparison with those in the H i spectra of the quasars at z ≈ 6, the He ii proximity effect is more prominent and is observed over a considerably longer period of reionization. The He ii proximity zone sizes decrease at higher redshifts, particularly at z\\gt 3.3. This trend is similar to that for H i, signaling an onset of He ii reionization at z≳ 4. For quasar SDSS1253+6817 (z = 3.48), the He ii absorption trough displays a gradual decline and serves as a good case for modeling the He ii reionization. To model such a broad profile requires a quasar radiation field whose energy distribution between 4 and 1 Rydberg is considerably harder than normally assumed. The UV continuum of this quasar is indeed exceptionally steep, and the He ii ionization level in the quasar vicinity is higher than the average level in the IGM. These results are evidence that a very hard EUV continuum from this quasar produces a large ionized zone around it. Distinct exceptions are the two brightest He ii quasars at z ≈ 2.8, for which no significant proximity profile is present, probably implying that they are very young.

  14. Painful Spastic Hip Dislocation: Proximal Femoral Resection

    PubMed Central

    Albiñana, Javier; Gonzalez-Moran, Gaspar

    2002-01-01

    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despite routine post-operative skeletal traction in all cases and careful soft tissue interposition. One case showed significant heterotopic ossification which restricted prolonged sitting. This patient needed some occasional medication for pain. PMID:12180614

  15. Transverse Stress Fracture of the Proximal Patella

    PubMed Central

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-01-01

    Abstract Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete. A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity. Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID:26871789

  16. Isolated Proximal Tibiofibular Dislocation during Soccer

    PubMed Central

    Chiu, Casey; Sheele, Johnathan Michael

    2015-01-01

    Proximal tibiofibular dislocations are rarely encountered in the Emergency Department (ED). We present a case involving a man presenting to the ED with left knee pain after making a sharp left turn on the soccer field. His physical exam was only remarkable for tenderness over the lateral fibular head. His X-rays showed subtle abnormalities of the tibiofibular joint. The dislocation was reduced and the patient was discharged from the ED with orthopedic follow-up. PMID:26713164

  17. Large proximal ureteral stones: Ideal treatment modality?

    PubMed Central

    Kadyan, B.; Sabale, V.; Mane, D.; Satav, V.; Mulay, A.; Thakur, N.; Kankalia, S. P.

    2016-01-01

    Background and Purpose: Ideal treatment modality for patients with large impacted proximal ureteral stone remains controversial. We compared laparoscopic transperitoneal ureterolithotomy (Lap-TPUL) and semirigid ureteroscopy for large proximal ureteric stones to evaluate their efficacy and safety. Patients and Methods: From November 2012 to December 2014, we enrolled 122 patients with large (≥1.5 cm) proximal ureteral stone in the study. Patients were randomly divided into two groups: Group A (60 patients), retrograde ureteroscopic lithotripsy using a semirigid ureteroscope; Group B (62 patients), transperitoneal LU (Lap-TPUL). Results: The overall stone-free rate was 71.6% and 93.5% for Group A and Group B respectively (P = 0.008). Auxiliary procedure rate was higher in Group A than in Group B (27.3% vs. 5.6%). The complication rate was 11.2% in Group B versus 25% in Group A. Mean procedure time was higher in laparoscopy group as compared to ureterorenoscopy (URS) groups (84.07 ± 16.80 vs. 62.82 ± 12.71 min). Hospital stay was 4.16 ± 0.67 days in laparoscopy group and 1.18 ± 0.38 days in URS group (P < 0.0001). Conclusion: Laparoscopic transperitoneal ureterolithotomy is a minimally invasive, safe and effective treatment modality and should be recommended to all patients of impacted large proximal stones, which are not amenable to URS or extracorporeal shock-wave lithotripsy or as a primary modality of choice especially if patient is otherwise candidate for open surgery. PMID:27141190

  18. Proximal Sciatic Nerve Intraneural Ganglion Cyst

    PubMed Central

    Swartz, Karin R.; Wilson, Dianne; Boland, Michael; Fee, Dominic B.

    2009-01-01

    Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009. PMID:20069041

  19. Human proximal tubule cells form functional microtissues.

    PubMed

    Prange, Jenny A; Bieri, Manuela; Segerer, Stephan; Burger, Charlotte; Kaech, Andres; Moritz, Wolfgang; Devuyst, Olivier

    2016-04-01

    The epithelial cells lining the proximal tubules of the kidney mediate complex transport processes and are particularly vulnerable to drug toxicity. Drug toxicity studies are classically based on two-dimensional cultures of immortalized proximal tubular cells. Such immortalized cells are dedifferentiated, and lose transport properties (including saturable endocytic uptake) encountered in vivo. Generating differentiated, organotypic human microtissues would potentially alleviate these limitations and facilitate drug toxicity studies. Here, we describe the generation and characterization of kidney microtissues from immortalized (HK-2) and primary (HRPTEpiC) human renal proximal tubular epithelial cells under well-defined conditions. Microtissue cultures were done in hanging drop GravityPLUS™ culture plates and were characterized for morphology, proliferation and differentiation markers, and by monitoring the endocytic uptake of albumin. Kidney microtissues were successfully obtained by co-culturing HK-2 or HRPTEpiC cells with fibroblasts. The HK-2 microtissues formed highly proliferative, but dedifferentiated microtissues within 10 days of culture, while co-culture with fibroblasts yielded spherical structures already after 2 days. Low passage HRPTEpiC microtissues (mono- and co-culture) were less proliferative and expressed tissue-specific differentiation markers. Electron microscopy evidenced epithelial differentiation markers including microvilli, tight junctions, endosomes, and lysosomes in the co-cultured HRPTEpiC microtissues. The co-cultured HRPTEpiC microtissues showed specific uptake of albumin that could be inhibited by cadmium and gentamycin. In conclusion, we established a reliable hanging drop protocol to obtain functional kidney microtissues with proximal tubular epithelial cell lines. These microtissues could be used for high-throughput drug and toxicology screenings, with endocytosis as a functional readout. PMID:26676951

  20. Proximal tibial fracture following total knee arthroplasty.

    PubMed

    Krause, Heike; Dunleavy, Kim

    2011-09-01

    The patient was a 74-year-old man, with a history of total knee arthoplasty 14 years earlier, after having sustained a pathological fracture of the proximal diaphysis of the left tibia following a fall. Given the unstable nature of the fracture and the severe osteolysis noted below the total knee arthroplasty, surgical management 1 day after the fall entailed packing cancellous bone graft into the defect and realigning the fracture. PMID:21885911

  1. Capacitive Proximity Sensor Has Longer Range

    NASA Technical Reports Server (NTRS)

    Vranish, John M.

    1992-01-01

    Capacitive proximity sensor on robot arm detects nearby object via capacitive effect of object on frequency of oscillator. Sensing element part of oscillator circuit operating at about 20 kHz. Total capacitance between sensing element and ground constitutes tuning capacitance of oscillator. Sensor circuit includes shield driven by replica of alternating voltage applied to sensing element. Driven shield concentrates sensing electrostatic field in exterior region to enhance sensitivity to object. Sensitivity and dynamic range has corresponding 12-to-1 improvement.

  2. Proximity induced supercurrent in multilayer graphene

    NASA Astrophysics Data System (ADS)

    Kanda, Akinobu; Goto, Hidenori; Tanaka, Sho; Nagai, Yukitoshi; Ootuka, Youiti; Odaka, Shunsuke; Miyazaki, Hisao; Tsukagoshi, Kazuhito

    2009-03-01

    We report experimental study on gate-dependent superconducting proximity effect in multilayer graphene. In our sample, multilayer graphene (MLG), obtained by the micromechanical cleavage of Kish graphite, is placed on a SiO2/p^+-Si substrate, and two superconducting (Ti/Al) electrodes are connected to the top of the MLG. Dependence of the critical supercurrent on MLG length and temperature will be discussed.

  3. Gene teams with relaxed proximity constraint.

    PubMed

    Kim, Sun; Choi, Jeong-Hyeon; Yang, Jiong

    2005-01-01

    Functionally related genes co-evolve, probably due to the strong selection pressure in evolution. Thus we expect that they are present in multiple genomes. Physical proximity among genes, known as gene team, is a very useful concept to discover functionally related genes in multiple genomes. However, there are also many gene sets that do not preserve physical proximity. In this paper, we generalized the gene team model, that looks for gene clusters in a physically clustered form, to multiple genome cases with relaxed constraint. We propose a novel hybrid pattern model that combines the set and the sequential pattern models. Our model searches for gene clusters with and/or without physical proximity constraint. This model is implemented and tested with 97 genomes (120 replicons). The result was analyzed to show the usefulness of our model. Especially, analysis of gene clusters that belong to B. subtilis and E. coli demonstrated that our model predicted many experimentally verified operons and functionally related clusters. Our program is fast enough to provide a sevice on the web at http://platcom. informatics.indiana.edu/platcom/. Users can select any combination of 97 genomes to predict gene teams. PMID:16447961

  4. Trajectories in Close Proximity to Asteroids

    NASA Technical Reports Server (NTRS)

    Scheeres, D. J.

    2000-01-01

    Spacecraft motion in close proximity to irregularly shaped, rotating bodies such as asteroids presents a unique dynamical environment as compared to most space missions. There are several fundamental novelties in this environment that spacecraft must deal with. These include the possibility of orbital instabilities that can act over very short time spans (on the order of hours for some systems), possible non-uniform rotation of the central gravity field, divergence of traditional gravity field representations when close to the asteroid surface, dominance of perturbing forces, an extremely large asteroid model parameter space that must be prepared for in the absence of reliable information, and the possibility of employing new and novel trajectory control techniques such as hovering and repeated landings on the asteroid surface. An overview of how these novelties impact the space of feasible close proximity operations and how different asteroid model properties will affect their implementation is given. In so doing, four fundamental types of close proximity operations will be defined. Listed in order of increasing technical difficulty these are: (1) close, stable orbits; (2) low-altitude flyovers; (3) landing trajectories; and (4) hovering trajectories. The feasibility and difficulty of implementing these operations will vary as a function of the asteroid shape, size, density, and rotation properties, and as a function of the spacecraft navigation capability. Additional information is contained in the original extended abstract.

  5. Management of proximal humerus fractures in adults.

    PubMed

    Vachtsevanos, Leonidas; Hayden, Lydia; Desai, Aravind S; Dramis, Asterios

    2014-11-18

    The majority of proximal humerus fractures are low-energy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. The diversity of fracture patterns encountered renders objective classification of prognostic value challenging. Non-operative management has been associated with good functional outcomes in stable, minimally displaced and certain types of displaced fractures. Absolute indications for surgery are infrequent and comprise compound, pathological, multi-fragmentary head-splitting fractures and fracture dislocations, as well as those associated with neurovascular injury. A constantly expanding range of reconstructive and replacement options however has been extending the indications for surgical management of complex proximal humerus fractures. As a result, management decisions are becoming increasingly complicated, in an attempt to provide the best possible treatment for each individual patient, that will successfully address their specific fracture configuration, comorbidities and functional expectations. Our aim was to review the management options available for the full range of proximal humerus fractures in adults, along with their specific advantages, disadvantages and outcomes. PMID:25405098

  6. Salicylate-induced proximal tubular dysfunction.

    PubMed

    Tsimihodimos, Vasilis; Psychogios, Nikolaos; Kakaidi, Varvara; Bairaktari, Eleni; Elisaf, Moses

    2007-09-01

    We describe the case of a 17-year-old girl who was admitted to our clinic for drug poisoning. Twelve hours after the ingestion of 25 tablets of aspirin (12.5 g of acetylsalicylic acid), the patient had a generalized proximal tubular dysfunction characterized by glucosuria (in the face of normal serum glucose levels), proteinuria, and uric acid wasting. Further characterization of the tubular dysfunction using high-resolution proton nuclear magnetic resonance spectroscopy of the urine showed a pattern consistent with proximal tubular injury. An important characteristic of the salicylate-induced proximal tubular dysfunction in our patient was its rapid reversibility. A trend toward normalization of fractional excretion values of electrolytes was observed 2 days after ingestion. Determination of serum and urine metabolites and spectroscopy of urine 15 days later showed no evidence of tubular dysfunction. The mechanisms potentially implicated in the pathogenesis of salicylate-induced Fanconi syndrome are discussed and a brief review of the relevant literature is provided. PMID:17720526

  7. Links between soil modelling and proximal sensing

    NASA Astrophysics Data System (ADS)

    Aitkenhead, Matt; McBratney, Alex; Minasny, Budiman

    2015-04-01

    Proximal sensing of soils can provide valuable information for soil modelling, by providing baseline data and validating model predictions through direct observation of soil characteristics. A wide range of soil parameters can be estimated using proximal sensing of soils (PSS), often simultaneously using single hand-held systems, of which there are many types. The benefits for soil modelling include direct observation of modelled parameters, rapid assessment in field conditions and digital data acquisition, making the transfer of information to soil models relatively straightforward. This is an active area of development, with research into improved methods of field-based capture of soil parameters directly relevant for soil modelling. A number of challenges exist, including the removal of or accounting for the effects of field conditions (e.g. soil moisture and structure), and the development of libraries of data that will allow calibration models to be produced. We present an overview of PSS as it relates to soil modelling, including equipment types, calibration approaches, cloud-based processing, soil parameters and processes estimated using PSS, and opportunities and challenges for the future. We also identify and discuss the possibilities for integration of modelling and proximal sensing within precision agriculture/precision land management.

  8. Proximity sensing with wavelet generated video

    NASA Astrophysics Data System (ADS)

    Noel, Steven E.; Szu, Harold H.

    1998-10-01

    In this paper we introduce wavelet video processing of proximity sensor signals. Proximity sensing is required for a wide range of military and commercial applications, including weapon fuzzing, robotics, and automotive collision avoidance. While our proposed method temporarily increases signal dimension, it eventually performs data compression through the extraction of salient signal features. This data compression in turn reduces the necessary complexity of the remaining computational processing. We demonstrate our method of wavelet video processing via the proximity sensing of nearby objects through their Doppler shift. In doing this we perform a continuous wavelet transform on the Doppler signal, after subjecting it to a time-varying window. We then extract signal features from the resulting wavelet video, which we use as input to pattern recognition neural networks. The networks are trained to estimate the time- varying Doppler shift from the extracted features. We test the estimation performance of the networks, using different degrees of nonlinearity in the frequency shift over time and different levels of noise. We give the analytical result that the signal-to-noise enhancement of our proposed method is at least as good as the square root of the number of video frames, although more work is needed to completely quantify this. Real-time wavelet-based video processing and compression technology recently developed under the DOD WAVENET program offers an exciting opportunity to more fully investigate our proposed method.

  9. Autophagy Induces Prosenescent Changes in Proximal Tubular S3 Segments.

    PubMed

    Baisantry, Arpita; Bhayana, Sagar; Rong, Song; Ermeling, Esther; Wrede, Christoph; Hegermann, Jan; Pennekamp, Petra; Sörensen-Zender, Inga; Haller, Hermann; Melk, Anette; Schmitt, Roland

    2016-06-01

    Evidence suggests that autophagy promotes the development of cellular senescence. Because cellular senescence contributes to renal aging and promotes the progression from AKI to CKD, we investigated the potential effect of tubular autophagy on senescence induction. Compared with kidneys from control mice, kidneys from mice with conditional deletion of autophagy-related 5 (Atg5) for selective ablation of autophagy in proximal tubular S3 segments (Atg5(Δ) (flox/) (Δ) (flox)) presented with significantly less tubular senescence, reduced interstitial fibrosis, and superior renal function 30 days after ischemia/reperfusion injury. To correlate this long-term outcome with differences in the early injury process, kidneys were analyzed 2 hours and 3 days after reperfusion. Notably, compared with kidneys of control mice, Atg5(Δ) (flox/) (Δ) (flox) kidneys showed more cell death in outer medullary S3 segments at 2 hours but less tubular damage and inflammation at day 3. These data suggest that the lack of autophagy prevents early survival mechanisms in severely damaged tubular cells. However, if such compromised cells persist, then they may lead to maladaptive repair and proinflammatory changes, thereby facilitating the development of a senescent phenotype and CKD. PMID:26487561

  10. 14 CFR 135.153 - Ground proximity warning system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Ground proximity warning system. 135.153... Equipment § 135.153 Ground proximity warning system. (a) No person may operate a turbine-powered airplane... equipped with an approved ground proximity warning system. (b) (c) For a system required by this...

  11. 14 CFR 135.153 - Ground proximity warning system.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Ground proximity warning system. 135.153... Equipment § 135.153 Ground proximity warning system. (a) No person may operate a turbine-powered airplane... equipped with an approved ground proximity warning system. (b) (c) For a system required by this...

  12. Hand Replantation with Proximal Row Carpectomy

    PubMed Central

    Lee, Young-Keun; Lee, Hang-Ho; Park, Ji-Kang; Kim, Joo-Yong; Dhawan, Vikas

    2008-01-01

    The purpose of this study is to present our operative technique and postoperative results of the hand replantation with proximal row carpectomy in cases of complete amputation at the level of wrist joint. From May 2003 to April 2005, five patients suffered from complete amputation of the hand due to industrial trauma. Amputation level was radiocarpal joint in three cases and midcarpal joint in two cases. Three cases represented guillotine type and two cases with local crush type injuries. All were men and the mean age was 26.6 years. The mean follow-up period was 26.8 months. At the time of replantation, the wrist joint was stabilized with transarticular fixation using three to four Kirschner’s wires after performing proximal row carpectomy. Postoperatively, functional results such as muscle strength, range of motion of the wrist and fingers, and sensory recovery were assessed according to Chen’s criteria. Joint width and arthritic changes of the radio-capitate joint were evaluated with radiologic tools. According to Chen’s criteria, the overall results in five cases were classified as grade II. Intrinsic muscle power of hands was found to be grade 4. The mean grip and pinch powers were 41% and 45%, respectively, compared to contralateral hand. The mean arc of flexion–extension of wrist was 53°. Total mean active motion of fingers was 215 degrees. Static two-point discrimination of fingertip ranged from 8 to 13 mm. On the follow-up, computerized tomography showed well-preserved radio-capitate joint space without any arthritic changes. While performing hand replantation after amputation at the radiocarpal or midcarpal level, proximal row carpectomy is a useful procedure to preserve joint motion of the wrist in selected cases. PMID:18855073

  13. Scintillation proximity assay using polymeric membranes

    SciTech Connect

    Mansfield, R.K.

    1992-01-01

    Liquid scintillation counting (LSC) is typically used to quantify electron emitting isotopes. In LSC, radioactive samples are dissolved in an organic fluor solution (scintillation cocktail) to ensure that the label is close enough to the fluor molecules to be detected. Although efficient, scintillation cocktail is neither specific or selective for samples labeled with the same radioisotope. Scintillation cocktail is flammable posing significant health risks to the user and is expensive to purchase and discard. Scintillation Proximity Assay (SPA) is a radioanalytical technique where only those radiochemical entities (RCE's) bound to fluor containing matrices are detected. Only bound RCE's are in close enough proximity the entrapped fluor molecules to induce scintillations. Unbound radioligands are too far removed from the fluor molecules to be detected. The research in this dissertation focused on the development and evaluation of fluor-containing membranes (scintillation proximity membranes, SP membranes) to be used for specific radioanalytical techniques without using scintillation cocktail. Polysulfone and PVC SP membranes prepared in our laboratory were investigated for radioimmunossay (RIA) where only bound radioligand is detected, thereby eliminating the separation step impeding the automation of RIA. These SP membranes performed RIA where the results were nearly identical to commercial SP microbeads. SP membranes functionalized with quaternary ammonium hydroxide moieties were able to trap and quantify [sup 14]CO[sub 2] without using liquid scintillation cocktail. RCE's bound in the pore structure of SP membranes are intimate with the entrapped fluor providing the geometry needed for high detection efficiencies. Absorbent SP membranes were used in radiation surveys and were shown to be as effective as conventional survey techniques using filter paper and scintillation cocktail.

  14. Delayed homicides and the proximate cause.

    PubMed

    Lin, Peter; Gill, James R

    2009-12-01

    Delayed homicides result from complications of remote injuries inflicted by "the hands of another." The investigation of delayed homicides may be a challenge due to a number of factors including: failure to report the death to the proper authorities, lack of ready and adequate documentation of the original injury and circumstances, and jurisdictional differences between the places of injury and death. The certification of these deaths also requires the demonstration of a pathophysiologic link between the remote injury and death. In sorting through these issues, it is helpful to rely upon the definition of the proximate cause of death. Over a 2-year period in New York City, there were 1211 deaths certified as homicide of which 42 were due to injuries sustained greater than 1 year before death. The survival interval ranged from 1.3 to 43.2 years. The most common immediate causes of death were: infections (22), seizures (7), and intestinal obstructions/hernias (6). Common patterns of complications included infection following a gunshot wound of the spinal cord, seizure disorder due to blunt head trauma, and intestinal obstruction/hernia due to adhesions from an abdominal stab wound. Spinal cord injuries resulted in paraplegia in 14 instances and quadriplegia in 8. The mean survival interval for paraplegics was 20.3 years and 14.8 years for quadriplegics; infections were a frequent immediate cause of death in both groups, particularly infections due to chronic bladder catheterization. The definition of proximate cause originated with civil law cases and was later applied to death certification as the proximate cause of death. The gradual extinction of the "year and a day rule" for the limitation of bringing homicide charges in delayed deaths may result in more of these deaths going to trial. Medical examiners/coroners must be able to explain the reasoning behind these death certifications and maintain consistent standards for the certification of all delayed deaths due

  15. Bicarbonate secretion by rabbit proximal colon.

    PubMed

    Sullivan, S K; Smith, P L

    1986-10-01

    Stripped segments of proximal colon (1-6 cm distal to the ampulla caecalis coli) were studied in vitro in Ussing chambers under short-circuit conditions using the pH-stat technique. With glucose and HCO3-CO2 present in the serosal bathing solution only, proximal colon alkalinizes the luminal bathing solution at a rate of 2.1 +/- 0.2 mu eq X h-1 X cm-2 (n = 36). With HCO3-CO2 present in the luminal bathing solution alone, proximal colon does not significantly acidify or alkalinize the serosal bathing solution. Addition of glucose (10 mM) to the luminal bathing solution abolished luminal alkalinization. Removal of HCO3 and CO2 from the serosal bathing solution or replacement of O2 with N2 also abolished luminal alkalinization. Acetazolamide (0.1 mM) added to both bathing solutions did not alter the rate of luminal alkalinization. Ion-replacement studies revealed that the alkalinization process was highly dependent on the presence of Na in the bathing solutions and much less dependent on the presence of Cl. Furthermore, ouabain (0.1 mM) significantly reduced luminal alkalinization. As in rabbit ileum, serosal epinephrine (0.1 mM) did not alter luminal alkalinization but increased serosal alkalinization by a Na-dependent mechanism. These results suggest that luminal alkalinization results from a Na-dependent, active transcellular HCO3 transport process and that a Na-dependent HCO3 absorptive process is activated by adrenergic stimuli. PMID:3766731

  16. Space station proximity operations and window design

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    On-orbit proximity operations (PROX-OPS) consist of all extravehicular activity (EVA) within 1 km of the space station. Because of the potentially large variety of PROX-OPS, very careful planning for space station windows is called for and must consider a great many human factors. The following topics are discussed: (1) basic window design philosophy and assumptions; (2) the concept of the local horizontal - local vertical on-orbit; (3) window linear dimensions; (4) selected anthropomorphic considerations; (5) displays and controls relative to windows; and (6) full window assembly replacement.

  17. Unilateral Isolated Proximal Femoral Focal Deficiency

    PubMed Central

    Doğer, Emek; Köpük, Şule Y.; Çakıroğlu, Yiğit; Çakır, Özgür; Yücesoy, Gülseren

    2013-01-01

    Objective. To discuss a patient with a prenatal diagnosis of unilateral isolated femoral focal deficiency. Case. Antenatal diagnosis of unilateral isolated femoral focal deficiency was made at 20 weeks of gestation. The length of left femur was shorter than the right, and fetal femur length was below the fifth percentile. Proximal femoral focal deficiency was diagnosed. After delivery, the diagnosis was confirmed with skeletal radiographs and magnetic resonance imaging. In prenatal ultrasonographic examination, the early recognition and exclusion of skeletal dysplasias is important; moreover, treatment plans should be initiated, and valuable information should be provided to the family. PMID:23984135

  18. Metastatic disease of the proximal femur.

    PubMed

    Faisham, W I; Zulmi, W; Biswal, B M

    2003-03-01

    Since January 1999, ten patients had undergone surgical treatment for metastatic bony lesions of proximal femur at this centre. Seven of these patients were treated for complete pathological fractures, one for impending fracture and one for revision of internal fixation and loosening of hemiarthroplasty. Primary malignancies were located in breast in four cases, prostate in three and one in lung, thyroid and neurofibrosarcoma. Two patients had died within six months after surgery, four after 1 year while the remaining four were still alive. The mean duration of survival was eleven months. Nine patients had been ambulating pain free and there were no failure of reconstruction. PMID:14556337

  19. Giant proximity effect in cuprate superconductors.

    PubMed

    Bozovic, I; Logvenov, G; Verhoeven, M A J; Caputo, P; Goldobin, E; Beasley, M R

    2004-10-01

    Using an advanced molecular beam epitaxy system, we have reproducibly synthesized atomically smooth films of high-temperature superconductors and uniform trilayer junctions with virtually perfect interfaces. We found that supercurrent runs through very thick barriers. We can rule out pinholes and microshorts; this "giant proximity effect" (GPE) is intrinsic. It defies the conventional explanation; it might originate in resonant tunneling through pair states in an almost-superconducting barrier. GPE may also be significant for superconducting electronics, since thick barriers are easier to fabricate. PMID:15524925

  20. Impacted valgus fractures of the proximal humerus.

    PubMed

    Ribeiro, Fabiano Rebouças; Takesian, Fernando Hovaguim; Bezerra, Luiz Eduardo Pimentel; Filho, Rômulo Brasil; Júnior, Antonio Carlos Tenor; da Costa, Miguel Pereira

    2016-01-01

    Impacted valgus fractures of the proximal humerus are considered to be a special type fracture, since impaction of the humeral head on the metaphysis with maintenance of the posteromedial periosteum improves the prognosis regarding occurrences of avascular necrosis. This characteristic can also facilitate the reduction maneuver and increase the consolidation rate of these fractures, even in more complex cases. The studies included were obtained by searching the Bireme, Medline, PubMed, Cochrane Library and Google Scholar databases for those published between 1991 and 2013. The objective of this study was to identify the most common definitions, classifications and treatment methods used for these fractures in the orthopedic medical literature. PMID:27069878

  1. An automated system for spacecraft proximity operations

    NASA Technical Reports Server (NTRS)

    Bergmann, E.

    1991-01-01

    With the advent of multiple-vehicle operations in support of the space station, on-orbit refurbishment, and several other missions, there is a need to intelligently plan proximity operations trajectories that will conserve limited available fuel while avoiding collisions. Upon reaching the objective, the capture process entails several unique considerations, such as coordinating motion with a tumbling target, the capture itself, and adapting to control of the new configuration resulting from the capture operation. This paper outlines a systematic process of technical development over several years at the Draper laboratory, culminating in a capability to perform manual augmented or fully autonomous rendezvous, capture, and control of the resulting configuration.

  2. Ganglions of the proximal interphalangeal joint.

    PubMed

    Cheng, C A; Rockwell, W B

    1999-08-01

    Ganglion cysts-the most common hand tumors-usually affect women in their twenties and thirties. The cause of these cysts is unknown, although trauma has been postulated as an inciting factor. Ganglions occur most commonly at the dorsal and palmar wrist. However, ganglions of the proximal interphalangeal (PIP) joint are rare. Four patients with PIP joint ganglions were recently treated at our institution. Three received aspiration and one received operative therapy, all with good results. All four patients were older than 65 years. PMID:10470671

  3. Impacted valgus fractures of the proximal humerus☆

    PubMed Central

    Ribeiro, Fabiano Rebouças; Takesian, Fernando Hovaguim; Bezerra, Luiz Eduardo Pimentel; Filho, Rômulo Brasil; Júnior, Antonio Carlos Tenor; da Costa, Miguel Pereira

    2016-01-01

    Impacted valgus fractures of the proximal humerus are considered to be a special type fracture, since impaction of the humeral head on the metaphysis with maintenance of the posteromedial periosteum improves the prognosis regarding occurrences of avascular necrosis. This characteristic can also facilitate the reduction maneuver and increase the consolidation rate of these fractures, even in more complex cases. The studies included were obtained by searching the Bireme, Medline, PubMed, Cochrane Library and Google Scholar databases for those published between 1991 and 2013. The objective of this study was to identify the most common definitions, classifications and treatment methods used for these fractures in the orthopedic medical literature. PMID:27069878

  4. Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.

    PubMed

    Li, Xiao C; Zhuo, Jia L

    2016-08-01

    It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na(+) reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension. Careful analysis of available evidence supports the hypothesis that both local synthesis or formation and AT1 (AT1a) receptor- and/or megalin-mediated uptake of angiotensinogen (AGT), ANG I and ANG II contribute to high levels of ANG II in the proximal tubules of the kidney. Under physiological conditions, nearly all major components of the RAS including AGT, prorenin, renin, ANG I, and ANG II would be filtered by the glomerulus and taken up by the proximal tubules. In ANG II-dependent hypertension, the expression of AGT, prorenin, and (pro)renin receptors, and angiotensin-converting enzyme (ACE) is upregulated rather than downregulated in the kidney. Furthermore, hypertension damages the glomerular filtration barrier, which augments the filtration of circulating AGT, prorenin, renin, ANG I, and ANG II and their uptake in the proximal tubules. Together, increased local ANG II formation and augmented uptake of circulating ANG II in the proximal tubules, via activation of AT1 (AT1a) receptors and Na(+)/H(+) exchanger 3, may provide a powerful feedforward mechanism for promoting Na(+) retention and the development of ANG II-induced hypertension. PMID:27372447

  5. True Aneurysm of the Proximal Brachial Artery

    PubMed Central

    Ramakrishna, Pinjala; Mahapatra, Sandeep; Rajesh, Ratna

    2013-01-01

    A 35-year-old farmer presented with complaints of pain in the right upper limb for 1 month and bluish discoloration of the right-hand finger tips with tingling and numbness. He sustained injury to the right upper limb while lifting a heavy object 1 mo previously. There was an ovoid swelling of 4 × 2 cm on the medial aspect of the right arm, 12 cm above the medial epicondyle at the level of the armpit with visible pulsations. There was distal neurovascular deficit. Duplex scan of the right upper limb arterial system revealed a pseudoaneurysm of the proximal right brachial artery, with dampened monophasic flow in the ulnar artery and no flow in the radial artery. Spiral computed tomography angiogram showed the presence of an echogenic periarterial lesion in the proximal brachial artery suggestive of pseudoaneurysm or an extrinsic compression by hematoma. Distal brachial artery was found to have filled with thrombus, with non-opacification of the radial and the distal ulnar artery. The patient was posted for excision of the aneurysmal arterial segment. A 5-cm-long reversed segment of vein graft was interposed in between the cut ends of the brachial artery. Histopathology: Specimen shows a part of the vessel wall composed of intimal, medial, and adventitial layers with intraluminal thrombus showing evidence of recanalization suggestive of true aneurysm of the brachial artery. PMID:26798692

  6. Rheogenic transport in the renal proximal tubule

    PubMed Central

    1983-01-01

    The electrophysiology of the renal Na-K ATPase was studied in isolated perfused amphibian proximal tubules during alterations in bath (serosal) potassium. Intracellular and extracellular ionic activity measurements permitted continuous evaluation of the Nernst potentials for Na+, K+, and Cl- across the basolateral membrane. The cell membrane and transepithelial potential differences and resistances were also determined. Return of K to the basal (serosal) solution after a 20-min incubation in K-free solution hyperpolarized the basolateral membrane to an electrical potential that was more negative than the Nernst potential for either Na, Cl, or K. This constitutes strong evidence that at least under stimulated conditions the Na-K ATPase located at the basolateral membrane of the renal proximal tubule mediates a rheogenic process which directly transfers net charge across the cell membrane. Interpretation of these data in terms of an electrical equivalent circuit permitted calculation of both the rheogenic current and the Na/K coupling ratio of the basolateral pump. During the period between 1 and 3 min after pump reactivation by return of bath K, the basolateral rheogenic current was directly proportional to the intracellular Na activity, and the pump stoichiometry transiently exceeded the coupling ratio of 3Na to 2K reported in other preparations. PMID:6319539

  7. Demonstration of automated proximity and docking technology

    NASA Technical Reports Server (NTRS)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.

    1991-01-01

    Automated spacecraft docking operations are being performed using a full scale motion based simulator and an optical sensor. This presentation will discuss the work in progress at TRW and MSFC facilities to study the problem of automated proximity and docking operations. The docking sensor used in the MSFC Optical Sensor and simulation runs are performed using the MSFC Flat Floor Facility. The control algorithms and six degrees of freedom (6DOF) simulation software were developed at TRW and integrated into the MSFC facility. Key issues being studied are the quantification of docking sensor requirements and operational constraints necessary to perform automated docking maneuvers, control algorithms capable of performing automated docking in the presence of sensitive and noisy sensor data, and sensor technologies for automated proximity and docking operations. As part of this study the MSFC sensor characteristics were analyzed and modeled so that off line simulation runs can be performed for control algorithm testing. Our goal is to develop and demonstrate full 6DOF docking capabilities with actual sensors on the MSFC motion based simulator. We present findings from actual docking simulation runs which show sensor and control loop performance as well as problem areas which require close attention. The evolution of various control algorithms using both phase plane and Clohessy-Wiltshire techniques are discussed. In addition, 6DOF target acquisition and control strategies are described.

  8. An improved proximity force approximation for electrostatics

    SciTech Connect

    Fosco, Cesar D.; Lombardo, Fernando C.; Mazzitelli, Francisco D.

    2012-08-15

    A quite straightforward approximation for the electrostatic interaction between two perfectly conducting surfaces suggests itself when the distance between them is much smaller than the characteristic lengths associated with their shapes. Indeed, in the so called 'proximity force approximation' the electrostatic force is evaluated by first dividing each surface into a set of small flat patches, and then adding up the forces due two opposite pairs, the contributions of which are approximated as due to pairs of parallel planes. This approximation has been widely and successfully applied in different contexts, ranging from nuclear physics to Casimir effect calculations. We present here an improvement on this approximation, based on a derivative expansion for the electrostatic energy contained between the surfaces. The results obtained could be useful for discussing the geometric dependence of the electrostatic force, and also as a convenient benchmark for numerical analyses of the tip-sample electrostatic interaction in atomic force microscopes. - Highlights: Black-Right-Pointing-Pointer The proximity force approximation (PFA) has been widely used in different areas. Black-Right-Pointing-Pointer The PFA can be improved using a derivative expansion in the shape of the surfaces. Black-Right-Pointing-Pointer We use the improved PFA to compute electrostatic forces between conductors. Black-Right-Pointing-Pointer The results can be used as an analytic benchmark for numerical calculations in AFM. Black-Right-Pointing-Pointer Insight is provided for people who use the PFA to compute nuclear and Casimir forces.

  9. Synostosis of the proximal tibiofibular joint.

    PubMed

    Sferopoulos, Nikolaos K

    2010-01-01

    The incidence of synostosis of the proximal tibiofibular joint (TFJ) was assessed among 1029 patients examined for osteoarthritis of the knee in a 4-year period. Radiographic evidence of a synostosis of the proximal TFJ was demonstrated in 3 knees (3 patients). The synostosis appeared incidental and was not the cause of symptoms in any of them. These patients were further examined with MRI and/or CT scans. In two cases, which were found to be primary (idiopathic), the synostosis was complete and bony. In a third case the lesion was secondary (acquired) to surgical reconstruction for a depressed fracture of the lateral tibial plateau. This iatrogenic complication followed open reduction, internal fixation, and grafting with synthetic bone. The bridging of the joint on the CT views was partial and compatible with ectopic calcification rather than ossification. The patients were treated conservatively and were followed for an average period of 3 years. No evidence that the synostosis accelerated the onset or progression of the degenerative changes to the ipsilateral knee could be verified. PMID:20592991

  10. Synostosis of the Proximal Tibiofibular Joint

    PubMed Central

    Sferopoulos, Nikolaos K.

    2010-01-01

    The incidence of synostosis of the proximal tibiofibular joint (TFJ) was assessed among 1029 patients examined for osteoarthritis of the knee in a 4-year period. Radiographic evidence of a synostosis of the proximal TFJ was demonstrated in 3 knees (3 patients). The synostosis appeared incidental and was not the cause of symptoms in any of them. These patients were further examined with MRI and/or CT scans. In two cases, which were found to be primary (idiopathic), the synostosis was complete and bony. In a third case the lesion was secondary (acquired) to surgical reconstruction for a depressed fracture of the lateral tibial plateau. This iatrogenic complication followed open reduction, internal fixation, and grafting with synthetic bone. The bridging of the joint on the CT views was partial and compatible with ectopic calcification rather than ossification. The patients were treated conservatively and were followed for an average period of 3 years. No evidence that the synostosis accelerated the onset or progression of the degenerative changes to the ipsilateral knee could be verified. PMID:20592991

  11. Proximate determinants of fertility in peninsular Malaysia.

    PubMed

    Tey, Nai Peng; Ng, Sor Tho; Yew, Siew Yong

    2012-05-01

    The continuing decline in fertility despite a contraction in contraceptive use in Peninsular Malaysia since the mid-1980s has triggered considerable interest in the reasons behind this phenomenon, such as increase in abortion, sterility, and out-of-wedlock pregnancy. Fertility decline has been attributed to rapid socioeconomic development, which can only influence fertility through the intermediate variables. Application of vital statistics, population census, and survey data of Peninsular Malaysia on Bongaarts's model vindicates that marriage postponement and contraceptive use are the 2 most important proximate determinants of fertility, but the effects are not uniform across the ethnic groups. For instance, the predicted total fertility rate for Chinese and Malays are 2.9 and 1.6, respectively, compared with the observed level of 3.0 and 1.9. Postpartum infecundability and abortion also play a part in explaining ethnic fertility differentials. The fertility inhibiting effects of these proximate determinants have significant implications on reproductive health and future population growth. PMID:21490114

  12. Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis.

    PubMed

    Takaori, Koji; Nakamura, Jin; Yamamoto, Shinya; Nakata, Hirosuke; Sato, Yuki; Takase, Masayuki; Nameta, Masaaki; Yamamoto, Tadashi; Economides, Aris N; Kohno, Kenji; Haga, Hironori; Sharma, Kumar; Yanagita, Motoko

    2016-08-01

    AKI increases the risk of developing CKD, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers features of CKD. We generated a novel mouse model to induce proximal tubule-specific adjustable injury by inducing the expression of diphtheria toxin (DT) receptor with variable prevalence in proximal tubules. Administration of high-dose DT in mice expressing the DT receptor consistently caused severe proximal tubule-specific injury associated with interstitial fibrosis and reduction of erythropoietin production. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis, inflammation, glomerulosclerosis, and atubular glomeruli. DT-induced proximal tubule-specific injury also triggered distal tubule injury. Furthermore, injured tubular cells cocultured with fibroblasts stimulated induction of extracellular matrix and inflammatory genes. These results support the existence of proximal-distal tubule crosstalk and crosstalk between tubular cells and fibroblasts. Overall, our data provide evidence that proximal tubule injury triggers several features of CKD and that the severity and frequency of proximal tubule injury determines the progression to CKD. PMID:26701981

  13. Parallel Proximity Detection for Computer Simulations

    NASA Technical Reports Server (NTRS)

    Steinman, Jeffrey S. (Inventor); Wieland, Frederick P. (Inventor)

    1998-01-01

    The present invention discloses a system for performing proximity detection in computer simulations on parallel processing architectures utilizing a distribution list which includes movers and sensor coverages which check in and out of grids. Each mover maintains a list of sensors that detect the mover's motion as the mover and sensor coverages check in and out of the grids. Fuzzy grids are included by fuzzy resolution parameters to allow movers and sensor coverages to check in and out of grids without computing exact grid crossings. The movers check in and out of grids while moving sensors periodically inform the grids of their coverage. In addition, a lookahead function is also included for providing a generalized capability without making any limiting assumptions about the particular application to which it is applied. The lookahead function is initiated so that risk-free synchronization strategies never roll back grid events. The lookahead function adds fixed delays as events are scheduled for objects on other nodes.

  14. Optical detection of the superconducting proximity effect

    SciTech Connect

    Greene, L.H.; Abeyta, A.C.; Roshchin, I.V.; Robinson, I.K.; Dorsten, J.F.; Tanzer, T.A.; Bohn, P.W.

    1996-12-31

    The authors present the first detection of a superconducting proximity effect by optical techniques. Raman scattering on n{sup +}-InAs is performed through very thin, high-quality, superconducting Nb films grown directly on the (100) InAs surface. The 6 to 10 nm thick Nb films exhibit {Tc}`s of 2.5 to 5.5 K, as measured by electronic transport, and are flat to {approximately}0.5 nm, as measured by x-ray reflectivity. As the Nb/InAs structure is cooled below the superconducting transition temperature, the magnitude of the unscreened LO phonon mode, associated with the surface charge accumulation layer in the InAs, is observed to be enhanced by more than 40%. This reversible change is observed only when the Nb is in good electrical contact with the InAs.

  15. Parallel Proximity Detection for Computer Simulation

    NASA Technical Reports Server (NTRS)

    Steinman, Jeffrey S. (Inventor); Wieland, Frederick P. (Inventor)

    1997-01-01

    The present invention discloses a system for performing proximity detection in computer simulations on parallel processing architectures utilizing a distribution list which includes movers and sensor coverages which check in and out of grids. Each mover maintains a list of sensors that detect the mover's motion as the mover and sensor coverages check in and out of the grids. Fuzzy grids are includes by fuzzy resolution parameters to allow movers and sensor coverages to check in and out of grids without computing exact grid crossings. The movers check in and out of grids while moving sensors periodically inform the grids of their coverage. In addition, a lookahead function is also included for providing a generalized capability without making any limiting assumptions about the particular application to which it is applied. The lookahead function is initiated so that risk-free synchronization strategies never roll back grid events. The lookahead function adds fixed delays as events are scheduled for objects on other nodes.

  16. Protein structure alignment beyond spatial proximity

    PubMed Central

    Wang, Sheng; Ma, Jianzhu; Peng, Jian; Xu, Jinbo

    2013-01-01

    Protein structure alignment is a fundamental problem in computational structure biology. Many programs have been developed for automatic protein structure alignment, but most of them align two protein structures purely based upon geometric similarity without considering evolutionary and functional relationship. As such, these programs may generate structure alignments which are not very biologically meaningful from the evolutionary perspective. This paper presents a novel method DeepAlign for automatic pairwise protein structure alignment. DeepAlign aligns two protein structures using not only spatial proximity of equivalent residues (after rigid-body superposition), but also evolutionary relationship and hydrogen-bonding similarity. Experimental results show that DeepAlign can generate structure alignments much more consistent with manually-curated alignments than other automatic tools especially when proteins under consideration are remote homologs. These results imply that in addition to geometric similarity, evolutionary information and hydrogen-bonding similarity are essential to aligning two protein structures. PMID:23486213

  17. [Ophthalmologists in the proximity of Adolf Hitler].

    PubMed

    Rohrbach, J M

    2012-10-01

    Adolf Hitler met or at least knew about 5 ophthalmologists. The chair of ophthalmology in Berlin, Walther Löhlein, personally examined Hitler's eyes at least two times. The chair of ophthalmology in Breslau, Walter Dieter, developed "air raid protection spectacles" with the aid of high representatives of the NS-system and probably Adolf Hitler himself. Heinrich Wilhelm Kranz became rector of the universities of Giessen and Frankfurt/Main. He was known as a very strict advocate of the NS-race hygiene. Werner Zabel made plans for Hitler's diet and tried to interfere with Hitler's medical treatment. Finally, Hellmuth Unger was an influential representative of the medical press and a famous writer. Three of his novels with medical topics were made into a film which Hitler probably saw. Hitler had, so to say, a small "ophthalmological proximity" which, however, did not play a significant role for himself or the NS-state. PMID:22664943

  18. Vaccination Rates are Associated With Functional Proximity But Not Base Proximity of Vaccination Clinics

    PubMed Central

    Beshears, John; Choi, James J.; Laibson, David I.; Madrian, Brigitte C.

    2016-01-01

    Background: Routine annual influenza vaccinations are recommended for persons 6 months of age and older, but less than half of US adults get vaccinated. Many employers offer employees free influenza vaccinations at workplace clinics, but even then take-up is low. Objective: To determine whether employees are significantly more likely to get vaccinated if they have a higher probability of walking by the clinic for reasons other than vaccination. Method: We obtained data from an employer with a free workplace influenza vaccination clinic. Using each employee’s building entry/exit swipe card data, we test whether functional proximity—the likelihood that the employee walks by the clinic for reasons other than vaccination—predicts whether the employee gets vaccinated at the clinic. We also test whether base proximity—the inverse of walking distance from the employee’s desk to the clinic—predicts vaccination probability. Participants: A total of 1801 employees of a health benefits administrator that held a free workplace influenza vaccination clinic. Results: A 2 SD increase in functional proximity is associated with a 6.4 percentage point increase in the probability of vaccination (total vaccination rate at company=40%), even though the average employee’s desk is only 166 meters from the clinic. Base proximity does not predict vaccination probability. Conclusions and Relevance: Minor changes in the environment can have substantial effects on the probability of vaccination. If these results generalize, health systems should emphasize functional proximity over base proximity when locating preventive health services. PMID:27177295

  19. Proximity Operations and Docking Sensor Development

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Bryan, Thomas C.; Brewster, Linda L.; Lee, James E.

    2009-01-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) has been under development for the last three years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in spot mode out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. 12 Parts obsolescence issues prevent the construction of more AVGS units, and the next generation sensor was updated to allow it to support the CEV and COTS programs. The flight proven AR&D sensor has been redesigned to update parts and add additional capabilities for CEV and COTS with the development of the Next Generation AVGS at the Marshall Space Flight Center. The obsolete imager and processor are being replaced with new radiation tolerant parts. In addition, new capabilities include greater sensor range, auto ranging capability, and real-time video output. This paper presents some sensor hardware trades, use of highly integrated laser components, and addresses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements

  20. Proximal relationships between PTSD and drinking behavior.

    PubMed

    Kaysen, Debra; Stappenbeck, Cynthia; Rhew, Issac; Simpson, Tracy

    2014-01-01

    Co-morbid PTSD and alcohol use disorders are both common and debilitating. However, many of these studies rely on cross-sectional studies that obscure more complex relationships between PTSD and drinking. Event-level studies allow for examination of proximal relationships between PTSD and drinking. Among women (n=136 with past sexual victimization, n=40 no past trauma history), a two-part mixed hurdle model was used to examine daily PTSD and drinking. On days women experienced more intrusive and behavioral avoidance symptoms, they were more likely to drink. For a 2 SD increase in symptoms, there was a 5% increased likelihood of drinking, and for a 2 SD increase in dysphoric symptoms or negative affect, women drank approximately half drink less. Daily-level coping self-efficacy moderated the association between distress and drinking (IRR=0.91, p<0.01). Women who reported less coping drank more as their distress increased on a certain day whereas women who reported more coping drank about the same regardless of distress. Overall, findings suggest that specific PTSD symptoms are associated with higher alcohol use and that these relationships are moderated by daily coping self-efficacy. Implications of these findings for informing models of PTSD/AUD comorbidity, as well as clinical implications will be discussed. PMID:25511723

  1. Interactive orbital proximity operations planning system

    NASA Technical Reports Server (NTRS)

    Grunwald, Arthur J.; Ellis, Stephen R.

    1989-01-01

    An interactive, graphical proximity operations planning system was developed which allows on-site design of efficient, complex, multiburn maneuvers in the dynamic multispacecraft environment about the space station. Maneuvering takes place in, as well as out of, the orbital plane. The difficulty in planning such missions results from the unusual and counterintuitive character of relative orbital motion trajectories and complex operational constraints, which are both time varying and highly dependent on the mission scenario. This difficulty is greatly overcome by visualizing the relative trajectories and the relative constraints in an easily interpretable, graphical format, which provides the operator with immediate feedback on design actions. The display shows a perspective bird's-eye view of the space station and co-orbiting spacecraft on the background of the station's orbital plane. The operator has control over two modes of operation: (1) a viewing system mode, which enables him or her to explore the spatial situation about the space station and thus choose and frame in on areas of interest; and (2) a trajectory design mode, which allows the interactive editing of a series of way-points and maneuvering burns to obtain a trajectory which complies with all operational constraints. Through a graphical interactive process, the operator will continue to modify the trajectory design until all operational constraints are met. The effectiveness of this display format in complex trajectory design is presently being evaluated in an ongoing experimental program.

  2. Proximity Resonance and Localized Surface Plasmons

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Heller, Eric

    2014-03-01

    The collective excitation of conduction electrons in subwavelength nanostructures is known as Localized Surface Plasmon(LSP)[1]. Such plasmon modes has been intensively studied using noble nanoparticles . More recently, the possibility of building terahertz metamaterials supporting such LSP modes has been explored in graphene microribbons and microdisks. Unlike Surface Plasmon Polaritons(SPPs) at metal-insulator interface, LSP can be directly excited by light illumination and holds promise for applications in ultrasensitive biosensing, nano-optical tweezers and improved photovoltaic devices. In this paper, we consider the interaction of two LSPs in the weak coupling regime and show how an effect similar to the proximity resonance in the quantum scattering theory) gives rise to an asymmetric(quadrupole) mode with increased damping rate. The existence of this asymmetric mode relies on a small phase retardation between the two LSPs. This phase retardation, though small, is key to both increased damping rate for the asymmetric mode and reduced damping rate for the symmetric mode. When this small phase retardation is removed by changing the polarization of the exciting light,we show that the asymmetric mode can not be excited and the symmetric mode shows increased damping.

  3. Interactive orbital proximity operations planning system

    NASA Technical Reports Server (NTRS)

    Grunwald, Arthur J.; Ellis, Stephen R.

    1988-01-01

    An interactive graphical proximity operations planning system was developed, which allows on-site design of efficient, complex, multiburn maneuvers in a dynamic multispacecraft environment. Maneuvering takes place in and out of the orbital plane. The difficulty in planning such missions results from the unusual and counterintuitive character of orbital dynamics and complex time-varying operational constraints. This difficulty is greatly overcome by visualizing the relative trajectories and the relevant constraints in an easily interpretable graphical format, which provides the operator with immediate feedback on design actions. The display shows a perspective bird's-eye view of a Space Station and co-orbiting spacecraft on the background of the Station's orbital plane. The operator has control over the two modes of operation: a viewing system mode, which enables the exporation of the spatial situation about the Space Station and thus the ability to choose and zoom in on areas of interest; and a trajectory design mode, which allows the interactive editing of a series of way points and maneuvering burns to obtain a trajectory that complies with all operational constraints. A first version of this display was completed. An experimental program is planned in which operators will carry out a series of design missions which vary in complexity and constraints.

  4. Proximity operations considerations affecting spacecraft design

    NASA Astrophysics Data System (ADS)

    Staas, Steven K.

    Proximity operations can be defined as the maneuvering of two or more spacecraft within 1 nautical mile range, with relative velocity less than 10 feet per second. The passive vehicle is nontranslating and should provide for maintenance of the desired approach attitude. It must accommodate the active (translating) vehicle induced structural loads and performance characteristics (mating hardware tolerances), and support sensor compatibility (transponder, visual targets, etc.). The active vehicle must provide adequate sensor systems (relative state information, field-of-view, redundancy), flight control hardware (thruster sizing, minimal cross-coupling, performance margins, redundancy) and software (reconfigurable, attitude/rate modes, translation and rotation fine control authority) characteristic, and adequate non-propulsive consumables such as power. Operational concerns must be considered. These include the following: (1) the desired approach trajectory and relative orientation; (2) the active vehicle thruster plume effects (forces, torques, contamination) on the passive vehicle; and (3) procedures for contingencies such as loss of communications, sensor or propulsion failures, and target vehicle loss of control.

  5. Proximal spinal muscular atrophy: current orthopedic perspective

    PubMed Central

    Haaker, Gerrit; Fujak, Albert

    2013-01-01

    Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective “survival motor neuron” (SMN) protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. PMID:24399883

  6. Extensor mechanism reconstruction after proximal tibial replacement.

    PubMed

    Oddy, M J; Pendegrass, C J; Goodship, A E; Cannon, S R; Briggs, T W R; Blunn, G W

    2005-06-01

    We developed an in vivo model of the attachment of a patellar tendon to a metal implant to simulate the reconstruction of an extensor mechanism after replacement of the proximal tibia. In 24 ewes, the patellar tendon was attached to a hydroxyapatite (HA)-coated titanium prosthesis. In 12, the interface was augmented with autograft containing cancellous bone and marrow. In the remaining ewes, the interface was not grafted. Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis. With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved. PMID:15911677

  7. Semiconductor detectors with proximity signal readout

    SciTech Connect

    Asztalos, Stephen J.

    2014-01-30

    Semiconductor-based radiation detectors are routinely used for the detection, imaging, and spectroscopy of x-rays, gamma rays, and charged particles for applications in the areas of nuclear and medical physics, astrophysics, environmental remediation, nuclear nonproliferation, and homeland security. Detectors used for imaging and particle tracking are more complex in that they typically must also measure the location of the radiation interaction in addition to the deposited energy. In such detectors, the position measurement is often achieved by dividing or segmenting the electrodes into many strips or pixels and then reading out the signals from all of the electrode segments. Fine electrode segmentation is problematic for many of the standard semiconductor detector technologies. Clearly there is a need for a semiconductor-based radiation detector technology that can achieve fine position resolution while maintaining the excellent energy resolution intrinsic to semiconductor detectors, can be fabricated through simple processes, does not require complex electrical interconnections to the detector, and can reduce the number of required channels of readout electronics. Proximity electrode signal readout (PESR), in which the electrodes are not in physical contact with the detector surface, satisfies this need.

  8. Ranging/tracking system for proximity operations

    NASA Technical Reports Server (NTRS)

    Nilsen, P.; Udalov, S.

    1982-01-01

    The hardware development and testing phase of a hand held radar for the ranging and tracking for Shuttle proximity operations are considered. The radar is to measure range to a 3 sigma accuracy of 1 m (3.28 ft) to a maximum range of 1850 m (6000 ft) and velocity to a 3 sigma accuracy of 0.03 m/s (0.1 ft/s). Size and weight are similar to hand held radars, frequently seen in use by motorcycle police officers. Meeting these goals for a target in free space was very difficult to obtain in the testing program; however, at a range of approximately 700 m, the 3 sigma range error was found to be 0.96 m. It is felt that much of this error is due to clutter in the test environment. As an example of the velocity accuracy, at a range of 450 m, a 3 sigma velocity error of 0.02 m/s was measured. The principles of the radar and recommended changes to its design are given. Analyses performed in support of the design process, the actual circuit diagrams, and the software listing are included.

  9. Proximity induced Superconductivity in Epitaxial Graphene

    NASA Astrophysics Data System (ADS)

    Natterer, Fabian D.; Ha, Jeonghoon; Baek, Hongwoo; Zhang, Duming; Cullen, William; Zhitenev, Nikolai B.; Kuk, Young; Stroscio, Joseph A.

    The intimate electrical contact of a superconductor with a normal metal leads to an exchange of carriers through their boundary. Cooper pairs leak into the normal metal via Andreev reflection and enable the normal metal to acquire superconducting-like properties. The electron-hole conversion process in graphene is prominent due to relativistic quantum mechanics governing low energy chiral carriers in a multi-valley system. In the present experiment, we reveal spatial measurements of the proximity effect in graphene from a graphene-superconductor interface. Superconducting aluminum films were grown on epitaxial graphene on SiC. The aluminum films were discontinuous with networks of trenches in the film morphology reaching down to the substrate to exposed graphene terraces. Scanning tunneling spectra measured on the graphene terraces show a clear decay of the superconducting gap width with increasing separation from the graphene-aluminum edges. The decay length for the superconducting energy gap extends beyond 400 nm. Subtle deviations in the exponentially decaying energy gap were also observed on a much smaller length scale of tens of nanometers. Funding from SNSF (project 158468), NIST/CNST Grant 70NANB10H193, and KRF-2010-00349.

  10. Imaging of rectus femoris proximal tendinopathies.

    PubMed

    Pesquer, Lionel; Poussange, Nicolas; Sonnery-Cottet, Bertrand; Graveleau, Nicolas; Meyer, Philippe; Dallaudiere, Benjamin; Feldis, Matthieu

    2016-07-01

    The rectus femoris is the most commonly injured muscle of the anterior thigh among athletes, especially soccer players. Although the injury pattern of the muscle belly is well documented, less is known about the anatomy and specific lesions of the proximal tendons. For each head, three distinctive patterns may be encountered according to the location of the injury, which can be at the enthesis, within the tendon, or at the musculotendinous junction. In children, injuries correspond most commonly to avulsion of the anteroinferior iliac spine from the direct head and can lead to subspine impingement. Calcific tendinitis and traumatic tears may be encountered in adults. Recent studies have shown that traumatic injuries of the indirect head may be underdiagnosed and that injuries of both heads may have a surgical issue. Finally, in the case of tears, functional outcome and treatment may vary if the rupture involves one or both tendons and if the tear is partial or complete. Thus, it is mandatory for the radiologist to know the different ultrasound and magnetic resonance imaging (MRI) patterns of these lesions in order to provide accurate diagnosis and treatment. The purpose of this article is to recall the anatomy of the two heads of rectus femoris, describe a reliable method of assessment with ultrasound and MRI and know the main injury patterns, through our own experience and literature review. PMID:26956398

  11. Bilateral non-osteochondroma-related proximal tibiofibular synostosis.

    PubMed

    Wakayama, Takanori; Imanishi, Jungo; Yazawa, Yasuo; Okubo, Taketo; Kaneko, Kazuo

    2014-12-01

    We report the case of a 67-year-old male with bilateral proximal tibiofibular synostosis, presenting with unilateral symptoms. The patient complained of pain around the left fibular head, which was attributed to incomplete bone bridging between the proximal tibia and fibula; he underwent proximal fibular head resection, which alleviated the pain and improved knee mobility. Eleven months later, the patient continued to be pain-free and did not experience any adverse effects. An examination of this case and a review of similar cases revealed that participation in sport activities such as long-distance running may be one of the causes of proximal tibiofibular synostosis. In this report, we have also reconsidered the classification of proximal tibiofibular synostosis and provided information for a better understanding of this unusual condition. PMID:24915740

  12. Preventing Proximal Adjacent Level Kyphosis With Strap Stabilization.

    PubMed

    Zaghloul, Khaled M; Matoian, Brett J; Denardin, Nicholas B; Patel, Vikas V

    2016-07-01

    A substantial proportion of patients develop proximal junctional kyphosis following spinal surgery. To combat this postoperative change, several techniques have focused on maintaining the structural integrity of adjacent spinal levels and adapting the proximal end of the fusion construct to accommodate the increased mechanical stressors produced by long spinal fusion. The use of Mersilene tape (Ethicon, Somerville, New Jersey) for spine and orthopedic surgery is well documented, although considerably less is known about its use for preventing proximal junctional kyphosis. This article describes a proposed technique using Mersilene tape to provide a check-rein strap stabilization at the proximal end of fusion constructs. Initial data suggest that use of this technique may prevent formation of proximal junctional kyphosis. [Orthopedics. 2016; 39(4):e794-e799.]. PMID:27158827

  13. Molecular interactions between albumin and proximal tubular cells.

    PubMed

    Brunskill, N J

    1998-01-01

    In glomerular diseases the filtration of excess proteins into the proximal tubule, together with their subsequent reabsorption may represent an important pathological mechanism underlying progressive renal scarring. The most prominent protein in glomerular filtrate, albumin, is reabsorbed by receptor-mediated endocytosis by proximal tubular cells. It binds both to scavenger-type receptors and to megalin in the proximal tubule. Some of these receptors appear to be shared with other cell types, particularly endothelial cells. The endocytic uptake of albumin is subjected to complex hormonal and enzymatic regulation. In addition to being reabsorbed in the proximal tubule, albumin may act as a signalling molecule in these cells, and may induce the expression of numerous pro-inflammatory genes. Modulation of the interaction of albumin with proximal tubular cells may eventually prove to be of therapeutic importance in the treatment of renal diseases. PMID:9807019

  14. Mechanisms of albumin uptake by proximal tubular cells.

    PubMed

    Brunskill, N

    2001-01-01

    The likely role of albumin in the induction tubulo-interstitial injury in proteinuria has stimulated considerable interest in the entry of albumin into the proximal tubule and its subsequent uptake by proximal tubular cells. Currently, there is considerable controversy over the degree of glomerular permeability to albumin. After filtration, however, albumin binds to megalin and cubulin, two giant receptors in the apical membrane of proximal tubular cells. Albumin is subsequently re-absorbed by proximal tubular cells by receptor-mediated endocytosis, a process subject to complex regulation. The interaction of albumin with proximal tubule cells also leads to the generation of intracellular signals. The understanding of these pathways may provide important insights into the pathogenesis of renal scarring in proteinuria. PMID:11158855

  15. Estimation of optical proximity effect caused by mask fabrication error

    NASA Astrophysics Data System (ADS)

    Kamon, Kazuya; Hanawa, Tetsuro; Moriizumi, Koichi

    1997-07-01

    To get wide lithography latitudes in ULSI fabrication, an optical proximity correction system is being widely used. We previously demonstrated that the optical proximity effect is highly dependent on beam interference conditions. By using an aperture with a spindle shaped opaque region and a controlling interference beam number optimized for imaging, we can obtain a high correction accuracy of less than +/- 0.01 micrometers for all kinds of pattern. To put the optical proximity correction into practical use, we must fabricate the corrected mask either by an EB or a laser writing system. But during mask writing, there is another problematic proximity effect. The optical proximity effect caused by mask fabrication error is becoming a serious problem. In this paper, we estimate the optical proximity effect caused by mask fabrication error. For EB writing, the mask feature size of 0.35 micrometers line changes dramatically in a space less than 0.8 micrometers in size; this is not tolerable. For a large pitch pattern, modified illumination reduces the DOF to 0 micrometers . Otherwise, laser writing stably fabricates a mask feature size for a 0.35 micrometers line, and the modified illumination reduces the optical proximity effect. This resist feature fluctuation is binary, so, correcting the mask pattern is easy. Although, it was wrongly thought that for larger pitch pattern, the DOF was reduced by the modified illumination, the DOF reduction actually came from the combination of the two proximity effects. Using an accurate mask produced by a laser writer, we do not observe any DOF reduction in modified illumination. Moreover, this has led to development of an optical proximity correction system with EB proximity correction.

  16. Hypospadias and Residential Proximity to Pesticide Applications

    PubMed Central

    Yang, Wei; Roberts, Eric M.; Kegley, Susan E.; Wolff, Craig; Guo, Liang; Lammer, Edward J.; English, Paul; Shaw, Gary M.

    2013-01-01

    BACKGROUND: Experimental evidence suggests pesticides may be associated with hypospadias. OBJECTIVE: Examine the association of hypospadias with residential proximity to commercial agricultural pesticide applications. METHODS: The study population included male infants born from 1991 to 2004 to mothers residing in 8 California counties. Cases (n = 690) were ascertained by the California Birth Defects Monitoring Program; controls were selected randomly from the birth population (n = 2195). We determined early pregnancy exposure to pesticide applications within a 500-m radius of mother’s residential address, using detailed data on applications and land use. Associations with exposures to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for maternal race or ethnicity and age and infant birth year. RESULTS: Forty-one percent of cases and controls were classified as exposed to 57 chemical groups and 292 chemicals. Despite >500 statistical comparisons, there were few elevated odds ratios with confidence intervals that excluded 1 for chemical groups or specific chemicals. Those that did were for monochlorophenoxy acid or ester herbicides; the insecticides aldicarb, dimethoate, phorate, and petroleum oils; and adjuvant polyoxyethylene sorbitol among all cases; 2,6-dinitroaniline herbicides, the herbicide oxyfluorfen, and the fungicide copper sulfate among mild cases; and chloroacetanilide herbicides, polyalkyloxy compounds used as adjuvants, the insecticides aldicarb and acephate, and the adjuvant nonyl-phenoxy-poly(ethylene oxy)ethanol among moderate and severe cases. Odds ratios ranged from 1.9 to 2.9. CONCLUSIONS: Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations. PMID:24167181

  17. Nanocrystal Bioassembly: Asymmetry, Proximity, and Enzymatic Manipulation

    SciTech Connect

    Claridge, Shelley A.

    2008-05-01

    Research at the interface between biomolecules and inorganic nanocrystals has resulted in a great number of new discoveries. In part this arises from the synergistic duality of the system: biomolecules may act as self-assembly agents for organizing inorganic nanocrystals into functional materials; alternatively, nanocrystals may act as microscopic or spectroscopic labels for elucidating the behavior of complex biomolecular systems. However, success in either of these functions relies heavily uponthe ability to control the conjugation and assembly processes.In the work presented here, we first design a branched DNA scaffold which allows hybridization of DNA-nanocrystal monoconjugates to form discrete assemblies. Importantly, the asymmetry of the branched scaffold allows the formation of asymmetric2assemblies of nanocrystals. In the context of a self-assembled device, this can be considered a step toward the ability to engineer functionally distinct inputs and outputs.Next we develop an anion-exchange high performance liquid chromatography purification method which allows large gold nanocrystals attached to single strands of very short DNA to be purified. When two such complementary conjugates are hybridized, the large nanocrystals are brought into close proximity, allowing their plasmon resonances to couple. Such plasmon-coupled constructs are of interest both as optical interconnects for nanoscale devices and as `plasmon ruler? biomolecular probes.We then present an enzymatic ligation strategy for creating multi-nanoparticle building blocks for self-assembly. In constructing a nanoscale device, such a strategy would allow pre-assembly and purification of components; these constructs can also act as multi-label probes of single-stranded DNA conformational dynamics. Finally we demonstrate a simple proof-of-concept of a nanoparticle analog of the polymerase chain reaction.

  18. Coupled water transport by rat proximal tubule.

    PubMed

    Green, R; Giebisch, G; Unwin, R; Weinstein, A M

    1991-12-01

    Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to examine water reabsorption by this epithelium. Osmolality of the luminal solution was varied with changes in NaCl concentration and by the addition of raffinose. Capillary perfusates contained either low (2 g/dl) or high (16 g/dl) concentrations of albumin. We used low-bicarbonate perfusates for both lumen and capillary so that we might apply the nonequilibrium thermodynamic model of transport for a single solute (NaCl) to interpret our observations. Linear regression with the volume flux equation Jv = -Lp delta II - Lp sigma delta C + Jav (where Jv is volume flux, Lp is hydraulic conductance, delta II is oncotic force, sigma is osmotic reflection coefficient, delta C is salt concentration difference, and Jav is the component of Jv not attributed to transepithelial hydrostatic or osmotic forces) revealed a tubule water permeability (Pf = 0.11 +/- 0.01 cm/s) and a sigma (0.74 +/- 0.08) in agreement with previous determinations. These transport parameters were unaffected by changes in peritubular protein. We also found that Jav was substantial, approximately three-fourths of the rate of isotonic transport under these perfusion conditions. Further, this component of water transport nearly doubled with the transition from low- to high-protein peritubular capillary perfusion. When expressed as a capacity for water reabsorption against an osmotic gradient, the salt concentration differences required to null volume flux were 13.2 +/- 2.4 and 29.4 +/- 4.0 mosmol/kgH2O under low and high peritubular protein. Our data suggest that this protein effect is, most likely, an increase in solute transport by the tubule epithelial cells. PMID:1750518

  19. Transport Magnetic Proximity Effects in Platinum

    NASA Astrophysics Data System (ADS)

    Huang, Ssu-Yen

    2013-03-01

    Platinum (Pt) metal, being non-magnetic and having a strong spin-orbit coupling interaction, has been central in detecting pure spin current and establishing most of the recent spin-based phenomena. Thus, it is important to ascertain the transport and magnetic characteristics of thin Pt films in contact with a ferromagnet. In this work, we use both electric and thermal means to conclusively show the transport magnetic proximity effects (MPE) of thin Pt film in contact with ferromagnetic insulator YIG. At thicknesses comparable to, and less than, the spin diffusion length, the strong ferromagnetic characteristics in Pt films on YIG are indistinguishable from those of ferromagnetic permalloy on YIG. The MPE occurs at the interface and decreases exponentially away from the interface, concentrating in only a few monolayers. As a result, the pure spin current detected by a thin Pt is tainted with a spin polarized current. The pure spin current phenomena, such as the inverse spin Hall effect and the spin Seebeck effect, have been contaminated with the anomalous Hall effect and the anomalous Nernst effect respectively. These results raise serious questions about the suitability, and the validity, of using Pt in establishing pure spin current phenomena; on the other hand, a much stronger spin-based effect can be induced by the MPE at the interface. This research is in collaboration with X. Fin, Y. P. Chen, J. Wu, and J. Q. Xiao (University of Delaware), T. Y. Chen (Arizona State University) and D. Qu, W. G. Wang, and C. L. Chien (The Johns Hopkins University).

  20. Promoting Models

    NASA Astrophysics Data System (ADS)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  1. Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function

    PubMed Central

    May, Rebecca M.; Okumura, Mariko; Hsu, Chin-Jung; Bassiri, Hamid; Yang, Enjun; Rak, Gregory; Mace, Emily M.; Philip, Naomi H.; Zhang, Weiguo; Baumgart, Tobias; Orange, Jordan S.; Nichols, Kim E.

    2013-01-01

    Signaling pathways leading to natural killer (NK)–cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating receptors. We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is recruited to microclusters at the plasma membrane in activated NK cells and that this is required for initiation of downstream signaling and multiple NK-cell effector functions in vitro and in vivo. Surprisingly, we found that 2 types of proximal signaling complexes involving SLP-76 were formed. In addition to the canonical membrane complex formed between SLP-76 and linker for activation of T cells (LAT) family members, a novel LAT family–independent SLP-76–dependent signaling pathway was identified. The LAT family–independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-promoting adaptor protein (ADAP). Both the LAT family–dependent and ADAP-dependent pathway contributed to interferon-gamma production and cytotoxicity; however, they were not essential for other SLP-76–dependent events, including phosphorylation of AKT and extracellular signal–related kinase and cellular proliferation. These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function. PMID:23407547

  2. Repair of esophageal atresia with proximal fistula using endoscopic magnetic compression anastomosis (magnamosis) after staged lengthening.

    PubMed

    Dorman, Robert M; Vali, Kaveh; Harmon, Carroll M; Zaritzky, Mario; Bass, Kathryn D

    2016-05-01

    We describe the treatment of a patient with long-gap esophageal atresia with an upper pouch fistula, mircogastria and minimal distal esophageal remnant. After 4.5 months of feeding via gastrostomy, a proximal fistula was identified by bronchoscopy and a thoracoscopic modified Foker procedure was performed reducing the gap from approximately 7-5 cm over 2 weeks of traction. A second stage to ligate the fistula and suture approximate the proximal and distal esophagus resulted in a gap of 1.5 cm. IRB and FDA approval was then obtained for endoscopic placement of 10-French catheter mounted magnets in the proximal and distal pouches promoting a magnetic compression anastomosis (magnamosis). Magnetic coupling occurred at 4 days and after magnet removal at 13 days an esophagram demonstrated a 10 French channel without leak. Serial endoscopic balloon dilation has allowed drainage of swallowed secretions as the baby learns bottling behavior at home. PMID:27012861

  3. Cancer rates after the Three Mile Island nuclear accident and proximity of residence to the plant.

    PubMed Central

    Hatch, M C; Wallenstein, S; Beyea, J; Nieves, J W; Susser, M

    1991-01-01

    BACKGROUND: In the light of a possible link between stress and cancer promotion or progression, and of previously reported distress in residents near the Three Mile Island (TMI) nuclear power plant, we attempted to evaluate the impact of the March 1979 accident on community cancer rates. METHODS: Proximity of residence to the plant, which related to distress in previous studies, was taken as a possible indicator of accident stress; the postaccident pattern in cancer rates was examined in 69 "study tracts" within a 10-mile radius of TMI, in relation to residential proximity. RESULTS: A modest association was found between postaccident cancer rates and proximity (OR = 1.4; 95% CI = 1.3, 1.6). After adjusting for a gradient in cancer risk prior to the accident, the odds ratio contrasting those closest to the plant with those living farther out was 1.2 (95% CI = 1.0, 1.4). A postaccident increase in cancer rates near the Three Mile Island plant was notable in 1982, persisted for another year, and then declined. Radiation emissions, as modeled mathematically, did not account for the observed increase. CONCLUSION: Interpretation in terms of accident stress is limited by the lack of an individual measure of stress and by uncertainty about whether stress has a biological effect on cancer in humans. An alternative mechanism for the cancer increase near the plant is through changes in care-seeking and diagnostic practice arising from postaccident concern. PMID:2029040

  4. Promoting Health.

    ERIC Educational Resources Information Center

    Mechanic, David

    1990-01-01

    Argues that culture change or modification of the social structure is necessary for effective health promotion because health behavior is closely tied to basic group structures and processes. Examines the health attitudes of Mormons, low income and minority groups, and developing Islamic nations, emphasizing attitudes towards education and women.…

  5. Differentiated kidney epithelial cells repair injured proximal tubule.

    PubMed

    Kusaba, Tetsuro; Lalli, Matthew; Kramann, Rafael; Kobayashi, Akio; Humphreys, Benjamin D

    2014-01-28

    Whether kidney proximal tubule harbors a scattered population of epithelial stem cells is a major unsolved question. Lineage-tracing studies, histologic characterization, and ex vivo functional analysis results conflict. To address this controversy, we analyzed the lineage and clonal behavior of fully differentiated proximal tubule epithelial cells after injury. A CreER(T2) cassette was knocked into the sodium-dependent inorganic phosphate transporter SLC34a1 locus, which is expressed only in differentiated proximal tubule. Tamoxifen-dependent recombination was absolutely specific to proximal tubule. Clonal analysis after injury and repair showed that the bulk of labeled cells proliferate after injury with increased clone size after severe compared with mild injury. Injury to labeled proximal tubule epithelia induced expression of CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative epithelial stem cells in the human kidney. Similar results were observed in cultured proximal tubules, in which labeled clones proliferated and expressed dedifferentiation and injury markers. When mice with completely labeled kidneys were subject to injury and repair there was no dilution of fate marker despite substantial proliferation, indicating that unlabeled progenitors do not contribute to kidney repair. During nephrogenesis and early kidney growth, single proximal tubule clones expanded, suggesting that differentiated cells also contribute to tubule elongation. These findings provide no evidence for an intratubular stem-cell population, but rather indicate that terminally differentiated epithelia reexpress apparent stem-cell markers during injury-induced dedifferentiation and repair. PMID:24127583

  6. Closed proximal muscle rupture of the biceps brachii in wakeboarders.

    PubMed

    Pascual-Garrido, Cecilia; Swanson, Britta L; Bannar, Stephen M

    2012-06-01

    Closed proximal muscle rupture of the biceps brachii is a rare injury. In this report, two cases of closed proximal muscle rupture of the biceps brachii after wakeboard traumas are described. Both patients presented with a swollen arm, weakness during flexion, and a mass in the affected forearm. Magnetic resonance imaging showed displacement of the biceps brachii into the forearm. The rupture was successfully treated with muscle removal in one case and muscle repair in the other. In patients with a wakeboard trauma and similar presentations, closed proximal muscle rupture of the biceps brachii should be suspected. PMID:21877295

  7. Maximal Expression of the Evolutionarily Conserved Slit2 Gene Promoter Requires Sp1.

    PubMed

    Saunders, Jacquelyn; Wisidagama, D Roonalika; Morford, Travis; Malone, Cindy S

    2016-08-01

    Slit2 is a neural axon guidance and chemorepellent protein that stimulates motility in a variety of cell types. The role of Slit2 in neural development and neoplastic growth and migration has been well established, while the genetic mechanisms underlying regulation of the Slit2 gene have not. We identified the core and proximal promoter of Slit2 by mapping multiple transcriptional start sites, analyzing transcriptional activity, and confirming sequence homology for the Slit2 proximal promoter among a number of species. Deletion series and transient transfection identified the Slit2 proximal promoter as within 399 base pairs upstream of the start of transcription. A crucial region for full expression of the Slit2 proximal promoter lies between 399 base pairs and 296 base pairs upstream of the start of transcription. Computer modeling identified three transcription factor-binding consensus sites within this region, of which only site-directed mutagenesis of one of the two identified Sp1 consensus sites inhibited transcriptional activity of the Slit2 proximal promoter (-399 to +253). Bioinformatics analysis of the Slit2 proximal promoter -399 base pair to -296 base pair region shows high sequence conservation over twenty-two species, and that this region follows an expected pattern of sequence divergence through evolution. PMID:26456684

  8. Effective molarity redux: Proximity as a guiding force in chemistry and biology.

    PubMed

    Hobert, Elissa M; Doerner, Amy E; Walker, Allison S; Schepartz, Alanna

    2013-08-01

    The cell interior is a complex and demanding environment. An incredible variety of molecules jockey to identify the correct position-the specific interactions that promote biology that are hidden among countless unproductive options. Ensuring that the business of the cell is successful requires sophisticated mechanisms to impose temporal and spatial specificity-both on transient interactions and their eventual outcomes. Two strategies employed to regulate macromolecular interactions in a cellular context are co-localization and compartmentalization. Macromolecular interactions can be promoted and specified by localizing the partners within the same subcellular compartment, or by holding them in proximity through covalent or non-covalent interactions with proteins, lipids, or DNA- themes that are familiar to any biologist. The net result of these strategies is an increase in effective molarity: the local concentration of a reactive molecule near its reaction partners. We will focus on this general mechanism, employed by Nature and adapted in the lab, which allows delicate control in complex environments: the power of proximity to accelerate, guide, or otherwise influence the reactivity of signaling proteins and the information that they encode. PMID:25418998

  9. Technical tips: dualplate fixation technique for comminuted proximal humerus fractures.

    PubMed

    Choi, Sungwook; Kang, Hyunseong; Bang, Hyeongsig

    2014-08-01

    The authors report dualplate fixation technique for providing stable fixation in comminuted proximal humerus fractures. This technique has been used for proximal humerus fractures with metaphyseal comminution and provides excellent anatomical reduction and neck shaft angle (NSA). The recently locking plate is clinically more widely used due to its small size, low rigidity, high elasticity, and biomechanical properties such as fixed initial angle and rotational stability. However, in severely comminuted complex type proximal metaphyseal humerus fractures, the use of locking plate alone does not provide stable fixation, leading to complications such as varus collapse, anterior-posterior angulation, screw cutout, nonunion, malunion, and metal failure. Therefore, a more robust and enhanced fixation method, the dual plating technique using the locking compression plate (Proximal Humeral Internal Locking System and Variable Angle Locking Compression Plate) was developed. PMID:24813097

  10. Light-operated proximity detector with linear output

    DOEpatents

    Simpson, Marc L.; McNeilly, David R.

    1985-01-01

    A light-operated proximity detector is described in which reflected light intensity from a surface whose proximity to the detector is to be gauged is translated directly into a signal proportional to the distance of the detector from the surface. A phototransistor is used to sense the reflected light and is connected in a detector circuit which maintains the phototransistor in a saturated state. A negative feedback arrangement using an operational amplifier connected between the collector and emitter of the transistor provides an output at the output of the amplifier which is linearly proportional to the proximity of the surface to the detector containing the transistor. This direct proportional conversion is true even though the light intensity is varying with the proximity in proportion to the square of the inverse of the distance. The detector may be used for measuring the distance remotely from any target surface.

  11. Light-operated proximity detector with linear output

    DOEpatents

    Simpson, M.L.; McNeilly, D.R.

    1984-01-01

    A light-operated proximity detector is described in which reflected light intensity from a surface whose proximity to the detector is to be gauged is translated directly into a signal proportional to the distance of the detector from the surface. A phototransistor is used to sense the reflected light and is connected in a detector circuit which maintains the phtotransistor in a saturated state. A negative feedback arrangement using an operational amplifier connected between the collector and emitter of the transistor provides an output at the output of the amplifier which is linearly proportional to the proximity of the surface to the detector containing the transistor. This direct proportional conversion is true even though the light intensity is varying with the proximity in proportion to the square of the inverse of the distance. The detector may be used for measuring the distance remotely from any target surface.

  12. An unusual case of glipizide-induced proximal myopathy

    PubMed Central

    Das, Saibal; Ramasamy, Anand; De, Soumyadip; Mondal, Somnath

    2016-01-01

    This case report outlines a very rare case of glipizide-induced severe proximal myopathy in a 61-year-old diabetic man. After taking 10 mg glipizide for 5 months, diabetes was well controlled but the patient presented with progressive proximal muscle weakness in all the four limbs. Clinical examination and relevant investigations suggested it to be a case of proximal myopathy and might be drug induced. De-challenge was done and was treated resulting in reversal of the diseased state. After 3 more months, controlled re-challenge was done and there was recurrence of proximal muscle weakness. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition and Naranjo adverse drug reaction probability scale suggested that it was “probable” that glipizide was responsible for the development of myopathy in this patient. PMID:27440956

  13. An unusual case of glipizide-induced proximal myopathy.

    PubMed

    Das, Saibal; Ramasamy, Anand; De, Soumyadip; Mondal, Somnath

    2016-01-01

    This case report outlines a very rare case of glipizide-induced severe proximal myopathy in a 61-year-old diabetic man. After taking 10 mg glipizide for 5 months, diabetes was well controlled but the patient presented with progressive proximal muscle weakness in all the four limbs. Clinical examination and relevant investigations suggested it to be a case of proximal myopathy and might be drug induced. De-challenge was done and was treated resulting in reversal of the diseased state. After 3 more months, controlled re-challenge was done and there was recurrence of proximal muscle weakness. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition and Naranjo adverse drug reaction probability scale suggested that it was "probable" that glipizide was responsible for the development of myopathy in this patient. PMID:27440956

  14. Interracial Ratios and Proximity in Dormitories: Attitudes of University Students

    ERIC Educational Resources Information Center

    Bennett, Don C.

    1974-01-01

    A survey technique was used to investigate black and white undergraduate students' attitudes toward the minimum number of one's own race needed for comfort in dormitory residency and the relationship of proximity of one's race toward this number. (MLB)

  15. Proximity induced Shiba states in an organic radical molecular junction

    NASA Astrophysics Data System (ADS)

    Island, Joshua; Gaudenzi, Rocco; Burzuri, Enrique; van der Zant, Herre

    Superconductors containing magnetic impurities lead to interesting phenomena derived from the interaction between Cooper pairing and Kondo screening. Here, we present measurements on proximity induced superconducting break-junctions hosting a magnetic impurity in the form of a neutral and stable, all organic radical molecule. Transport measurements reveal sub-gap excitations which are characteristic of a spin-induced, Yu-Shiba-Rusniov (Shiba) bound state due to the interaction of the radical's unpaired spin with a strongly coupled, proximity-induced superconductor. We show that by applying an external magnetic field to suppress the proximity induced superconductivity, a zero bias peak emerges signaling Kondo screening of the radical's unpaired spin coupled to normal leads. Our results show that Shiba states are a robust feature of the interaction between a magnetic impurity and a proximity induced superconducting junction. This work is supported by the Dutch Organization for Fundamental Research on Matter (NWO/OCW).

  16. 1. General view to southwest showing proximity of house to ...

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

    1. General view to southwest showing proximity of house to bridge and north elevation of house. - Locke Avenue Bridge, Bridge Tender's House, East side of Locke Avenue, 12 feet south of Locke Avenue Bridge, Swedesboro, Gloucester County, NJ

  17. Existence of best proximity pairs and equilibrium pairs

    NASA Astrophysics Data System (ADS)

    Kim, Won Kyu; Lee, Kyoung Hee

    2006-04-01

    In this paper, using the fixed point theorem for Kakutani factorizable multifunctions, we shall prove new existence theorems of best proximity pairs and equilibrium pairs for free abstract economies, which include the previous fixed point theorems and equilibrium existence theorems.

  18. Perinatal mortality and residential proximity to an industrial park.

    PubMed

    Sarov, Batia; Bentov, Yaakov; Kordysh, Ella; Karakis, Isabella; Bolotin, Arkady; Hershkovitz, Reli; Belmaker, Ilana

    2008-01-01

    The authors' objective was to determine whether residential proximity to an industrial park (IP) is associated with increased perinatal mortality (PM). This semiecological study included 63,850 delivered births with 840 cases of PM (1995-2000). The authors categorized the study populations by ethnicity (ie, Bedouin and Jewish) and type of locality. Residential distance from the IP served as a surrogate indicator of exposure. Among Bedouin newborns, proximity to the IP was associated with increased PM rates (relative risk = 1.45; 95% confidence interval = 1.22-1.72). The excess in PM was not related to maternal or newborn physical characteristics that the authors observed. The risk of PM and its components in the Jewish localities was not associated with IP proximity. The association between residential proximity to the IP and excess in PM among only Bedouin newborns may be related to vulnerability caused by the nomadic nature of the society. PMID:18479994

  19. Challenger's RMS arm grasps SPAS-01 during proximity operations

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Challenger's remote manipulator system (RMS) arm grasps Shuttle pallet satellite (SPAS-01) during proximity operations. The frame shows a number of reflections on the window, located overhead in the aft flight deck.

  20. Proximity superconductivity in ballistic graphene at high magnetic fields

    NASA Astrophysics Data System (ADS)

    Prance, J. R.; Ben Shalom, M.; Zhu, M. J.; Fal'Ko, V. I.; Mishchenko, A.; Kretinin, A. V.; Novoselov, K. S.; Woods, C. R.; Watanabe, K.; Taniguchi, T.; Geim, A. K.

    We present measurements of the superconducting proximity effect in graphene-based Josephson junctions with a mean free path of several microns, which exceeds the junctions' length. The junctions exhibit low contact resistance and large supercurrents. We observe Fabry-Pérot oscillations in the normal-state resistance and the critical current of the junctions. The proximity effect is mostly suppressed in magnetic fields of <10 mT showing the conventional Fraunhofer interference pattern; however, unexpectedly, a weak proximity effect survives in magnetic fields as high as 1 T. Superconducting states randomly appear and disappear as a function of field and carrier concentration, and each exhibits a supercurrent carrying capacity close to the universal limit of e Δ/h where Δ is the superconducting gap of the contacts. We attribute the high-field supercurrent to mesoscopic Andreev states that persist near graphene edges. Our work reveals new proximity regimes that can be controlled by quantum confinement and cyclotron motion.

  1. Semi-rigid ureteroscopy: Proximal versus distal ureteral stones

    PubMed Central

    Alameddine, Mahmoud; Azab, Mohamad M.; Nassir, Anmar A.

    2016-01-01

    Objective: To evaluate the safety and efficacy of semi-rigid ureteroscopy in proximal and distal ureteral stones, and to compare the operative and perioperative characteristics between the two stone groups. Materials and Methods: We retrospectively reviewed the medical records of patients who underwent semi-rigid ureteroscopy for management of ureteral stones at the International Medical Center between June 2007 and September 2012. All stones were fragmented using Holmium: yttrium-aluminum-garnet (YAG) laser lithotripter. Stones located above the pelvic brim are considered proximal and below it are distal. Results: One hundred and ninety-one patients were included. One hundred and three patients (54%) underwent ureteroscopy for proximal stones and 88 (46%) for distal stones. The stone size in the proximal group was 10 mm (±5.5) versus 8.6 mm (±5) in the distal group. The initial stone-free rate for proximal and distal calculi were 89–98.2%, respectively. The perioperative complication rate was higher in the proximal group 10% compared to the distal group which is 1.5% (P = 0.06). Both groups have the same average of hospital stay 1.2 days. Conclusion: Although there is a clinical difference between proximal and distal calculi groups in terms of complication and stone-free rates, this difference remained statistically insignificant (P = 0.06). Using a smaller caliber semi-rigid ureteroscopy combined with Holmium-YAG laser can be carried out as a day care procedure and showed a slightly higher risk in patients with proximal ureteral calculi which should be explained to the patient PMID:26834409

  2. Extensive arterial aneurysm formation proximal to ligated arteriovenous fistula.

    PubMed Central

    Graham, J M; McCollum, C H; Crawford, E S; DeBakey, M E

    1980-01-01

    As a result of abnormal flow patterns and hyperdynamic flow in arteries proximal to an arteriovenous fistula a particular susceptibility to atherosclerotic changes and aneurysmal deterioration develops. In the following report two patients are presented in which chronic arteriovenous fistulas existed for 15 and 33 years prior to correction. Each patient developed extensive and progressive aneurysmal dilation of the proximal arterial tree and subsequently required surgical resection and graft replacement. Images Fig. 1. Fig. 2. Fig. 3. PMID:6444798

  3. Tubular proteinuria in patients with HNF1α mutations: HNF1α drives endocytosis in the proximal tubule.

    PubMed

    Terryn, Sara; Tanaka, Karo; Lengelé, Jean-Philippe; Olinger, Eric; Dubois-Laforgue, Danièle; Garbay, Serge; Kozyraki, Renata; Van Der Smissen, Patrick; Christensen, Erik I; Courtoy, Pierre J; Bellanné-Chantelot, Christine; Timsit, José; Pontoglio, Marco; Devuyst, Olivier

    2016-05-01

    Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor expressed in the liver, pancreas, and proximal tubule of the kidney. Mutations of HNF1α cause an autosomal dominant form of diabetes mellitus (MODY-HNF1A) and tubular dysfunction. To gain insights into the role of HNF1α in the proximal tubule, we analyzed Hnf1a-deficient mice. Compared with wild-type littermates, Hnf1a knockout mice showed low-molecular-weight proteinuria and a 70% decrease in the uptake of β2-microglobulin, indicating a major endocytic defect due to decreased expression of megalin/cubilin receptors. We identified several binding sites for HNF1α in promoters of Lrp2 and Cubn genes encoding megalin and cubilin, respectively. The functional interaction of HNF1α with these promoters was shown in C33 epithelial cells lacking endogenous HNF1α. Defective receptor-mediated endocytosis was confirmed in proximal tubule cells from these knockout mice and could be rescued by transfection of wild-type but not mutant HNF1α. Transfection of human proximal tubule HK2 cells with HNF1α was able to upregulate megalin and cubilin expression and to increase endocytosis of albumin. Low-molecular-weight proteinuria was consistently detected in individuals with HNF1A mutations compared with healthy controls and patients with non-MODY-HNF1A diabetes mellitus. Thus, HNF1α plays a key role in the constitutive expression of megalin and cubilin, hence regulating endocytosis in the proximal tubule of the kidney. These findings provide new insight into the renal phenotype of individuals with mutations of HNF1A. PMID:27083284

  4. Psychological responses to the proximity of climate change

    NASA Astrophysics Data System (ADS)

    Brügger, Adrian; Dessai, Suraje; Devine-Wright, Patrick; Morton, Thomas A.; Pidgeon, Nicholas F.

    2015-12-01

    A frequent suggestion to increase individuals' willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences, that is, those that are close in space and time. But previous studies that have tested this proximizing approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualization of the proximizing approach within established psychological research suggests that, depending on the particular theoretical perspective one takes on this issue, and on specific individual characteristics suggested by these perspectives, proximizing can bring about the intended positive effects, can have no (visible) effect or can even backfire. Thus, the effects of proximizing are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role that psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions.

  5. Design and Clinical Application of Proximal Humerus Memory Connector

    NASA Astrophysics Data System (ADS)

    Xu, Shuo-Gui; Zhang, Chun-Cai

    2011-02-01

    Treatment for comminuted proximal humerus fractures and nonunions are a substantial challenge for orthopedic surgeons. Plate and screw fixation does not provide enough stability to allow patients to begin functional exercises early after surgery. Using shape memory material nickel titanium alloy, we designed a new device for treating severe comminuted proximal humerus fractures that accommodates for the anatomical features of the proximal humerus. Twenty-two cases of comminuted fracture, malunion, and nonunion of the proximal humerus were treated with the proximal humeral memory connector (PHMC). No external fixation was needed after the operation and patients began active shoulder exercises an average of 8 days after the operation. Follow-up evaluation (mean 18.5 months) revealed that bone healing with lamellar bone formation occurred an average of 3.6 months after surgery for the fracture cases and 4.5 months after surgery for the nonunion cases. Average shoulder function was 88.5 according to the criteria of Michael Reese. PHMC is an effective new device to treat comminuted proximal humerus fractures and nonunions. The use of this device may reduce the need for shoulder joint arthroplasty.

  6. Sprouty/FGF signaling regulates the proximal-distal feather morphology and the size of dermal papillae.

    PubMed

    Yue, Zhicao; Jiang, Ting Xin; Wu, Ping; Widelitz, Randall B; Chuong, Cheng Ming

    2012-12-01

    In a feather, there are distinct morphologies along the proximal-distal axis. The proximal part is a cylindrical stalk (calamus), whereas the distal part has barb and barbule branches. Here we focus on what molecular signaling activity can modulate feather stem cells to generate these distinct morphologies. We demonstrate the drastic tissue remodeling during feather cycling which includes initiation, growth and resting phases. In the growth phase, epithelial components undergo progressive changes from the collar growth zone to the ramogenic zone, to maturing barb branches along the proximal-distal axis. Mesenchymal components also undergo progressive changes from the dermal papilla, to the collar mesenchyme, to the pulp along the proximal-distal axis. Over-expression of Spry4, a negative regulator of receptor tyrosine kinases, promotes barb branch formation at the expense of the epidermal collar. It even induces barb branches from the follicle sheath (equivalent to the outer root sheath in hair follicles). The results are feathers with expanded feather vane regions and small or missing proximal feather shafts (the calamus). Spry4 also expands the pulp region while reducing the size of dermal papillae, leading to a failure to regenerate. In contrast, over-expressing Fgf10 increases the size of the dermal papillae, expands collar epithelia and mesenchyme, but also prevents feather branch formation and feather keratin differentiation. These results suggest that coordinated Sprouty/FGF pathway activity at different stages is important to modulate feather epidermal stem cells to form distinct feather morphologies along the proximal-distal feather axis. PMID:23000358

  7. Ejecta emplacement: from distal to proximal

    NASA Astrophysics Data System (ADS)

    Artemieva, N.

    2008-09-01

    Introduction Most part of impact ejecta is deposited ballistically at some distance from a crater, defined by ejection velocity V and ejection angle α: d=v2sinα/g. In case of giant impacts, planetary curvature should be taken into account [1]. Combined with ejecta scaling [2], these relations allow to define ejecta thickness as a function of distance. Ejecta from large craters are deposited at velocity high enough to mobilize substrate material and to thicken ejecta deposits [3]. Ballistic approximation is valid for airless bodies (if impact vaporization is not vast) or for proximal ejecta of large impact craters, where ejecta mass per unit area is substantially greater than the mass of involved vapor/atmosphere (M-ratio). Deposition of distal ejecta, in which ejecta mass is negligible compared to the atmosphere, may be also treated in a simplified manner, i.e. as 1) passive motion of ejected particles within an impact plume and 2) later, as sedimentation of particles in undisturbed atmosphere (equilibrium between gravity and drag). In all intermediate M-ratio values, impact ejecta move like a surge, i.e. dilute suspension current in which particles are carried in turbulent flows under the influence of gravity. Surges are well-known for near-surface explosive tests, described in detail for volcanic explosions (Plinian column collapse, phreato-magmatic eruption, lateral blast), and found in ejecta from the Chicxulub [4] and the Ries [5]. Important aspects of surge transport include its ability to deposit ejecta over a larger area than that typical of continuous ballistic ejecta and to create multiple ejecta layers. Numerical model Two-phase hydrodynamics. Surges should be modeled in the frame of two-phase hydrodynamics, i.e. interaction between solid/molten particles and atmospheric gas/impact vapor should be taken into account. There are two techniques of solving equations for dust particle motion in a gas flow. The first one describes solid/molten particles as a

  8. Proximal Femoral Nail Antirotation in Treatment of Fractures of Proximal Femur

    PubMed Central

    Sadic, Sahmir; Custovic, Svemir; Jasarevic, Mahir; Fazlic, Mirsad; Smajic, Nedim; Hrustic, Asmir; Vujadinovic, Aleksandar; Krupic, Ferid

    2014-01-01

    Introduction: Fractures of the proximal femur and hip are relatively common injuries in adults and common source of morbidity and mortality among the elderly. Many methods have been recommended for the treatment of intertrochanteric fractures. Material and methods: We retrospective analyzed all the patients with fractures of the hip treated with proximal femoral nail antirotation (PFNA) at the Clinic of Orthopedic and Traumatology, University Clinical Centre Tuzla from the first of January 2012 to 31 December 2012 years. The study included 63 patients averaged 73.6±11.9 years (range, 29 to 88 years). Fracture type was classified as intertrochanteric (Arbeitsgemeinschaft für Osteosynthesefragen classification 31.A.1, A.2 and A.3) and subtrochanteric fractures (Seinsheimer classification). Results and discussion: The ratio between the genders female-male was 1.6:1. There was statistically significant difference prevalence of female compared to male patients (p=0.012). There were 31 left and 32 right hip fractured. Low energy trauma was the cause of fractures in 57(90.5%) patients. Averaged waiting time for hospitalization was 3.2±7.5 days (range, 0 to 32 days). 44 patients were admitted the same day upon injuring. The average waiting time for the treatment was 3.6±5.7 days. The ratio between with or without co-existent disease was 4.7:1. During the three months postoperatively with ASA score 3 and 4 six patients died. There were no significant differences in deaths from ASA score 1 and 2 (p=0.52). Reoperation for the treatment of implant or fracture-related complications was required in three (4.7%) patients (infection, reimplantation and extraction). Three patient developed deep vein thrombosis. Statistically significant difference was found in the deaths in the first three months compared to the next three months (p=0.02). We found statistically significant difference between pre-injury and postoperative mobility score (p=0.0001). Conclusion: PFNA is an

  9. Degradation and transport of AVP by proximal tubule

    SciTech Connect

    Carone, F.A.; Christensen, E.I.; Flouret, G. Univ. of Aarhus )

    1987-12-01

    High-performance liquid chromatography (HPLC) analysis revealed that (3,4,5-{sup 3}H-Phe{sup 3},Arg{sup 8})vasopressin (({sup 3}H)AVP) was not degraded by isolated renal brush-border membranes or by a cortical lysosomal fraction in vitro; however, in the presence of 1 mM reduced glutathione, ({sup 3}H)AVP was degraded by both preparations. Renal cortical homogenates in vitro and luminal peptidases of proximal tubule in vivo degraded ({sup 3}H)AVP and in both instances yielded phenylalanine, hexapeptide AVP 1-6, heptapeptide AVP 1-7, octapeptide AVP 1-8, and two uncharacterized products X and Y. These data suggest that filtered AVP is reduced in the proximal tubule by a reduced glutathione-dependent transhydrogenase and subsequently cleaved to ({sup 3}H)Phe by tubular aminopeptidases. Following microinfusion of ({sup 3}H)AVP into proximal tubules, 15.7% of the label was absorbed. Five and fifteen minutes after infusion of ({sup 3}H)AVP, sequestration of total label in proximal tubules was 4.5 and 2.1%, respectively, and quantitative electron microscope autoradiography revealed accumulation of grains over apical endocytic vacuoles and lysosomes consistent with endocytic uptake and rapid lysosomal degradation of AVP and/or a large metabolite. Thus, enzymatic cleavage of AVP by luminal and lysosomal peptidases in proximal tubules could involve disulfide bond, C-terminal, and N-terminal loci.

  10. Intramedullary nailing of the proximal humerus: evolution, technique, and results.

    PubMed

    Dilisio, Matthew F; Nowinski, Robert J; Hatzidakis, Armodios M; Fehringer, Edward V

    2016-05-01

    Proximal humerus fractures are the third most common fracture in the elderly. Although most fractures can be treated conservatively with acceptable outcomes, certain fracture patterns are at high risk for progression to humeral malunions, nonunions, stiffness, and post-traumatic arthrosis. The goal of antegrade humeral nailing of proximal humerus fractures is to provide stability to a reduced fracture that allows early motion to optimize patient outcomes. Certain technical pearls are pivotal in managing these difficult fractures with nails; these include rotator cuff management, respect of the soft tissues, anatomic tuberosity position, blood supply maintenance, knowledge of the deforming forces on the proximal humerus, fracture reduction, and rehabilitation strategies. Modern proximal humeral nail designs and techniques assist the surgeon in adhering to these principles and have demonstrated promising outcomes. Humeral nail designs have undergone significant innovation during the past 40 years and now can provide stable fixation in the humeral shaft distally as well as improved stability in the head and tuberosity fragments, which were the common site of fixation failure with earlier generation implants. Compared with other fixation strategies, such as locking plate fixation, no compelling evidence exists to suggest one technique over another. The purpose of this review is to describe the history, results, new designs, and techniques that make modern intramedullary nailing of proximal humerus fractures a viable treatment option. PMID:26895601

  11. Ejecta emplacement: from distal to proximal

    NASA Astrophysics Data System (ADS)

    Artemieva, N.

    2008-09-01

    Introduction Most part of impact ejecta is deposited ballistically at some distance from a crater, defined by ejection velocity V and ejection angle α: d=v2sinα/g. In case of giant impacts, planetary curvature should be taken into account [1]. Combined with ejecta scaling [2], these relations allow to define ejecta thickness as a function of distance. Ejecta from large craters are deposited at velocity high enough to mobilize substrate material and to thicken ejecta deposits [3]. Ballistic approximation is valid for airless bodies (if impact vaporization is not vast) or for proximal ejecta of large impact craters, where ejecta mass per unit area is substantially greater than the mass of involved vapor/atmosphere (M-ratio). Deposition of distal ejecta, in which ejecta mass is negligible compared to the atmosphere, may be also treated in a simplified manner, i.e. as 1) passive motion of ejected particles within an impact plume and 2) later, as sedimentation of particles in undisturbed atmosphere (equilibrium between gravity and drag). In all intermediate M-ratio values, impact ejecta move like a surge, i.e. dilute suspension current in which particles are carried in turbulent flows under the influence of gravity. Surges are well-known for near-surface explosive tests, described in detail for volcanic explosions (Plinian column collapse, phreato-magmatic eruption, lateral blast), and found in ejecta from the Chicxulub [4] and the Ries [5]. Important aspects of surge transport include its ability to deposit ejecta over a larger area than that typical of continuous ballistic ejecta and to create multiple ejecta layers. Numerical model Two-phase hydrodynamics. Surges should be modeled in the frame of two-phase hydrodynamics, i.e. interaction between solid/molten particles and atmospheric gas/impact vapor should be taken into account. There are two techniques of solving equations for dust particle motion in a gas flow. The first one describes solid/molten particles as a

  12. Proximal junctional kyphosis and failure-diagnosis, prevention, and treatment.

    PubMed

    Nguyen, Ngoc-Lam M; Kong, Christopher Y; Hart, Robert A

    2016-09-01

    Technical advancements have enabled the spinal deformity surgeon to correct severe spinal mal-alignment. However, proximal adjacent segment pathology (ASP) remains a significant issue. Examples include proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). Agreement on the definition, classification, and pathophysiology of PJK and PJF remains incomplete, and an understanding of the risk factors, means of prevention, and treatment of this problem remains to be elucidated. In general, PJK is a relatively asymptomatic radiographic diagnosis managed with patient reassurance and monitoring. On the other hand, PJF is characterized by mechanical instability, pain, and more severe kyphosis, with potential for neurologic compromise. Patients who develop PJF more often require revision surgery than those with PJK. This chapter will review the current understanding of PJK and PJF. PMID:27278530

  13. Ultrasound in Dual Nerve Impairment after Proximal Radial Nerve Lesion

    PubMed Central

    Lämmer, Alexandra B; Schwab, Stefan; Schramm, Axel

    2015-01-01

    Introduction Sonography in classical nerve entrapment syndromes is an established and validated method. In contrast, few publications highlight lesions of the radial nerve, particularly of the posterior interosseus nerve (PIN). Method Five patients with a radial nerve lesion were investigated by electromyography, nerve conduction velocity and ultrasound. Further normative values of 26 healthy subjects were evaluated. Results Four patients presented a clinical and electrophysiological proximal axonal radial nerve lesion and one patient showed a typical posterior interosseous nerve syndrome (PINS). The patient with PINS presented an enlargement of the PIN anterior to the supinator muscle. However four patients with proximal lesions showed an unexpected significant enlargement of the PIN within the supinator muscle. Conclusion High-resolution sonography is a feasible method to demonstrate the radial nerve including its distal branches. At least in axonal radial nerve lesions, sonography might reveal abnormalities far distant from a primary proximal lesion site clearly distinct from the appearance in classical PINS. PMID:25992766

  14. Common relationships among proximate composition components in fishes

    USGS Publications Warehouse

    Hartman, K.J.; Margraf, F.J.

    2008-01-01

    Relationships between the various body proximate components and dry matter content were examined for five species of fishes, representing anadromous, marine and freshwater species: chum salmon Oncorhynchus keta, Chinook salmon Oncorhynchus tshawytscha, brook trout Salvelinus fontinalis, bluefish Pomatomus saltatrix and striped bass Morone saxatilis. The dry matter content or per cent dry mass of these fishes can be used to reliably predict the per cent composition of the other components. Therefore, with validation it is possible to estimate fat, protein and ash content of fishes from per cent dry mass information, reducing the need for costly and time-consuming laboratory proximate analysis. This approach coupled with new methods of non-lethal estimation of per cent dry mass, such as from bioelectrical impedance analysis, can provide non-destructive measurements of proximate composition of fishes. ?? 2008 The Authors.

  15. Comparison of distal and proximal centralising devices in hip arthroplasty

    PubMed Central

    Bezer, M.; Akgulle, A. H.; Saygi, B.; Kocaoğlu, B.; Guven, O.

    2008-01-01

    Centralising devices were introduced to ensure that the prosthesis is implanted in a neutral position and that a cement mantle of optimal thickness is achieved proximally and distally. A distal centralising device (DCD) is compared with a proximal midshaft centralising device (PCD) to test which one provides a more neutral prosthetic alignment. Thirty consecutive patients undergoing hemiarthroplasties for femoral neck fractures were studied prospectively. Patients were blindly randomised to receive either a femoral component with proximal midshaft centraliser or distal centraliser. Both components were implanted following the manufacturer’s protocol. Postoperative true anteroposterior and lateral radiographs were made to assess the stem position. There was no statistically significant difference between the two groups in zones 1, 2, 3, 4, 5, 6 and 7 in both anteroposterior and lateral radiographic measurements. DCP and PCD both have similar centralisation and cement mantle. Future studies should be done to evaluate their long-term effect. PMID:18712387

  16. High-throughput determination of RNA structure by proximity ligation.

    PubMed

    Ramani, Vijay; Qiu, Ruolan; Shendure, Jay

    2015-09-01

    We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA proximity ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures. PMID:26237516

  17. Accelerated reabsorption in the proximal tubule produced by volume depletion

    PubMed Central

    Weiner, Michael W.; Weinman, Edward J.; Kashgarian, Michael; Hayslett, John P.

    1971-01-01

    The renal response to chronic depletion of extracellular volume was examined using the techniques of micropuncture. Depletion of salt and water was produced by administration of furosemide to rats maintained on a sodium-free diet. There was a marked fall in body weight, plasma volume, and glomerular filtration rate. The intrinsic reabsorptive capacity of the proximal tubule, measured by the split-droplet technique, was greatly enhanced. The acceleration of proximal fluid reabsorption could not be accounted for by changes in filtration rate, tubular geometry, or aldosterone secretion. The half-time of droplet reabsorption in the distal tubule was not altered by sodium depletion. An increase in the reabsorption of fluid in the proximal tubule, as demonstrated directly in the present experiments, provides an explanation for a variety of clinical phenomena associated with volume depletion. Images PMID:5090054

  18. Graphical Representation of Proximity Measures for Multidimensional Data

    PubMed Central

    Zand, Martin S.; Wang, Jiong; Hilchey, Shannon

    2015-01-01

    We describe the use of classical and metric multidimensional scaling methods for graphical representation of the proximity between collections of data consisting of cases characterized by multidimensional attributes. These methods can preserve metric differences between cases, while allowing for dimensional reduction and projection to two or three dimensions ideal for data exploration. We demonstrate these methods with three datasets for: (i) the immunological similarity of influenza proteins measured by a multidimensional assay; (ii) influenza protein sequence similarity; and (iii) reconstruction of airport-relative locations from paired proximity measurements. These examples highlight the use of proximity matrices, eigenvalues, eigenvectors, and linear and nonlinear mappings using numerical minimization methods. Some considerations and caveats for each method are also discussed, and compact Mathematica programs are provided. PMID:26692757

  19. A Combined Method to Compute the Proximities of Asteroids

    NASA Astrophysics Data System (ADS)

    Šegan, S.; Milisavljević, S.; Marčeta, D.

    2011-09-01

    We describe a simple and efficient numerical-analytical method to find all of the proximities and critical points of the distance function in the case of two elliptical orbits with a common focus. Our method is based on the solutions of Simovljević's (1974) graphical method and on the transcendent equations developed by Lazović (1993). The method is tested on 2 997 576 pairs of asteroid orbits and compared with the algebraic and polynomial solutions of Gronchi (2005). The model with four proximities was obtained by Gronchi (2002) only by applying the method of random samples, i.e., after many simulations and trials with various values of elliptical elements. We found real pairs with four proximities.

  20. A Flexible Proximity Sensor Fully Fabricated by Inkjet Printing

    PubMed Central

    Wang, Chin-Tsan; Huang, Kuo-Yi; Lin, David T. W.; Liao, Wei-Chia; Lin, Hua-Wei; Hu, Yuh-Chung

    2010-01-01

    A flexible proximity sensor fully fabricated by inkjet printing is proposed in this paper. The flexible proximity sensor is composed of a ZnO layer sandwiched in between a flexible aluminum sheet and a web-shaped top electrode layer. The flexible aluminum sheet serves as the bottom electrode. The material of the top electrode layer is nano silver. Both the ZnO and top electrode layers are deposited by inkjet printing. The fully inkjet printing process possesses the advantages of direct patterning and low-cost. It does not require photolithography and etching processes since the pattern is directly printed on the flexible aluminum sheet. The prototype demonstrates that the presented flexible sensor is sensitive to the human body. It may be applied to proximity sensing or thermal eradiation sensing. PMID:22399923

  1. High-throughput determination of RNA structure by proximity ligation

    PubMed Central

    Ramani, Vijay; Qiu, Ruolan; Shendure, Jay

    2015-01-01

    We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA Proximity Ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle, and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures. PMID:26237516

  2. Proximal femoral reconstruction with a constrained acetabulum in oncologic patients.

    PubMed

    Jawad, Muhammad Umar; Brien, Earl W

    2014-02-01

    Metallic endoprostheses are used for oncological reconstruction around the proximal femur and hip joint. Common modes of failure with hemiarthroplasty or standard hip arthroplasty after proximal femoral replacement include dislocation, late hip pain, and infection. The authors reviewed hospital records to identify patients undergoing constrained tripolar hip arthroplasty for oncological reasons between 2002 and 2012. Inclusion criterion was at least 12-cm proximal femoral resection, including patients with total femur reconstruction. A total of 33 patients were reviewed. Information regarding demographics, length of follow-up, treatment characteristics, and patient outcomes was extracted. Average follow-up for all patients was 912.33 days (30.4 months). Average follow-up was 1396.1 days for living patients and 428.6 days for deceased patients. Average estimated blood loss was 462.12 cc: an average of 1080 cc for patients undergoing total femoral resection and replacement and 315.8 cc for patients undergoing proximal femoral resection and replacement. Average operative time was 137.7 minutes: an average of 205 minutes for patients undergoing total femoral resection and replacement and 119.1 minutes for patients undergoing proximal femoral resection and replacement. Average Musculoskeletal Tumor Society score was 21.7. There were no dislocations in the cohort. A constrained tripolar device can be safely used for oncological proximal femoral reconstructions while minimizing the risk of dislocation. Positioning of the acetabular implant in neutral anatomic version in conjunction with a neutral-placed femoral component provides the greatest range of motion, reduction of liner impingement, and improved hip stability. PMID:24679207

  3. Proximity Operations Nano-Satellite Flight Demonstration (PONSFD) Rendezvous Proximity Operations Design and Trade Studies

    NASA Astrophysics Data System (ADS)

    Griesbach, J.; Westphal, J. J.; Roscoe, C.; Hawes, D. R.; Carrico, J. P.

    2013-09-01

    The Proximity Operations Nano-Satellite Flight Demonstration (PONSFD) program is to demonstrate rendezvous proximity operations (RPO), formation flying, and docking with a pair of 3U CubeSats. The program is sponsored by NASA Ames via the Office of the Chief Technologist (OCT) in support of its Small Spacecraft Technology Program (SSTP). The goal of the mission is to demonstrate complex RPO and docking operations with a pair of low-cost 3U CubeSat satellites using passive navigation sensors. The program encompasses the entire system evolution including system design, acquisition, satellite construction, launch, mission operations, and final disposal. The satellite is scheduled for launch in Fall 2015 with a 1-year mission lifetime. This paper provides a brief mission overview but will then focus on the current design and driving trade study results for the RPO mission specific processor and relevant ground software. The current design involves multiple on-board processors, each specifically tasked with providing mission critical capabilities. These capabilities range from attitude determination and control to image processing. The RPO system processor is responsible for absolute and relative navigation, maneuver planning, attitude commanding, and abort monitoring for mission safety. A low power processor running a Linux operating system has been selected for implementation. Navigation is one of the RPO processor's key tasks. This entails processing data obtained from the on-board GPS unit as well as the on-board imaging sensors. To do this, Kalman filters will be hosted on the processor to ingest and process measurements for maintenance of position and velocity estimates with associated uncertainties. While each satellite carries a GPS unit, it will be used sparsely to conserve power. As such, absolute navigation will mainly consist of propagating past known states, and relative navigation will be considered to be of greater importance. For relative observations

  4. High resolution fabrication of nanostructures using controlled proximity nanostencil lithography

    NASA Astrophysics Data System (ADS)

    Jain, T.; Aernecke, M.; Liberman, V.; Karnik, R.

    2014-02-01

    Nanostencil lithography has a number of distinct benefits that make it an attractive nanofabrication processes, but the inability to fabricate features with nanometer precision has significantly limited its utility. In this paper, we describe a nanostencil lithography process that provides sub-15 nm resolution even for 40-nm thick structures by using a sacrificial layer to control the proximity between the stencil and substrate, thereby enhancing the correspondence between nanostencil patterns and fabricated nanostructures. We anticipate that controlled proximity nanostencil lithography will provide an environmentally stable, clean, and positive-tone candidate for fabrication of nanostructures with high resolution.

  5. Lateral Casimir force beyond the proximity-force approximation.

    PubMed

    Rodrigues, Robson B; Neto, Paulo A Maia; Lambrecht, Astrid; Reynaud, Serge

    2006-03-17

    We argue that the appropriate variable to study a nontrivial geometry dependence of the Casimir force is the lateral component of the Casimir force, which we evaluate between two corrugated metallic plates outside the validity of the proximity-force approximation. The metallic plates are described by the plasma model, with arbitrary values for the plasma wavelength, the plate separation, and the corrugation period, the corrugation amplitude remaining the smallest length scale. Our analysis shows that in realistic experimental situations the proximity-force approximation overestimates the force by up to 30%. PMID:16605712

  6. Proximal antecedents to violent events in adolescent dating relationships.

    PubMed

    Stephenson, Pamela S; Martsolf, Donna S; Draucker, Claire Burke

    2011-01-01

    Dating violence affects 25-60% of adolescents. This study developed a typology of proximal antecedents to violent events in adolescent dating relationships. Descriptions of 307 dating violence events were extracted from transcribed interviews with 87 young adults who experienced dating violence as adolescents. Verbatim text preceding the description of each violent event was identified as a proximal antecedent. Cross-case analysis was used to develop a typology of five antecedent categories: "pulling away,"  "demanding obedience," "discovering involvement with a rival," "defining the relationship," "demonstrating disrespect." Practitioners can use this typology to engage teens in discussions of factors that precede dating violence events. PMID:21992258

  7. Investigation of proximity effects in electron microscopy and lithography

    SciTech Connect

    Walz, M.-M.; Vollnhals, F.; Rietzler, F.; Schirmer, M.; Steinrueck, H.-P.; Marbach, H.

    2012-01-30

    A fundamental challenge in lithographic and microscopic techniques employing focused electron beams are so-called proximity effects due to unintended electron emission and scattering in the sample. Herein, we apply a method that allows for visualizing electron induced surface modifications on a SiN substrate covered with a thin native oxide layer by means of iron deposits. Conventional wisdom holds that by using thin membranes proximity effects can be effectively reduced. We demonstrate that, contrary to the expectation, these can be indeed larger on a 200 nm SiN-membrane than on the respective bulk substrate due to charging effects.

  8. Inverse Proximity Effect in Superconductor-ferromagnet Bilayer Structures

    SciTech Connect

    Xia, Jing

    2010-04-05

    Measurements of the polar Kerr effect using a zero-area-loop Sagnac magnetometer on Pb/Ni and Al/(Co-Pd) proximity-effect bilayers show unambiguous evidence for the 'inverse proximity effect,' in which the ferromagnet (F) induces a finite magnetization in the superconducting (S) layer. To avoid probing the magnetic effects in the ferromagnet, the superconducting layer was prepared much thicker than the light's optical penetration depth. The sign and size of the effect, as well as its temperature dependence agree with recent predictions by Bergeret et al.[1].

  9. Technique, indications, and results of proximal medial gastrocnemius lengthening.

    PubMed

    Barouk, Pierre

    2014-12-01

    Gastrocnemius proximal lengthening was first performed to correct spasticity in children, and was adapted for the patient with no neuromuscular condition in the late 1990s. Since then, the proximal gastrocnemius release has become less invasive and has evolved to include only the fascia overlying the medial head of the gastrocnemius muscle. The indications for performing this procedure are a clinically demonstrable gastrocnemius contracture that influences a variety of clinical conditions in the forefoot, hindfoot, and ankle. It is a safe and easy procedure that can be performed bilaterally simultaneously, and does not require immobilization of the ankle after surgery. PMID:25456723

  10. Driving change: kidney proximal tubule CSF-1 polarizes macrophages

    PubMed Central

    Perry, Heather M.; Okusa, Mark D.

    2016-01-01

    Macrophage colony-stimulating factor (CSF-1 or M-CSF) is important for kidney repair after acute kidney injury (AKI). CSF-1 is upregulated in tubule epithelial cells in response to kidney injury stimuli and binds to its sole receptor, CSF1R, in an autocrine and paracrine manner. Wang and colleagues used a genetic approach to constitutively delete Csf1 in proximal tubules to establish that proximal tubule production of CSF-1 is important for polarizing and skewing macrophages toward an M2 phenotype, and for recovery from AKI. PMID:26649657

  11. Superconductor disorder and strong proximity coupling effects in Majorana nanowires

    NASA Astrophysics Data System (ADS)

    Cole, William; Sau, Jay

    Topological superconductivity induced by proximity to a conventional superconductor is only robust against moderate disorder in the parent superconductor, and only when the energy scale of the interface coupling is much smaller than the parent gap. I present detailed calculations of proximity-induced superconductivity in one-dimensional, spin-orbit coupled, semiconductor nanowires when the parent superconductor disorder and interface coupling exceed this limit. This parameter regime is characterized by unique spectroscopic signatures on both sides of the external field tuned topological phase transition. This work is supported by LPS-MPO-CMTC, Microsoft Q, and JQI-NSF-PFC.

  12. Ectrodactyly and proximal/intermediate interstitial deletion 7q

    SciTech Connect

    McElveen, C.; Carvajal, M.V.; Moscatello, D.

    1995-03-13

    We report on an individual with severe mental retardation, seizures, microcephaly, unusual face, scoliosis, and cleft feet and cleft right hand. The chromosomal study showed a proximal interstitial deletion 7q (q11.23q22). From our review of the literature, 11 patients have been reported with ectrodactyly (split hand/split foot malformation) and proximal/intermediate interstitial deletions or rearrangements of 7q. The critical segment for ectrodactyly seems to be located between 7q21.2 and 7q22.1. This malformation is present in 41% of the patients whose deletion involves the critical segment. 37 refs., 3 figs., 1 tab.

  13. Double-driven shield capacitive type proximity sensor

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    1993-01-01

    A capacity type proximity sensor comprised of a capacitance type sensor, a capacitance type reference, and two independent and mutually opposing driven shields respectively adjacent to the sensor and reference and which are coupled in an electrical bridge circuit configuration and driven by a single frequency crystal controlled oscillator is presented. The bridge circuit additionally includes a pair of fixed electrical impedance elements which form adjacent arms of the bridge and which comprise either a pair of precision resistances or capacitors. Detection of bridge unbalance provides an indication of the mutual proximity between an object and the sensor. Drift compensation is also utilized to improve performance and thus increase sensor range and sensitivity.

  14. Arthroscopic Surgical Techniques for the Management of Proximal Biceps Injuries.

    PubMed

    Werner, Brian C; Holzgrefe, Russell E; Brockmeier, Stephen F

    2016-01-01

    Current arthroscopic surgical techniques for the management of proximal biceps tendon disorders encompass 3 commonly advocated procedures: proximal biceps anchor reattachment (superior labrum anterior to posterior or SLAP repair), biceps tenotomy, and arthroscopic biceps tenodesis. The indications for each procedure vary based on injury pattern, symptomatic presentation, concomitant pathologic abnormality, and most notably, patient factors, such as age, functional demand, and specific sport or activity participation. Outcomes after SLAP repair are generally favorable, although recent studies have found biceps tenodesis to be the preferred treatment for certain patient populations. PMID:26614472

  15. Proximal Femoral Nail Antirotation Versus Reverse Less Invasive Stabilization System-distal Femur for Treating Proximal Femoral Fractures

    PubMed Central

    Jiang, Xuan; Wang, Ying; Ma, XinLong; Ma, JianXiong; Wang, Chen; Zhang, ChengBao; Han, Zhe; Sun, Lei; Lu, Bin

    2016-01-01

    Abstract The aim of this study was to compare the effectiveness and safety of 2 surgical techniques that are used to treat proximal femoral fractures. A systematic literature search (up to December 2014) was conducted in Medline, Embase, PubMed, and The Cochrane Central Register of Controlled Trials to screen for studies comparing proximal femoral nail antirotation (PFNA) with less invasive stabilization system–distal femur (LISS-DF) for proximal femoral fractures. Two authors independently assessed the methodological quality of the included studies and extracted data. Surgical information and postoperative outcomes were analyzed. A total of 7 studies with 361 patients who satisfied the eligibility criteria included 3 randomized controlled trials and 4 case-controlled trials associated with PFNA versus LISS in treating proximal femoral fractures. Our results demonstrated that there was a significant reduction in hospital stay and time to weight-bearing ambulation and bone healing for PFNA compared with LISS (odds ratio [OR] −1.48, 95% confidence interval [CI] −2.92 to −0.05; OR −7.08, 95% CI −8.32 to −5.84; OR −2.71, 95% CI −4.76 to 0.67). No statistically significant difference was observed between the 2 groups for operative time, blood loss volume, Harris hip score, and incidence of complications. Based on the results of this analysis, we inferred that PFNA is safer and more effective than reverse LISS-DF in patients undergoing osteosynthesis for proximal femoral fractures, and that PFNA is associated with reduced hospital stays and reduced time to weight-bearing ambulation and bone healing. Nonetheless, in certain cases in which PFNA is not suitable due to abnormal structure of the proximal femur or particularly unstable fractures, the LISS plate technique could be a useful alternative. PMID:27057840

  16. Longitudinal effects of contextual and proximal factors on mother-infant interactions among Brazilian adolescent mothers.

    PubMed

    Diniz, Eva; DeSousa, Diogo; Koller, Silvia H; Volling, Brenda L

    2016-05-01

    Adolescent mothers often come from vulnerable backgrounds which might impact the quality of both maternal and infant behavior. Despite the negative impact of adolescent motherhood for maternal and infant behavior, social support may decrease the risks and promote maternal behavior toward the infant. The aim of this study was to investigate longitudinally the effects of proximal (maternal behavior) and distal (mother's perceived social support) variables on infant development in a sample of Brazilian adolescent mothers and their infants. Thirty-nine adolescent mothers (Mage=17.26years; SD=1.71) were observed interacting with their infants at 3 and 6 months postpartum and reported on social support. Results revealed that maternal and infant behavior were associated within and across times. Mothers' perceived social support at 3 months had an indirect effect on infant behavior at 6 months, totally mediated by maternal behavior at 6 months. Our findings revealed the mutual influence between maternal and infant behavior, revealing a proximal process. The results also underscored the importance of the passage of time in the interplay between mother-infant interactions and their developmental context. PMID:27110652

  17. Proximal disruptor aided ligation (ProDAL) of kilobase-long RNAs.

    PubMed

    Zhovmer, Alexander; Qu, Xiaohui

    2016-07-01

    RNA with site-specific modification is a useful tool for RNA biology studies. However, generating kilobase (kb) -long RNA with internal modification at a site distant from RNA termini remains challenging. Here we report an enhanced splint ligation technique, proximal disruptor aided ligation (ProDAL), which allows adequate efficiency toward this purpose. The key to our approach is using multiple DNA oligonucleotides, 'proximal disruptors', to target the RNA substrate sequence next to the ligation site. The binding of disruptors helps to free the ligation site from intramolecular RNA basepairing, and consequently promotes more efficient formation of the pre-ligation complex and a higher overall ligation yield. We used naturally occurring 1.0 kb renilla and 1.9 kb firefly luciferase mRNA sequences to test the efficacy of our approach. ProDAL yielded 9-14% efficiency for the ligation between two RNA substrates, both of which were between 414 and 1313 nucleotides (nt) long. ProDAL also allowed similarly high efficiency for generating kb-long RNA with site-specific internal modification by a simple three-part ligation between two long RNA substrates and a modification-carrying RNA oligonucleotide. In comparison, classical splint ligation yielded a significantly lower efficiency of 0-2% in all cases. We expect that ProDAL will benefit studies involving kb-long RNAs, including translation, long non-coding RNAs, RNA splicing and modification, and large ribonucleoprotein complexes. PMID:27211284

  18. Invigoration of reward-seeking by cue and proximity encoding in the nucleus accumbens

    PubMed Central

    McGinty, Vincent B.; Lardeux, Sylvie; Taha, Sharif A.; Kim, James J.; Nicola, Saleem M.

    2014-01-01

    Summary A key function of the nucleus accumbens is to promote vigorous reward-seeking, but the corresponding neural mechanism has not been identified despite many years of research. Here we study cued flexible approach behavior, a form of reward-seeking that strongly depends on the accumbens, and we describe a robust, single-cell neural correlate of behavioral vigor in the excitatory response of accumbens neurons to reward-predictive cues. Well before locomotion begins, this cue-evoked excitation predicts both the movement initiation latency and speed of subsequent flexible approach responses, but not of stereotyped, inflexible responses. Moreover, the excitation simultaneously signals the subject’s proximity to the approach target, a signal that appears to mediate greater response vigor on trials that begin with the subject closer to the target. These results demonstrate a neural mechanism for response invigoration whereby accumbens neuronal encoding of reward availability and target proximity together drive the onset and speed of reward-seeking locomotion. PMID:23764290

  19. On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry

    PubMed Central

    2016-01-01

    Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is “tethering”—a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein–protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: “multifunctional scaffolding” versus “on-demand targeting”. By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms. PMID:26907082

  20. Proximity biotinylation provides insight into the molecular composition of focal adhesions at the nanometer scale.

    PubMed

    Dong, Jing-Ming; Tay, Felicia Pei-Ling; Swa, Hannah Lee-Foon; Gunaratne, Jayantha; Leung, Thomas; Burke, Brian; Manser, Ed

    2016-01-01

    Focal adhesions are protein complexes that link metazoan cells to the extracellular matrix through the integrin family of transmembrane proteins. Integrins recruit many proteins to these complexes, referred to as the "adhesome." We used proximity-dependent biotinylation (BioID) in U2OS osteosarcoma cells to label proteins within 15 to 25 nm of paxillin, a cytoplasmic focal adhesion protein, and kindlin-2, which directly binds β integrins. Using mass spectrometry analysis of the biotinylated proteins, we identified 27 known adhesome proteins and 8 previously unknown components close to paxillin. However, only seven of these proteins interacted directly with paxillin, one of which was the adaptor protein Kank2. The proteins in proximity to β integrin included 15 of the adhesion proteins identified in the paxillin BioID data set. BioID also correctly established kindlin-2 as a cell-cell junction protein. By focusing on this smaller data set, new partners for kindlin-2 were found, namely, the endocytosis-promoting proteins liprin β1 and EFR3A, but, contrary to previous reports, not the filamin-binding protein migfilin. A model adhesome based on both data sets suggests that focal adhesions contain fewer components than previously suspected and that paxillin lies away from the plasma membrane. These data not only illustrate the power of using BioID and stable isotope-labeled mass spectrometry to define macromolecular complexes but also enable the correct identification of therapeutic targets within the adhesome. PMID:27303058

  1. Engineering Promoter Architecture in Oleaginous Yeast Yarrowia lipolytica.

    PubMed

    Shabbir Hussain, Murtaza; Gambill, Lauren; Smith, Spencer; Blenner, Mark A

    2016-03-18

    Eukaryotic promoters have a complex architecture to control both the strength and timing of gene transcription spanning up to thousands of bases from the initiation site. This complexity makes rational fine-tuning of promoters in fungi difficult to predict; however, this very same complexity enables multiple possible strategies for engineering promoter strength. Here, we studied promoter architecture in the oleaginous yeast, Yarrowia lipolytica. While recent studies have focused on upstream activating sequences, we systematically examined various components common in fungal promoters. Here, we examine several promoter components including upstream activating sequences, proximal promoter sequences, core promoters, and the TATA box in autonomously replicating expression plasmids and integrated into the genome. Our findings show that promoter strength can be fine-tuned through the engineering of the TATA box sequence, core promoter, and upstream activating sequences. Additionally, we identified a previously unreported oleic acid responsive transcription enhancement in the XPR2 upstream activating sequences, which illustrates the complexity of fungal promoters. The promoters engineered here provide new genetic tools for metabolic engineering in Y. lipolytica and provide promoter engineering strategies that may be useful in engineering other non-model fungal systems. PMID:26635071

  2. The theoretical simulation on electrostatic distribution of 1st proximity region in proximity focusing low-light-level image intensifier

    NASA Astrophysics Data System (ADS)

    Zhang, Liandong; Bai, Xiaofeng; Song, De; Fu, Shencheng; Li, Ye; Duanmu, Qingduo

    2015-03-01

    Low-light-level night vision technology is magnifying low light level signal large enough to be seen by naked eye, which uses the photons - photoelectron as information carrier. Until the micro-channel plate was invented, it has been possibility for the realization of high performance and miniaturization of low-light-level night vision device. The device is double-proximity focusing low-light-level image intensifier which places a micro-channel plate close to photocathode and phosphor screen. The advantages of proximity focusing low-light-level night vision are small size, light weight, small power consumption, no distortion, fast response speed, wide dynamic range and so on. It is placed parallel to each other for Micro-channel plate (both sides of it with metal electrode), the photocathode and the phosphor screen are placed parallel to each other. The voltage is applied between photocathode and the input of micro-channel plate when image intensifier works. The emission electron excited by photo on the photocathode move towards to micro-channel plate under the electric field in 1st proximity focusing region, and then it is multiplied through the micro-channel. The movement locus of emission electrons can be calculated and simulated when the distributions of electrostatic field equipotential lines are determined in the 1st proximity focusing region. Furthermore the resolution of image tube can be determined. However the distributions of electrostatic fields and equipotential lines are complex due to a lot of micro-channel existing in the micro channel plate. This paper simulates electrostatic distribution of 1st proximity region in double-proximity focusing low-light-level image intensifier with the finite element simulation analysis software Ansoft maxwell 3D. The electrostatic field distributions of 1st proximity region are compared when the micro-channel plates' pore size, spacing and inclination angle ranged. We believe that the electron beam movement

  3. 75 FR 33198 - Co-Location/Proximity Hosting Services

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ...The Commodity Futures Trading Commission (``CFTC'' or ``Commission'') proposes a rule (``Proposal'') that requires Designated Contract Markets (DCMs), Derivatives Transaction Execution Facilities (DTEFs), and Exempt Commercial Markets (ECMs) that list significant price discovery contracts (SPDCs) that offer co-location and/or proximity hosting services to market participants to have equal......

  4. Proximal versus Distal Validity Coefficients for Teacher Observational Instruments

    ERIC Educational Resources Information Center

    Marzano, Robert J.

    2014-01-01

    This study examined the use of measures of student learning computed using end-of-year assessments (distal measures) versus measures of student learning associated with a single lesson (proximal measures) as criterion scores for the validity of observations of teachers' pedagogical skills. The validity coefficients computed using distal…

  5. Sharpening a Tool for Teaching: The Zone of Proximal Development

    ERIC Educational Resources Information Center

    Wass, Rob; Golding, Clinton

    2014-01-01

    Vygotsky's Zone of Proximal Development (ZPD) provides an important understanding of learning, but its implications for teachers are often unclear or limited and could be further explored. We use conceptual analysis to sharpen the ZPD as a teaching tool, illustrated with examples from teaching critical thinking in zoology. Our conclusions are…

  6. Scaffolding Critical Thinking in the Zone of Proximal Development

    ERIC Educational Resources Information Center

    Wass, Rob; Harland, Tony; Mercer, Alison

    2011-01-01

    This paper explores student experiences of learning to think critically. Twenty-six zoology undergraduates took part in the study for three years of their degree at the University of Otago, New Zealand. Vygotsky's developmental model of the Zone of Proximal Development (ZPD) provided a framework as we examined how critical thinking was developed.…

  7. Proximity induced exchange interaction in graphene-YIG devices

    NASA Astrophysics Data System (ADS)

    Leutenantsmeyer, Johannes Christian; Kaverzin, Alexey; Wojtaszek, Magdalena; van Wees, Bart J.; Physics of Nanodevices Team

    The proximity of two materials with radically different properties can give rise to a new physical phenomenon present only in the direct vicinity to the interface. Graphene is a perfect candidate for observing proximity effects as being ultimately thin and therefore ultimately sensitive for such interactions. Ferromagnetism is one of the desired properties for spintronics applications of graphene. It is absent in the pristine state, however, one can artificially induce magnetic ordering by bringing graphene in the proximity of ferrimagnetic insulating material, such as yttrium iron garnet (YIG). In this work we show that a monolayer of graphene placed on top of YIG adopts the exchange interaction induced by YIG and thus becomes ferromagnetic even at room temperatures. The proximity induced exchange interaction results in an effective magnetic field that influences directly the spin transport in graphene seen in a spin precession measurements. We are able to fit the measured Hanle dependences with extended solutions of Bloch diffusion equations and extract the value of the effective exchange field that is around 200 mT. Our findings open up a new route for creating novel all graphene in plane spin valve devices for spintronics applications. European Union's Seventh Framework Programme n607904-13 Spinograph, n604391 Graphene Flagship, FOM, ZIAM.

  8. Stationary Properties of High Critical Temperature Proximity Effect Josephson Junctions

    NASA Technical Reports Server (NTRS)

    Delin, K. A.; Kleinsasser, A. W.

    1995-01-01

    The data is reviewed about superconductor-normal-superconductor (SNS) devices, and the conclusion is drawn that there is no conventional proximity effect in the majority of reported high Tc devices. The present experimental and theoretical understanding of SNS junctions is discussed as well as implications for future research.

  9. Proximity Effect at Graphene - High Tc Superconductor Junctions

    NASA Astrophysics Data System (ADS)

    Wang, Da; Shih, En-Min; Arefe, Ghidewon; Kim, Youngduck; Edelberg, Drew; Andrade, Erick; Wang, Dennis; Hone, James; Dean, Cory; Pasupathy, Abhay; Department of Physics, Columbia University, New York, NY 10027, USA Collaboration

    The proximity effect is a well-known mesoscopic phenomenon where Cooper pairs from a superconductor (S) enter into a normal metal (N) that is well coupled to it. Since graphene was discovered a decade ago, the proximity effect at superconductor-graphene junctions has been extensively studied and interesting phenomena such as specular Andreev reflection and ballistic transport at graphene Josephson junctions have been observed. However, superconductors used in these experiments to date are of conventional low Tc, such as aluminum(Tc=1.2K), NbSe2(Tc=7K), and MoRe(Tc=8K). Understanding how the proximity effect works between high-Tc superconductors (pnictides and cuprates) and the Dirac Fermions of graphene remains largely unexplored. The chief technical challenge here is to create high-quality junctions between high-Tc superconductors and graphene. In this work, we will introduce a home-made setup that allows us to exfoliate, transfer and encapsulate superconductor-graphene junctions in a well controlled inert atmosphere. Transport measurements of the proximity effect at graphene-iron pnictide(FeSe, FeTeSe) and graphene-cuprate(BSCCO) junctions will be described.

  10. Bridging Pedagogies: Drama, Multiliteracies, and the Zone of Proximal Development

    ERIC Educational Resources Information Center

    Macy, Leonora

    2016-01-01

    This article examines how one educator embraced Vygotsky's concept of the zone of proximal development (ZPD) while using drama to scaffold learning about Dr. Seuss's "The Lorax" for first-grade students. This learning event is interpreted with reference to the ZPD and the New London Group's pedagogy of multiliteracies. The author asserts…

  11. Reflections on the Ecolab and the Zone of Proximal Development

    ERIC Educational Resources Information Center

    Luckin, Rosemary; du Boulay, Benedict

    2016-01-01

    In 1999 we reported a study that explored the way that Vygotsky's Zone of Proximal Development could be used to inform the design of an Interactive Learning Environment called the Ecolab. Two aspects of this work have subsequently been used for further research. Firstly, there is the interpretation of the ZPD and its associated theory that was…

  12. Rendezvous and Proximity Operations of the Space Shuttle

    NASA Technical Reports Server (NTRS)

    Goodman, John L.

    2005-01-01

    Space Shuttle rendezvous missions present unique challenges that were not fully recognized when the Shuttle was designed. Rendezvous targets could be passive (i.e., no lights or transponders), and not designed to facilitate Shuttle rendezvous, proximity operations, and retrieval. Shuttle reaction control system jet plume impingement on target spacecraft presented induced dynamics, structural loading, and contamination concerns. These issues, along with limited reaction control system propellant in the Shuttle nose, drove a change from the legacy Gemini/Apollo coelliptic profile to a stable orbit profile, and the development of new proximity operations techniques. Multiple scientific and on-orbit servicing missions, and crew exchange, assembly and replenishment flights to Mir and to the International Space Station drove further profile and piloting technique changes. These changes included new proximity operations, relative navigation sensors, and new computer generated piloting cues. However, the Shuttle's baseline rendezvous navigation system has not required modification to place the Shuttle at the proximity operations initiation point for all rendezvous missions flown.

  13. Fracture through a geode in the proximal ulna.

    PubMed

    Wordsworth, B P; Mowat, A G; Watson, N A

    1984-05-01

    Chronic joint pain in rheumatoid arthritis may mask that from other causes. Stress fractures, particularly in osteoporotic lower limb bones of such patients, are well described but can still cause diagnostic difficulty. These difficulties were highlighted by a case in which an unusual fracture occurred through a geode in the proximal ulna mimicking an exacerbation of synovitis in the elbow joint. PMID:6722411

  14. Innervation of the renal proximal convoluted tubule of the rat

    SciTech Connect

    Barajas, L.; Powers, K. )

    1989-12-01

    Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries.

  15. Aging and Family Resources: Availability and Proximity of Kin.

    ERIC Educational Resources Information Center

    Hays, Judith A.

    Family resources are vital to older individuals. In order to establish base-line data on the availability and proximity of kin to persons aged 45 or older in a midwestern state, information was gathered for six months from the obituary section of the local newspaper. The sample includeed 1,413 individuals. Information included availabiltiy of kin,…

  16. Performance characteristics of proximity focused ultraviolet image converters

    NASA Technical Reports Server (NTRS)

    Williams, J. T.; Feibelman, W. A.

    1973-01-01

    Performance characteristics of Bendix type BX 8025-4522 proximity focused image tubes for ultraviolet to visible light conversion are presented. Quantum efficiency, resolution, background, geometric distortion, and environmental test results are discussed. The converters use magnesium fluoride input windows with Cs - Te photocathodes, and P-11 phosphors on fiber optic output windows.

  17. Performance characteristics of proximity focused ultraviolet image converters

    NASA Technical Reports Server (NTRS)

    Williams, J. T.; Feibelman, W. A.

    1973-01-01

    Performance characteristics of Bendix type BX 8025-4522 proximity focused image tubes for UV to visible light conversion are presented. Quantum efficiency, resolution, background, geometric distortion, and environmental test results are discussed. The converters use magnesium fluoride input windows with Cs-Te photocathodes and P-11 phosphors on fiber optic output windows.

  18. Proximal tibio-fibular synostosis. A rare congenital anomaly.

    PubMed

    O'Dwyer, K J

    1991-01-01

    A case of proximal tibiofibular synostosis is presented along with a review of the literature. The variety of presenting complaints is discussed and the syndrome is compared with that of radio-ulnar synostosis. Possible modes of treatment are explained. PMID:1872166

  19. Metastatic transitional cell carcinoma in proximal humerus of a dog

    PubMed Central

    Malek, Sarah; Murphy, Kimberly A.; Nykamp, Stephanie G.; Allavena, Rachel

    2011-01-01

    Transitional cell carcinoma (TCC) was diagnosed in the proximal humerus of a dog that was presented with persistent right forelimb lameness with no clinical signs of urinary tract involvement. A diagnosis of TCC was made from surgical biopsy of the humeral lesion with subsequent necropsy revealing the prostatic urethra as the primary site of the tumor. PMID:22379204

  20. Children's Attentional Processing of Mother and Proximity Seeking

    PubMed Central

    2015-01-01

    Attachment expectations regarding the availability of mother as a source for support are supposed to influence distressed children’s support seeking behavior. Because research is needed to better understand the mechanisms related to support seeking behavior, this study tested the hypothesis that the cognitive processing of mother-related information is linked to proximity and support seeking behavior. Uncertainty in maternal support has been shown to be characterized by a biased attentional encoding of mother, reducing the breadth of children’s attentional field around her. We investigated whether this attentional bias is related to how long distressed children wait before seeking their mother’s proximity. Thirty-three children (9-11 years) participated in this study that consisted of experimental tasks to measure attentional breadth and to observe proximity seeking behavior and of questionnaires to measure confidence in maternal support and experienced distress. Results suggested that distressed children with a more narrow attentional field around their mother wait longer to seek her proximity. Key Message: These findings provide a first support for the hypothesis that the attentional processing of mother is related to children’s attachment behavior. PMID:25927921

  1. Conservative Treatment for Bilateral Displaced Proximal Humerus Head Fracture

    PubMed Central

    Velutini-Becker, Ricardo; Aguilar-Alcalá, Luis D

    2016-01-01

    Proximal humerus fracture represents five to eight percent of all fractures and is twice as common in women than in men. Most cases of displaced fracture of the proximal humerus are treated surgically; it is probable that more cases are preferred to be treated surgically greater than required. The optimal treatment for these fractures remains controversial, but physicians have a tendency to treat via open reduction and fixation with angular locking plates or glenohumeral arthroplasty.  We present a case of a 71-year-old woman with bilateral displaced proximal humeral fracture. Conservative treatment was initiated with two hanging casts, achieving radiological reduction on week one. After two additional weeks of casting, treatment continued with radiologic control and home physical therapy, ultimately an excellent functional outcome and adequate radiological reduction was obtained.    Even in bilaterally displaced proximal humerus fractures, conservative treatment can be an efficient option, reducing complications, reaching adequate functional results and acceptable radiographic reduction.​ PMID:27489750

  2. Constructing Proximity: Relating to Readers in Popular and Professional Science

    ERIC Educational Resources Information Center

    Hyland, Ken

    2010-01-01

    The view of academic discourse as a rhetorical activity involving interactions between writers and readers is now central to most perspectives on EAP, but these interactions are conducted differently in different disciplinary and generic contexts. In this paper I use the term "proximity" to refer to a writer's control of those rhetorical features…

  3. Interlanguage Pragmatics in the Zone of Proximal Development

    ERIC Educational Resources Information Center

    Ohta, Amy Snyder

    2005-01-01

    Vygotsky's zone of proximal development (ZPD) has been fruitfully applied in L2 research that examines second and foreign language learning. This paper considers the applicability of the ZPD to interlanguage pragmatics instruction and research. First, the ZPD is defined [Vygotsky, L.S., 1978. Mind in Society: The Development of Higher…

  4. Proximity to coast is linked to climate change belief.

    PubMed

    Milfont, Taciano L; Evans, Laurel; Sibley, Chris G; Ries, Jan; Cunningham, Andrew

    2014-01-01

    Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local. PMID:25047568

  5. [Proximal anastomotic marker use in coronary artery bypass operations].

    PubMed

    Cikirikçioğlu, Mustafa; Ozbay, Gültaç; Duran, Enver

    2002-06-01

    Detection and evaluation of aorto-to-saphenous vein anastomosis sites (proximal anastomoses) in patients who had undergone coronary artery bypass surgery are comparatively harder than native coronary orifices during follow-up re-angiography procedures. Placement of a radioopaque proximal anastomotic graft marker during coronary artery bypass procedure poses medical and economical advantages in case of postoperative re-angiography during follow-up of these patients. Indication of whether or not to use a proximal anastomotic marker is in general decide on by the operating surgeon. However, coronary angiography is a task of interventional cardiologist. Difference of the teams performing catheterization and the surgical procedure may rise some inconsistencies in terms of requirements for these markers. In order for these dilemmas to be prevented, surgical team should be informed of the complication re-angiography procedure. Proper strategy for the implantation of this technique, which is convenient not only for cardiologist and surgeon but also in economic terms, should be decided on with collaboration of cardiology and cardiovascular surgery teams. In this article, advantages of the proximal anastomotic markers during the postoperative follow-up and re-angiography have been presented with the related literature review. PMID:12134539

  6. Detail of north intermediate abutment pylon showing proximity of adjacent ...

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

    Detail of north intermediate abutment pylon showing proximity of adjacent 1001-1007 East First Street (James K. Hill and Sons Pickle Works Building), facing east - First Street Bridge, Spanning Los Angeles River at First Street, Los Angeles, Los Angeles County, CA

  7. Technique for temperature compensation of eddy-current proximity probes

    NASA Technical Reports Server (NTRS)

    Masters, Robert M.

    1989-01-01

    Eddy-current proximity probes are used in turbomachinery evaluation testing and operation to measure distances, primarily vibration, deflection, or displacment of shafts, bearings and seals. Measurements of steady-state conditions made with standard eddy-current proximity probes are susceptible to error caused by temperature variations during normal operation of the component under investigation. Errors resulting from temperature effects for the specific probes used in this study were approximately 1.016 x 10 to the -3 mm/deg C over the temperature range of -252 to 100 C. This report examines temperature caused changes on the eddy-current proximity probe measurement system, establishes their origin, and discusses what may be done to minimize their effect on the output signal. In addition, recommendations are made for the installation and operation of the electronic components associated with an eddy-current proximity probe. Several techniques are described that provide active on-line error compensation for over 95 percent of the temperature effects.

  8. Residential proximity to gasoline service stations and preterm birth.

    PubMed

    Huppé, Vicky; Kestens, Yan; Auger, Nathalie; Daniel, Mark; Smargiassi, Audrey

    2013-10-01

    Preterm birth (PTB) is a growing public health problem potentially associated with ambient air pollution. Gasoline service stations can emit atmospheric pollutants, including volatile organic compounds potentially implicated in PTB. The objective of this study was to evaluate the relationship between residential proximity to gasoline service stations and PTB. Singleton live births on the Island of Montreal from 1994 to 2006 were obtained (n=267,478). Gasoline service station locations, presence of heavy-traffic roads, and neighborhood socioeconomic status (SES) were determined using a geographic information system. Multivariable logistic regression was used to analyze the association between PTB and residential proximity to gasoline service stations (50, 100, 150, 200, 250, and 500 m), accounting for maternal covariates, neighborhood SES, and heavy-traffic roads. For all distance categories beyond 50 m, presence of service stations was associated with a greater odds of PTB. Associations were robust to adjustment for maternal covariates for distance categories of 150 and 200 m but were nullified when adjusting for neighborhood SES. In analyses accounting for the number of service stations, the likelihood of PTB within 250 m was statistically significant in unadjusted models. Associations were, however, nullified in models accounting for maternal covariates or neighborhood SES. Our results suggest that there is no clear association between residential proximity to gasoline service stations in Montreal and PTB. Given the correlation between proximity of gasoline service stations and SES, it is difficult to delineate the role of these factors in PTB. PMID:23625119

  9. Proximal femoral diaphyseal cross-sectional geometry in Orrorin tugenensis.

    PubMed

    Bleuze, M

    2012-06-01

    Functional adaptations in femora attributed to Orrorin tugenensis provide a unique opportunity to examine locomotor behavior very early in the hominin lineage. This study examines relative cortical thickness, cortical area (CA) relative to the polar moment of area (J), and J relative to femoral head superoinferior diameter (FHD) in the proximal femur of O. tugenensis (BAR 1002'00 and BAR 1003'00), and compares patterns in this early hominin with those in a sample of modern humans (N=31), Plio-Pleistocene fossil hominins (N=8), Pan troglodytes troglodytes (N=13), and Pan paniscus (N=3). Relative cortical thickness and CA relative to J in the proximal femur of O. tugenensis are comparable to patterns generally found in other fossil hominins. Proximal femoral diaphyseal J relative to FHD in BAR 1002'00 is similar to patterns found in fossil hominins typically attributed to a non-Homo genus (i.e. SK 82, SK 97, and KNM-ER 738). Cross-sectional geometric patterns in the proximal femur of Orrorin are not unlike those generally found in australopithecines and fossil Homo. While the results of this study cannot confirm unequivocally that Orrorin was an obligate biped, a mode of locomotion comparable to that proposed for australopithecines cannot be ruled out. PMID:22609080

  10. Challenger's RMS arm grasps SPAS-01 during proximity operations

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Challenger's remote manipulator system (RMS) arm grasps Shuttle pallet satellite (SPAS-01) during proximity operations. Behind the SPAS-01 can be seen the clouded surface of the earth. The frame shows a number of reflections on the window, located overhead in the aft flight deck.

  11. Correction of Misclassifications Using a Proximity-Based Estimation Method

    NASA Astrophysics Data System (ADS)

    Niemistö, Antti; Shmulevich, Ilya; Lukin, Vladimir V.; Dolia, Alexander N.; Yli-Harja, Olli

    2004-12-01

    An estimation method for correcting misclassifications in signal and image processing is presented. The method is based on the use of context-based (temporal or spatial) information in a sliding-window fashion. The classes can be purely nominal, that is, an ordering of the classes is not required. The method employs nonlinear operations based on class proximities defined by a proximity matrix. Two case studies are presented. In the first, the proposed method is applied to one-dimensional signals for processing data that are obtained by a musical key-finding algorithm. In the second, the estimation method is applied to two-dimensional signals for correction of misclassifications in images. In the first case study, the proximity matrix employed by the estimation method follows directly from music perception studies, whereas in the second case study, the optimal proximity matrix is obtained with genetic algorithms as the learning rule in a training-based optimization framework. Simulation results are presented in both case studies and the degree of improvement in classification accuracy that is obtained by the proposed method is assessed statistically using Kappa analysis.

  12. Proximal Positioning: A Strategy of Practice in Violin Pedagogy.

    ERIC Educational Resources Information Center

    Gholson, Sylvia A.

    1998-01-01

    Attempts to identify and characterize patterns of expert teaching practice as they occur in context, and to confirm these patterns through processes of verification. Observes teacher Dorothy DeLay in her studio, documenting her teaching through notes, audiotapes, and contextual artifacts. Discusses DeLay's theory of proximal positioning in…

  13. Proximity to Coast Is Linked to Climate Change Belief

    PubMed Central

    Milfont, Taciano L.; Evans, Laurel; Sibley, Chris G.; Ries, Jan; Cunningham, Andrew

    2014-01-01

    Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local. PMID:25047568

  14. Principles of ER coranslational translocation revealed by proximity-specific ribosome profiling

    PubMed Central

    Jan, Calvin H.; Williams, Christopher C.; Weissman, Jonathan S.

    2014-01-01

    Localized protein synthesis is a fundamental mechanism for creating distinct subcellular environments. Here we developed a generalizable proximity-specific ribosome profiling strategy that enables global analysis of translation in defined subcellular locations. We applied this approach to the endoplasmic reticulum (ER) in yeast and mammals. We observed the large majority of secretory proteins to be cotranslationally translocated, including substrates capable of post-translational insertion in vitro. Distinct translocon complexes engaged nascent chains at different points during synthesis. Whereas most proteins engaged the ER immediately after or even before signal sequence (SS) emergence, a class of Sec66-dependent proteins entered with a looped SS conformation. Finally, we observed rapid ribosome exchange into the cytosol after translation termination. These data provide insights into how distinct translocation mechanisms act in concert to promote efficient cotranslational recruitment. PMID:25378630

  15. Cast index in predicting outcome of proximal pediatric forearm fractures

    PubMed Central

    Sheikh, Hassaan Qaiser; Malhotra, Karan; Wright, Phil

    2015-01-01

    Background: Many pediatric forearm fractures can be treated in plaster following closed reduction. The cast index (CI, a ratio of anteroposterior to lateral internal diameters of the cast at the fracture site) is a simple, reliable marker of quality of molding and a CI of >0.8 correlates with increased risk of redisplacement. Previously, CI has been applied to all forearm fractures. We hypothesize that an acceptable CI is more difficult to achieve and does not predict outcome in fractures of the proximal forearm. Materials and Methods: Seventynine cases of pediatric forearm fractures initially treated by manipulation alone over a year were included in this retrospective radiographic analysis. The CI was calculated from the post manipulation radiographs. All fractures were divided as either proximal or distal half forearm based on the location of the radius fracture. Subsequent radiographs were reviewed to assess redisplacement and reoperation. Results: The mean CI was 0.77. Remanipulation was required in five cases (6%), all distal half fractures – mean CI 0.79. CI was higher in proximal half forearm fractures (0.83 vs. 0.76, P = 0.006), nonetheless these fractures did not re-displace more than distal fractures. Conclusion: Cast index is useful in predicting redisplacement of manipulated distal forearm fractures. We found that in proximal half forearm fractures it is difficult to achieve a CI of <0.8, but increased CI does not predict loss of position in these fractures. We therefore discourage the use of CI in proximal half forearm fractures. PMID:26229159

  16. SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule

    PubMed Central

    Platt, Kenneth A.; Cunard, Robyn; Schroth, Jana; Whaley, Jean; Thomson, Scott C.; Koepsell, Hermann; Rieg, Timo

    2011-01-01

    Mutations in the gene encoding for the Na+-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood. Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterized SGLT2-deficient mice. In wild-type (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal tubule. Sglt2−/− mice had glucosuria, polyuria, and increased food and fluid intake without differences in plasma glucose concentrations, GFR, or urinary excretion of other proximal tubular substrates (including amino acids) compared with WT mice. SGLT2 deficiency did not associate with volume depletion, suggested by similar body weight, BP, and hematocrit; however, plasma renin concentrations were modestly higher and plasma aldosterone levels were lower in Sglt2−/− mice. Whole-kidney clearance studies showed that fractional glucose reabsorption was significantly lower in Sglt2−/− mice compared with WT mice and varied in Sglt2−/− mice between 10 and 60%, inversely with the amount of filtered glucose. Free-flow micropuncture revealed that for early proximal collections, 78 ± 6% of the filtered glucose was reabsorbed in WT mice compared with no reabsorption in Sglt2−/− mice. For late proximal collections, fractional glucose reabsorption was 93 ± 1% in WT and 21 ± 6% in Sglt2−/− mice, respectively. These results demonstrate that SGLT2 mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. This mouse model mimics and explains the glucosuric phenotype of individuals carrying SLC5A2 mutations. PMID:20616166

  17. The He II Proximity Effect and The Lifetime of Quasars

    NASA Astrophysics Data System (ADS)

    Khrykin, I. S.; Hennawi, J. F.; McQuinn, M.; Worseck, G.

    2016-06-01

    The lifetime of quasars is fundamental for understanding the growth of supermassive black holes, and is an important ingredient in models of the reionization of the intergalactic medium (IGM). However, despite various attempts to determine quasar lifetimes, current estimates from a variety of methods are uncertain by orders of magnitude. This work combines cosmological hydrodynamical simulations and 1D radiative transfer to investigate the structure and evolution of the He ii Lyα proximity zones around quasars at z ≃ 3–4. We show that the time evolution in the proximity zone can be described by a simple analytical model for the approach of the He ii fraction {x}{He{{II}}}(t) to ionization equilibrium, and use this picture to illustrate how the transmission profile depends on the quasar lifetime, quasar UV luminosity, and the ionization state of Helium in the ambient IGM (i.e., the average He ii fraction, or equivalently the metagalactic He ii ionizing background). A significant degeneracy exists between the lifetime and the average He ii fraction, however the latter can be determined from measurements of the He ii Lyα optical depth far from quasars, allowing the lifetime to be measured. We advocate stacking existing He ii quasar spectra at z ∼ 3, and show that the shape of this average proximity zone profile is sensitive to lifetimes as long as ∼30 Myr. At higher redshift z ∼ 4 where the He ii fraction is poorly constrained, degeneracies will make it challenging to determine these parameters independently. Our analytical model for He ii proximity zones should also provide a useful description of the properties of H i proximity zones around quasars at z ≃ 6–7.

  18. In vitro footprinting of promoter regions within supercoiled plasmid DNA

    PubMed Central

    Sun, Daekyu

    2010-01-01

    Polypurine/polypyrimidine (pPU/pPY) tracts, which exist in the promoter regions of many growth-related genes, have been proposed to be very dynamic in their conformation. In this chapter, we describe a detailed protocol for DNase I and S1 nuclease footprinting experiments with supercoiled plasmid DNA containing such the promoter regions to probe whether there are conformational transitions to B-type DNA, melted DNA and G-quadruplex structures within this tract. This is demonstrated with the proximal promoter region of the human vascular endothelial growth factor (VEGF) gene, which also contains multiple binding sites for Sp1 and Egr-1 transcription factors. PMID:19997887

  19. Proximate and landscape factors influence grassland bird distributions

    USGS Publications Warehouse

    Cunningham, M.A.; Johnson, D.H.

    2006-01-01

    Ecologists increasingly recognize that birds can respond to features well beyond their normal areas of activity, but little is known about the relative importance of landscapes and proximate factors or about the scales of landscapes that influence bird distributions. We examined the influences of tree cover at both proximate and landscape scales on grassland birds, a group of birds of high conservation concern, in the Sheyenne National Grassland in North Dakota, USA. The Grassland contains a diverse array of grassland and woodland habitats. We surveyed breeding birds on 2015 100 m long transect segments during 2002 and 2003. We modeled the occurrence of 19 species in relation to habitat features (percentages of grassland, woodland, shrubland, and wetland) within each 100-m segment and to tree cover within 200-1600 m of the segment. We used information-theoretic statistical methods to compare models and variables. At the proximate scales, tree cover was the most important variable, having negative influences on 13 species and positive influences on two species. In a comparison of multiple scales, models with only proximate variables were adequate for some species, but models combining proximate with landscape information were best for 17 of 19 species. Landscape-only models were rarely competitive. Combined models at the largest scales (800-1600 m) were best for 12 of 19 species. Seven species had best models including 1600-m landscapes plus proximate factors in at least one year. These were Wilson's Phalarope (Phalaropus tricolor), Sedge Wren (Cistothorus platensis), Field Sparrow (Spizella pusilla), Grasshopper Sparrow (Ammodramus savannarum), Bobolink (Dolychonix oryzivorus), Red-winged Blackbird (Agelaius phoeniceus), and Brown-headed Cowbird (Molothrus ater). These seven are small-bodied species; thus larger-bodied species do not necessarily respond most to the largest landscapes. Our findings suggest that birds respond to habitat features at a variety of

  20. Interlaminated ice-proximal glacimarine sediments in Muir Inlet, Alaska

    USGS Publications Warehouse

    Mackiewicz, N.E.; Powell, R.D.; Carlson, P.R.; Molnia, B.F.

    1984-01-01

    Muir Inlet in Glacier Bay, Alaska, is a glacial fjord receiving a tremendous volume of sediment annually. The rate of sediment accumulation is greatest proximal to Muir Glacier (about 9 m yr-1) and decreases away from the glacier. The primary sediment sources are meltwater streams discharging at subglacial and ice-marginal positions to form overflows, interflows, and underflows (continuous turbidity currents). Overflows and interflows interact with diurnal tidal currents and their volume and sediment concentration varies diurnally and annually with meltwater discharge. These effects produce cyclic deposits of a thin fine-grained sand or silt lamina that grades normally to a thicker poorly to very poorly sorted mud lamina. This lamina couplet is termed a cyclopel. Underflows are suggested to occur in this glacimarine environment because of conditions unique to subglacial fluvial systems. Underflow deposits occur only in proximal positions (177 ??m) is ubiquitous, though low (<5% by weight), and occurs as isolated particles, frozen pellets, or as lenses that in cores may have a lamina appearance. Proximally, ice-rafted debris is difficult to identify because proximal sediment is often as coarse-grained. Deposited sediment may be reworked by tidal currents, and sediment gravity flows. Depositional processes operating in Muir Inlet produce interlaminated sand/silt/clay that characterizes sediment proximal to a glacier and fines seaward to mud. Sediment is classified into one of three sediment types: 1. (1) Type I sediment is very fine grained (mean 8.65-7.17 ??), low in sand (0.1-11.2%), and very poorly to poorly sorted. It is the dominant sediment type in Muir Inlet, and is transported by plumes and deposited by suspension settling. 2. (2) Type II sediment is fine- to coarse-grained (mean 6.70-3.12 ??), low to high in sand (5.1-86.6%), and very poorly to moderately sorted. It represents reworked sediment, proximal plume deposits, or coarse-grained laminae of cyclopels

  1. Proximate and landscape factors influence grassland bird distributions.

    PubMed

    Cunningham, Mary Ann; Johnson, Douglas H

    2006-06-01

    Ecologists increasingly recognize that birds can respond to features well beyond their normal areas of activity, but little is known about the relative importance of landscapes and proximate factors or about the scales of landscapes that influence bird distributions. We examined the influences of tree cover at both proximate and landscape scales on grassland birds, a group of birds of high conservation concern, in the Sheyenne National Grassland in North Dakota, USA. The Grassland contains a diverse array of grassland and woodland habitats. We surveyed breeding birds on 2015 100 m long transect segments during 2002 and 2003. We modeled the occurrence of 19 species in relation to habitat features (percentages of grassland, woodland, shrubland, and wetland) within each 100-m segment and to tree cover within 200-1600 m of the segment. We used information-theoretic statistical methods to compare models and variables. At the proximate scales, tree cover was the most important variable, having negative influences on 13 species and positive influences on two species. In a comparison of multiple scales, models with only proximate variables were adequate for some species, but models combining proximate with landscape information were best for 17 of 19 species. Landscape-only models were rarely competitive. Combined models at the largest scales (800-1600 m) were best for 12 of 19 species. Seven species had best models including 1600-m landscapes plus proximate factors in at least one year. These were Wilson's Phalarope (Phalaropus tricolor), Sedge Wren (Cistothorus platensis), Field Sparrow (Spizella pusilla), Grasshopper Sparrow (Ammodramus savannarum), Bobolink (Dolychonix oryzivorus), Red-winged Blackbird (Agelaius phoeniceus), and Brown-headed Cowbird (Molothrus ater). These seven are small-bodied species; thus larger-bodied species do not necessarily respond most to the largest landscapes. Our findings suggest that birds respond to habitat features at a variety of

  2. Characterization and regulation of the rat and human ghrelin promoters.

    PubMed

    Wei, Wei; Wang, Guiyun; Qi, Xiang; Englander, Ella W; Greeley, George H

    2005-03-01

    Ghrelin is a recently discovered stomach hormone and endogenous ligand for the GH secretagogue receptor. The aim of these studies is to elucidate molecular mechanisms underlying regulation of the ghrelin gene. Distal and proximal transcription initiation sites are present. A short transcript, a product of the proximal site, showed a more widespread distribution. Two sets of 5'-upstream segments of the rat and human ghrelin genes were cloned and sequenced. Rat promoter segments upstream of the distal site showed highest activity in kidney (COS-7) and stomach (AGS) cells, whereas human promoter segments upstream of the proximal site showed highest activity in AGS and pituitary (GH3) cells in transient transfection assays. For the human, the core promoter spanned -667 to -468 bp, including the noncoding exon 1 and a short 5' sequence of intron 1. For the rat, the core promoter spanned -581 to -469 bp, and inclusion of exon 1 and a short 5'-sequence of intron 1 reduced activity by 67%. Mutation of initiator-like elements in the rat lowered activity by 20-50%, whereas in the human, all activity was abolished. Overexpression of upstream stimulatory factors increased ghrelin core promoter activity. Fasting increases stomach ghrelin expression, glucagon-a fasting-induced hormone, increased ghrelin expression in vivo in rats, and promoter activity by approximately 25-50%. Together, these findings indicate that structural differences between the rat and human ghrelin core promoters may account in part for the differences in their transcriptional regulation. Nonetheless, upstream stimulatory factor and glucagon exert similar effects on regulation of rat and human ghrelin promoters. PMID:15604212

  3. Disproportionate Proximity to Environmental Health Hazards: Methods, Models, and Measurement

    PubMed Central

    Maantay, Juliana A.; Brender, Jean D.

    2011-01-01

    We sought to provide a historical overview of methods, models, and data used in the environmental justice (EJ) research literature to measure proximity to environmental hazards and potential exposure to their adverse health effects. We explored how the assessment of disproportionate proximity and exposure has evolved from comparing the prevalence of minority or low-income residents in geographic entities hosting pollution sources and discrete buffer zones to more refined techniques that use continuous distances, pollutant fate-and-transport models, and estimates of health risk from toxic exposure. We also reviewed analytical techniques used to determine the characteristics of people residing in areas potentially exposed to environmental hazards and emerging geostatistical techniques that are more appropriate for EJ analysis than conventional statistical methods. We concluded by providing several recommendations regarding future research and data needs for EJ assessment that would lead to more reliable results and policy solutions. PMID:21836113

  4. Ulnar neuropathy with prominent proximal Martin-Gruber anastomosis.

    PubMed

    Burakgazi, Ahmet Z; Russo, Mary; Bayat, Elham; Richardson, Perry K

    2014-07-01

    Martin-Gruber anastomosis (MGA) is the most common nerve anastomosis in the upper extremities and it crosses from the median nerve to the ulnar nerve. Proximal MGA is an under recognized anastomosis between the ulnar and median nerves at or above the elbow and should not be missed during nerve conduction studies. We presented two patients with ulnar neuropathy mimicking findings including numbness and tingling of the 4th and 5th digits and mild weakness of intrinsic hand muscles. However, both cases had an apparently remarkable conduction block between the below- and above-elbow sites that was disproportionate to their clinical findings. To explain this discrepancy, a large MGA was detected with stimulation of the median nerve at the elbow. Thus, proximal MGA should be considered in ulnar neuropathy at the elbow when apparent conduction block or/and discrepancy between clinical and electrodiagnostic findings is found. PMID:24147570

  5. Scintillation Proximity Radioimmunoassay Utilizing 125I-Labeled Ligands

    NASA Astrophysics Data System (ADS)

    Udenfriend, Sidney; Diekmann Gerber, Louise; Brink, Larry; Spector, Sydney

    1985-12-01

    A unique type of radioimmunoassay is described that does not require centrifugation or separation. Microbeads containing a fluorophor are covalently linked to antibody. When an 125I-labeled antigen is added it binds to the beads and, by its proximity, the emitted short-range electrons of the 125I excite the fluorophor in the beads. The light emitted can be measured in a standard scintillation counter. Addition of unlabeled antigen from tissue extracts displaces the labeled ligand and diminishes the fluorescent signal. Application of scintillation proximity immunoassay to tissue enkephalins, serum thyroxin, and urinary morphine is described. Applications of the principle to study the kinetics of interaction between receptors and ligands are discussed.

  6. Space station proximity operations windows: Human factors design guidelines

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1987-01-01

    Proximity operations refers to all activities outside the Space Station which take place within a 1-km radius. Since there will be a large number of different operations involving manned and unmanned vehicles, single- and multiperson crews, automated and manually controlled flight, a wide variety of cargo, and construction/repair activities, accurate and continuous human monitoring of these operations from a specially designed control station on Space Station will be required. Total situational awareness will be required. This paper presents numerous human factors design guidelines and related background information for control windows which will support proximity operations. Separate sections deal with natural and artificial illumination geometry; all basic rendezvous vector approaches; window field-of-view requirements; window size; shape and placement criteria; window optical characteristics as they relate to human perception; maintenance and protection issues; and a comprehensive review of windows installed on U.S. and U.S.S.R. manned vehicles.

  7. Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

    NASA Technical Reports Server (NTRS)

    Sadleir, John E.; Smith, Stephen J.; Bandler, SImon R.; Chervenak, James A.; Clem, John R.

    2009-01-01

    We have found experimentally that the critical current of a square superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. The observed behavior has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. We have observed the proximity effect in these devices over extraordinarily long lengths exceeding 100 microns.

  8. Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

    NASA Technical Reports Server (NTRS)

    Sadlier, John E.; Smith, Stephen J.; Bandler, Simon R.; Chervenak, James A.; Clem, John R.

    2009-01-01

    We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 micrometers, 1450 times the mean-free path.

  9. Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

    NASA Technical Reports Server (NTRS)

    Sadleir, John E.; Smith, Stephen J.; Bandler, Simon R.; Chervenak, James A.; Clem, John R.

    2010-01-01

    We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 micrometers, 1450 times the mean-free path.

  10. Proximal gastric vagotomy: a district general hospital experience.

    PubMed Central

    Wood, J. J.; Ryan, J. M.; Anders, C. J.

    1983-01-01

    A district general hospital experience with proximal gastric vagotomy over a nine-year period is reported. One hundred and eight patients undergoing the operation for chronic duodenal ulcer were assessed. The follow-up period was 1-9 years (mean 4 years and 7 months). The results were graded using a modification of the classification of Visick (1948). Over 85% of our patients were satisfied with their results. (Visick 1 and 2). Recurrent ulceration was noted in 3.9% of our series (4 cases). There were no deaths and few complications. The technique used by us is described briefly and the role of proximal gastric vagotomy in a district general hospital is discussed. PMID:6859783

  11. Automated space vehicle control for rendezvous proximity operations

    NASA Technical Reports Server (NTRS)

    Lea, Robert N.

    1988-01-01

    Rendezvous during the unmanned space exploration missions, such as a Mars Rover/Sample Return will require a completely automatic system from liftoff to docking. A conceptual design of an automated rendezvous, proximity operations, and docking system is being implemented and validated at the Johnson Space Center (JSC). The emphasis is on the progress of the development and testing of a prototype system for control of the rendezvous vehicle during proximity operations that is currently being developed at JSC. Fuzzy sets are used to model the human capability of common sense reasoning in decision making tasks and such models are integrated with the expert systems and engineering control system technology to create a system that performs comparably to a manned system.

  12. Automated space vehicle control for rendezvous proximity operations

    NASA Technical Reports Server (NTRS)

    Lea, Robert N.

    1988-01-01

    Rendezvous during the unmanned space exploration missions, such as a Mars Rover/Sample Return will require a completely automatic system from liftoff to docking. A conceptual design of an automated rendezvous, proximity operations, and docking system is being implemented and validated at the Johnson Space Center (JSC). The emphasis is on the progress of the development and testing of a prototype system for control of the rendezvous vehicle during proximity operations that is currently being developed at JSC. Fuzzy sets are used to model the human capability of common sense reasoning in decision-making tasks and such models are integrated with the expert systems and engineering control system technology to create a system that performs comparably to a manned system.

  13. Proximity nanovalve with large phase-tunable thermal conductance

    SciTech Connect

    Strambini, E. Giazotto, F.; Bergeret, F. S.

    2014-08-25

    We propose a phase-controlled heat-flux quantum valve based on the proximity effect driven by a superconducting quantum interference proximity transistor (SQUIPT). Its operation relies on the phase-dependent quasiparticle density of states in the Josephson weak-link of the SQUIPT which controls thermal transport across the device. In a realistic Al/Cu-based setup the structure can provide efficient control of thermal current inducing temperature swings exceeding ∼100 mK, and flux-to-temperature transfer coefficients up to ∼500 mK/Φ{sub 0} below 100 mK. The nanovalve performances improve by lowering the bath temperature, making the proposed structure a promising building-block for the implementation of coherent caloritronic devices operating below 1 K.

  14. Rendezvous and Proximity Operations of the Space Shuttle

    NASA Technical Reports Server (NTRS)

    Goodman, John L.

    2005-01-01

    Space Shuttle rendezous missions presented unique challenges that were not fully recognized when the Shuttle was designed. Rendezvous targets could be passive (i.e., no lights or transponders), and not designed to facilitate Shuttle rendezvous, proximity operations and retrieval. Shuttle reaction control system jet plume impingement on target spacecraft presented induced dynamics, structural loading and contamination concerns. These issues, along with limited forward reaction control system propellant, drove a change from the Gemimi/Apollo coelliptic profile heritage to a stable orbit profile, and the development of new proximity operations techniques. Multiple scientific and on-orbit servicing missions and crew exchange, assembly and replinishment flights to Mir and to the International Space Station drove further profile and piloting technique changes, including new relative navigation sensors and new computer generated piloting cues.

  15. PROXIMAL FEMORAL EPIPHYSIOLYSIS AND SUBCLINICAL HYPOTHYROIDISM: CASE REPORT

    PubMed Central

    de Mello, Grasiele Correa; Grossi, Gabriela; Coelho, Sílvio Pereira

    2015-01-01

    Proximal femoral epiphysiolysis is an orthopedic disease that is prevalent during adolescence, because this coincides with the time of greatest growth of osteomuscular structures. Curiously, some patients present this disease early, and this outcome converts to the possible etiological explanation that the slippage might occur through a growth spurt. For these patients, the genesis of the slippage has not yet been elucidated, but endocrine disorders have been noted as possible causes. In an attempt to strengthen the theory of endocrinological etiology and present the results from surgical treatment for this pathological condition, the case of a male patient aged 9 years and 3 months with proximal femoral epiphysiolysis and subclinical hypothyroidism who was diagnosed and treated at our university's teaching hospital is reported here. PMID:27047883

  16. Scintillation proximity radioimmunoassay utilizing 125I-labeled ligands

    SciTech Connect

    Udenfriend, S.; Gerber, L.D.; Brink, L.; Spector, S.

    1985-12-01

    A unique type of radioimmunoassay is described that does not require centrifugation or separation. Microbeads containing a fluorophor are covalently linked to antibody. When an /sup 125/I-labeled antigen is added it binds to the beads and, by its proximity, the emitted short-range electrons of the /sup 125/I excite the fluorophor in the beads. The light emitted can be measured in a standard scintillation counter. Addition of unlabeled antigen from tissue extracts displaces the labeled ligand and diminishes the fluorescent signal. Application of scintillation proximity immunoassay to tissue enkephalins, serum thyroxin, and urinary morphine is described. Applications of the principle to study the kinetics of interaction between receptors and ligands are discussed.

  17. Human exploration of near Earth Asteroids: Architecture of proximity operations

    NASA Astrophysics Data System (ADS)

    Tardivel, Simon; Takahashi, Yu; Zimmer, Aline K.; Herman, Jonathan F. C.; Reijneveld, Johannes P. J.; Dunlop, Kathryn L.; Scheeres, Daniel J.

    2015-05-01

    This paper outlines the strategic approach to realize a human mission to an asteroid, focusing specifically on the proximity operations. The risks and challenges posed by asteroid surfaces to in-situ investigations force the proximity operations to be done by the intermediary of robotic explorers. In this architecture, a precursor is sent years in advance to a potential target asteroids. Its main goals are the characterization of the gravity field and of the surface behavior. If the target is found suitable, the manned mission then proceeds. With their main spacecraft stationed on a stable orbit around the asteroid, the astronauts are transported to the surface via a small, unpressurized spacecraft. Hovering a few meters above the surface, they deploy and command small robotic landers that perform scientific operations at the surface.

  18. A critical assessment of proximal macrotexturing on cemented femoral components.

    PubMed

    Duffy, G P; Muratoglu, O K; Biggs, S A; Larson, S L; Lozynsky, A J; Harris, W H

    2001-12-01

    We analyzed the cement-metal interface of 3 different types of femoral components that had proximal macrotexturing after in vitro insertion and after fatigue testing designed to produce debonding and micromotion. These components were compared with clinical retrieval specimens. The cement did not flow into the macrotexturing; rather, hollow, brittle volcanoes or calderas were formed. These fragile protrusions of cement become worn down or abraded by debonded components. This abrasion of cement may contribute to the early and aggressive osteolysis seen in some of these early failures with proximal macrotextured components. The formation of these volcanos and calderas can be aborted by placing bone-cement onto the macrotexturing before stem insertion. This simple technique allows the macrotexturing to be filled with cement. PMID:11742450

  19. STRaND-2: Visual inspection, proximity operations & nanosatellite docking

    NASA Astrophysics Data System (ADS)

    Bridges, C. P.; Taylor, B.; Horri, N.; Underwood, C. I.; Kenyon, S.; Barrera-Ars, J.; Pryce, L.; Bird, R.

    The Surrey Training Research and Nanosatellite Demonstrator (STRaND) programme has been success in identifying and creating a leading low-cost nanosatellite programme with advanced attitude and orbit control system (AOCS) and experimental computing platforms based on smart-phone technologies. The next demonstration capabilities, that provide a challenging mission to the existing STRaND platform, is to perform visual inspection, proximity operations and nanosatellite docking. Visual inspection is to be performed using a COTS LIDAR system to estimate range and pose under 100 m. Proximity operations are controlled using a comprehensive guidance, navigation and control (GNC) loop in a polar form of the Hills Clohessy Wiltshire (HCW) frame including J2 perturbations. And finally, nanosatellite docking is performed at under 30 cm using a series of tuned magnetic coils. This paper will document the initial experiments and calculations used to qualify LIDAR components, size the mission thrust and tank requirements, and air cushion table demonstrations of the docking mechanism.

  20. Proximity potential for heavy ion reactions on deformed nuclei

    SciTech Connect

    Baltz, A. J.; Bayman, B. F.

    1982-01-01

    The usual treatment of the deformed optical model for analysis of heavy ion induced inelastic scattering data involves a deformed (target) radius, a spherical (projectile) radius and a potential strength dependent on the surface separation along the line between the two centers. Several authors using various approaches have shown that this center line potential is geometrically inadequate especially for description of higher L deformation parameters probed in heavy ion induced inelastic scattering experiments. A quantitatively adequate form of the deformed proximity potential suitable for use with a coupled channels reaction code in the analysis of inelastic scattering data above the Coulomb barrier is described. A major objective is to be able to extract reliably higher deformed multipole moments from such data. The deformed potential calculated in the folding model will serve as a geometrically exact benchmark to evaluate the accuracy of the proximity potential prescriptions. (WHK)

  1. Human proximal femur bone adaptation to variations in hip geometry.

    PubMed

    Machado, M M; Fernandes, P R; Zymbal, V; Baptista, F

    2014-10-01

    The study of bone mass distribution at proximal femur may contribute to understand the role of hip geometry on hip fracture risk. We examined how bone mineral density (BMD) of proximal femur adapts to inter individual variations in the femoral neck length (FNL), femoral neck width (FNW) and neck shaft angle (NSA). A parameterized and dimensionally scalable 3-D finite element model of a reference proximal femur geometry was incrementally adjusted to adopt physiological ranges at FNL (3.90-6.90cm), FNW (2.90-3.46cm), and NSA (109-141º), yielding a set of femora with different geometries. The bone mass distribution for each femur was obtained with a suitable bone remodelling model. The BMDs at the integral femoral neck (FN) and at the intertrochanteric (ITR) region, as well as the BMD ratio of inferomedial to superolateral (IM:SL) regions of FN and BMD ratio of FN:ITR were used to represent bone mass distribution. Results revealed that longer FNLs present greater BMD (g/cm(3)) at the FN, mainly at the SL region, and at the ITR region. Wider FNs were associated with reduced BMD at the FN, particularly at the SL region, and at the ITR region. Larger NSAs up to 129° were associated with BMD diminutions at the FN and ITR regions and with increases of the IM:SL BMD ratio while NSAs larger than 129° resulted in decrease of the IM:SL BMD ratio. These findings suggest hip geometry as moderator of the mechanical loading influence on bone mass distribution at proximal femur with higher FNL favoring the BMD of FN and ITR regions and greater FNW and NSA having the opposite effect. Augmented values of FNL and FNW seem also to favor more the BMD at the superolateral than at the inferomedial FN region. PMID:25016094

  2. High-Energy Proximal Femur Fractures in Geriatric Patients

    PubMed Central

    Hahnhaussen, Jens; Hak, David J; Weckbach, Sebastian; Ertel, Wolfgang; Stahel, Philip F

    2011-01-01

    Background: There is limited information in the literature on the outcomes and complications in elderly patients who sustain high-energy hip fractures. As the population ages, the incidence of high-energy geriatric hip fractures is expected to increase. The purpose of this study was to analyze the outcomes and complications in patients aged 65 years or older, who sustained a high-energy proximal femur fracture. Methods: Retrospective review of a prospective trauma database from January 2000 to April 2011 at a single US academic level-1 trauma center. Inclusion criteria consisted of all patients of age 65 years or older, who sustained a proximal femur fracture related to a high-energy trauma mechanism. Details concerning injury, acute treatment, and clinical course and outcome were obtained from medical records and radiographs. Results: We identified 509 proximal femur fractures in patients older than 65 years of age, of which 32 (6.3%) were related to a high-energy trauma mechanism. The mean age in the study group was 72.2 years (range 65-87), with a mean injury severity score of 20 points (range 9-57). Three patients died before discharge (9.4%), and 22 of 32 patients sustained at least one complication (68.8%). Blunt chest trauma represented the most frequently associated injury, and the main root cause of pulmonary complications. The patients' age and comorbidities did not significantly correlate with the rate of complications and the 1-year mortality. Conclusions: High-energy proximal femur fractures in elderly patients are not very common and are associated with a low in-hospital mortality rate of less than 10%, despite high rate of complications of nearly 70%. This selective cohort of patients requires a particular attention to respiratory management due to the high incidence of associated chest trauma. PMID:23569690

  3. Lung cancer, proximity to industry, and poverty in northeast England.

    PubMed Central

    Pless-Mulloli, T; Phillimore, P; Moffatt, S; Bhopal, R; Foy, C; Dunn, C; Tate, J

    1998-01-01

    This study assesses whether deprived populations living close to industry experience greater mortality from lung cancer than populations with comparable socioeconomic characteristics living farther away. Mortality data, census data, a postal survey of living circumstances, historic and contemporary data on air quality and a historic land-use survey were used. Analysis was based on two conurbations in England, Teesside and Sunderland. Housing estates in Teesside were selected based on socioeconomic criteria and distinguished by proximity to steel and chemical industries; they were grouped into three zones: near (A), intermediate (B), and farther (C), with a single zone in Sunderland. We included 14,962 deaths in 27 estates. Standardized mortality ratios (SMR) for lung cancer [International Classification of Diseases #9 (ICD-9) 162] and cancers other than lung (ICD-9 140-239, excluding 162), and sex ratios were calculated. Mortality from lung cancer was well above national levels in all zones. For men, a weak gradient corresponding with proximity to industry at younger ages reversed at older ages. In women 0-64 years of age, stronger gradients in lung cancer mortality corresponded with proximity to industry across zones A, B, and C (SMR = 393, 251, 242, respectively). Overall rates in Teesside were higher than Sunderland rates for women aged 0-64 years (SMR = 287 vs. 185) and 65-74 years (SMR = 190 vs. 157). The association between raised lung cancer mortality and proximity to industry in women under 75 years of age could not be explained by smoking, occupation, socioeconomic factors, or artifact. Explanations for differences between men and women may include gender-specific occupational experiences and smoking patterns. Our judgment is that the observed gradient in women points to a role for industrial air pollution. Images Figure 1 Figure 2 PMID:9485483

  4. Mesoscale Nanoparticles Selectively Target the Renal Proximal Tubule Epithelium

    PubMed Central

    Williams, Ryan M.; Shah, Janki; Ng, Brandon D.; Minton, Denise R.; Gudas, Lorraine J.; Park, Christopher Y.; Heller, Daniel A.

    2015-01-01

    We synthesized “mesoscale” nanoparticles, approximately 400 nm in diameter, which unexpectedly localized selectively in renal proximal tubules and up to 7 times more efficiently in the kidney than other organs. Although nanoparticles typically localize in the liver and spleen, modulating their size and opsonization potential allowed for stable targeting of the kidneys through a new proposed uptake mechanism. Applying this kidney targeting strategy, we anticipate use in the treatment of renal disease and the study of renal physiology. PMID:25811353

  5. Evaluation of proximity devices, volume 2, phase 3

    NASA Astrophysics Data System (ADS)

    Nixon, J. H.; Hipp, J. E.; Green, T. C.; Murch, G. H.; Cater, J. P.

    1982-12-01

    Phase 1 of this three phase program consisted of test evaluations of commercially available proximity warning devices. Phase 2 resulted in the design and development of a microprocessor based distributed sensor ac electrometer that measures the electrostatic field at locations along a crane boom. In volume 1 of phase 2 the electrostatic fields around a crane boom were measured by the instrument at high voltage powerlines of various voltages and geometries. Volume 2 of phase 2 contains the appendixes.

  6. Proximal Interruption of the Pulmonary Artery: A Case Series

    PubMed Central

    Anand, S.H.; Mani, Sunithi Elizabeth; Joseph, Elizabeth; Mathai, John

    2015-01-01

    We present a few cases of Proximal Interruption of the Pulmonary Artery, an uncommon developmental anomaly associated with congenital heart disease. The cases had varied clinical presentations. Chest radiograph showed a hypoplastic lung with an ipsilateral small hilum on the side of the interruption and hyperinflation of the contralateral lung. Contrast CT confirmed the diagnosis, demonstrating non-visualization of the left or right pulmonary artery, and other related findings. PMID:26816968

  7. MTF of Proximity-Focused Image Tube in Polychromatic Light.

    PubMed

    Nijhawan, O P; Datta, P K; Sharma, C R

    1975-02-01

    The effect of different conditions of illumination and the spectral sensitivity of the detector on the performance of proximity-focused image tube has been evaluated in terms of the polychromatic modulation transfer function. The physical efficiencies of sources commonly used in the infrared image conversion system have been compared for a Corning glass 2540 glass filter and a GaAs filter having antireflection coatings on both sides. PMID:20134914

  8. Stress fracture of the proximal fibula after total knee arthroplasty.

    PubMed

    Vaish, Abhishek; Vaishya, Raju; Agarwal, Amit Kumar; Vijay, Vipul

    2016-01-01

    We report a rare case of proximal fibular fatigue fracture developing 14 years after total knee arthroplasty in a known case of rheumatoid arthritis. A valgus deformity of the knee can put abnormal stress on the upper fibula leading to its failure. We believe that, as the fibula acts as an important lateral strut, its disruption due to a fracture led to rapid progress of the valgus deformity of the knee in this patient. PMID:27107057

  9. Transverse Stress Fracture of the Proximal Patella: A Case Report.

    PubMed

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-02-01

    Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete.A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity.Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID:26871789

  10. Proximal Interruption of the Pulmonary Artery: A Case Series.

    PubMed

    Anand, S H; Jasper, Anitha; Mani, Sunithi Elizabeth; Joseph, Elizabeth; Mathai, John

    2015-12-01

    We present a few cases of Proximal Interruption of the Pulmonary Artery, an uncommon developmental anomaly associated with congenital heart disease. The cases had varied clinical presentations. Chest radiograph showed a hypoplastic lung with an ipsilateral small hilum on the side of the interruption and hyperinflation of the contralateral lung. Contrast CT confirmed the diagnosis, demonstrating non-visualization of the left or right pulmonary artery, and other related findings. PMID:26816968

  11. Proximal ventricular shunt malfunctions in children: Factors associated with failure.

    PubMed

    Buster, Bryan E; Bonney, Phillip A; Cheema, Ahmed A; Glenn, Chad A; Conner, Andrew K; Safavi-Abbasi, Sam; Andrews, Mason B; Gross, Naina L; Mapstone, Timothy B

    2016-02-01

    Ventricular shunt failures and subsequent revisions are a significant source of patient morbidity. We conducted a review of pediatric patients undergoing placement or revision of ventricular shunts at our institution between January 2007 and December 2008. Patients were followed through to July 2014. Data collected included patient demographics, shunt history and indication for procedure, approach taken for shunt placement, and location of shunt tip in relation to the foramen of Monro. Univariate and multivariate analyses were conducted to identify factors associated with proximal failure. A total of 87 procedures were identified in 40 patients, consisting of 23 initial placements and 64 revisions. Thirty-nine proximal catheter malfunctions were identified. Indications for shunt placement included Chiari II malformation (33%) and intraventricular hemorrhage (33%). Mean follow-up period was 5.5 years. Median time to shunt failure was 1.57 years. In the multivariate model, younger age at placement was associated with decreased time to proximal failure (hazard ratio [HR]=0.80 per increasing year of age, 95% confidence interval [CI] 0.64-0.98). Both anterior approach (HR=0.39, 95% CI 0.23-0.67) and farther distance to foramen of Monro (HR=0.02 per increasing 10mm, 95% CI 0.00-0.22) were associated with increased time to proximal failure when the catheter tip was located within the contralateral lateral ventricle. Optimizing outcomes in patients with shunt-dependent hydrocephalus continues to be a challenge. Despite unsatisfactory outcomes, particularly in the pediatric population, few conclusions can be drawn from studies assessing operative variables. PMID:26601815

  12. Hierarchical e-beam proximity correction in mask making

    NASA Astrophysics Data System (ADS)

    Hofmann, Ulrich; Kalus, Christian K.; Rosenbusch, Anja; Jonckheere, Rik M.; Hourd, Andrew C.

    1996-05-01

    Both e-beam and optical proximity effects are still a major barrier in the transfer of an ULSI design from the CAD station to the printed result on wafer. Optical proximity effect correction (OPC) is shown to be a strong tool to improve the printing latitudes for i-line lithography of 0.35 micrometers feature sizes and below, but leads to fractal geometries around 0.1 micrometers (corresponding to 0.5 micrometers on a 5x reticle). This quantum leap in required minimum linewidth on the mask may urge mask makers to apply e-beam proximity effect correction (PEC), even more than a decrease in the reticle magnification from 5x to 4x (and further) would. For raster scan e-beams, which are typically used in mask making, correction by dose variation is not practical. Hence, PEC for these systems must be tackled by modifying the geometry of the design, in a way similar to OPC techniques. Both corrections must compromise between the accuracy achieved, which is dominated by the selected (correction and exposure) grid size, and the resulting throughput loss, caused by the use of a smaller grid size. Sigma-C now introduces a new algorithm, which enables the proximity effect correction by shape variation. It is included into CAPROX and supports hierarchy in the same manner as the other postprocessing operations. The exposure of the shape corrected pattern on a raster scan machine requires only one beam pass, whereas dose variation would require one pass for each dose. Exposures were made at IMEC and at Compugraphics. The first results on Leica EBMF10.5 and MEBES III are promising. The pure shape correction increases the line width uniformity and opens the process window for critical dimensions below 1 micrometers . Performance measurements show that the 64 Mb DRAM is a job of a few hours.

  13. Does spatial proximity drive norovirus transmission during outbreaks in hospitals?

    PubMed Central

    Harris, John P; Lopman, Ben A; Cooper, Ben S; O'Brien, Sarah J

    2013-01-01

    Objective To assess the role of spatial proximity, defined as patients sharing bays, in the spread of norovirus during outbreaks in hospitals. Design Enhanced surveillance of norovirus outbreaks between November 2009 and November 2011. Methods Data were gathered during 149 outbreaks of norovirus in hospital wards from five hospitals in two major cities in England serving a population of two million. We used the time between the first two cases of each outbreak to estimate the serial interval for norovirus in this setting. This distribution and dates of illness onset were used to calculate epidemic trees for each outbreak. We then used a permutation test to assess whether proximity, for all outbreaks, was more extreme than would be expected by chance under the null hypothesis that proximity was not associated with transmission risk. Results 65 outbreaks contained complete data on both onset dates and ward position. We estimated the serial interval to be 1.86 days (95% CI 1.6 to 2.2 days), and with this value found strong evidence to reject the null hypothesis that proximity was not significant (p<0.001). Sensitivity analysis using different values of the serial interval showed that there was evidence to reject the null hypothesis provided the assumed serial interval was less than 2.5 days. Conclusions Our results provide evidence that patients occupying the same bay as patients with symptomatic norovirus infection are at an increased risk of becoming infected by these patients compared with patients elsewhere in the same ward. PMID:23852138

  14. Gate-controlled superconducting proximity effect in ultrathin graphite films

    NASA Astrophysics Data System (ADS)

    Sato, T.; Moriki, T.; Tanaka, S.; Kanda, A.; Goto, H.; Miyazaki, H.; Odaka, S.; Ootuka, Y.; Tsukagoshi, K.; Aoyagi, Y.

    2008-03-01

    We experimentally investigated electrical transport in thin graphite films about 10 nm thick connected to superconducting leads. Proximity-induced superconductivity was observed and the critical supercurrent strongly depends on the gate voltage. From the maximum-to-minimum ratios of the critical supercurrent and the normal state resistance, we conclude that the major part of the supercurrent flows in a few graphene layers close to the gate electrode.

  15. Proximal humerus shaft fracture after pectoralis major tendon rupture repair.

    PubMed

    Silverstein, Jeff A; Goldberg, Ben; Wolin, Preston

    2011-06-01

    Surgical repair of a complete pectoralis major tendon rupture at the humeral insertion has superior results compared to nonoperative treatment. To our knowledge, a proximal humerus shaft fracture occurring at the site of the bone trough and cortical drill holes after a pectoralis major tendon rupture repair has not been reported in the literature.A 45-year-old man sustained an acute left pectoralis major tendon rupture at the humeral insertion while performing a bench press maneuver. He underwent acute surgical repair. Approximately 8 weeks postoperatively, the patient fell from a standing height and sustained a proximal humerus shaft fracture through the repair site at the bone trough. Three days after the fracture, the patient underwent open reduction and internal fixation of the proximal humerus shaft fracture and exploration of the pectoralis major tendon repair. The fracture was found to be at the level of the repair site, and the pectoralis major tendon was completely intact to the distal fragment. The fracture healed uneventfully, and the patient regained full motion and strength of his extremity with no limitations.Any type of surgical fixation that creates a hole in the humerus or decreases the cross-sectional area such as a bone trough creates a stress riser. Patients undergoing pectoralis tendon repair that involves violating the humerus with a bone trough or hole have a slight risk of postoperative humerus fracture, especially if sustaining an early traumatic event such as a fall. PMID:21667914

  16. Effects of Hip Geometry on Fracture Patterns of Proximal Femur

    PubMed Central

    Kazemi, Seyyed Morteza; Qoreishy, Mohamad; Keipourfard, Ali; Sajjadi, Mohammadreza Minator; Shokraneh, Shahram

    2016-01-01

    Background: Some studies have previously shown that geometry of proximal femur can affect the probability of fracture and type of fracture. It happens since the geometry of the proximal femur determines how a force is applied to its different parts. In this study, we have compared proximal femur’s geometric characteristics in femoral neck (FNF), intertrochanteric (ITF) and Subtrochanteric (STF) fractures. Methods: In this study, 60 patients who had hip fractures were studied as case studies. They were divided into FNF, ITF and STF groups based on their fracture types (20 patients in each group). Patients were studied with x-ray radiography and CT scans. Radiological parameters including femoral neck length from lateral cortex to center of femoral head (FNL), diameter of femoral head (FHD), diameter of femoral neck (FND), femoral head neck offset (FHNO), neck-shaft angle (alpha), femoral neck anteversion (beta) were measured and compared in all three groups. Results: Amount of FNL was significantly higher in STF group compared to FNF (0.011) while ITF and STF as well as FNT and ITF did not show a significant different. Also, FND in FNF group was significantly lower than the other two groups, i.e. ITF and STF. In other cases there were no instances of significant statistical difference. Conclusion: Hip geometry can be used to identify individuals who are at the risk of fracture with special pattern. Also, it is important to have more studies in different populations and more in men. PMID:27517071

  17. Proximal femur segmentation in conventional pelvic x ray.

    PubMed

    Pilgram, Roland; Walch, Claudia; Kuhn, Volker; Schubert, Rainer; Staudinger, Roland

    2008-06-01

    A solid and accurate proximal femur segmentation technique using the popular active shape model (ASM) is proposed. For generating an optimal shape prior, the minimum description length, based on 200 supervised manual segmented proximal femur shapes, is used. The segmentation is based on a coarse to fine scaling technique including a profile scale space method. The segmentation results are compared using an optimal defined initial pose and a pose based on a registration technique. Using ideal template initialization, 95% of the shapes have been recovered exactly (average point-to-point error approximately 13 pixels, average point-to-boundary error approximately 7 pixels). Using a template-based initialization based on a registration technique, a successful segmentation rate of approximately 89% is achieved, with an average point-to-point error approximately 12 pixels, and an average point-to-boundary error approximately 8 pixels. With an adequate template initialization and an improved ASM, this method seems to provide an accurate tool for segmentation of the proximal femur shapes on conventional hip overview x-ray images. PMID:18649479

  18. The role of physical proximity in nosocomial diarrhea.

    PubMed

    Chang, V T; Nelson, K

    2000-09-01

    To examine physical proximity as a risk factor for the nosocomial acquisition of Clostridium difficile-associated diarrhea (CDAD) and of antibiotic-associated diarrhea (AAD), we assessed a retrospective cohort of 2859 patients admitted to a community hospital from 1 March 1987 through 31 August 1987. Of these patients, 68 had nosocomial CDAD and 54 had nosocomial AAD. In multivariate analysis, physical proximity to a patient with CDAD (relative risk [RR], 1.86; 95% confidence interval [CI], 1.06-3.28), exposure to clindamycin (RR, 4.22; 95% CI, 2.11-8.45), and the number of antibiotics taken (RR, 1.49; 95% CI, 1.23-1.81) were significant. For patients with nosocomial AAD, exposure to a roommate with AAD (RR, 3.94; 95% CI, 1. 27-12.24), a stay in an intensive care unit or cardiac care unit (RR, 1.93; 95% CI, 1.05-3.53), and the number of antibiotics taken (RR, 2.01; 95% CI, 1.67-2.40) were significant risk factors. Physical proximity may be an independent risk factor for acquisition of nosocomial CDAD and AAD. PMID:11017821

  19. Mechanosensory function of microvilli of the kidney proximal tubule

    PubMed Central

    Du, Zhaopeng; Duan, Yi; Yan, QingShang; Weinstein, Alan M.; Weinbaum, Sheldon; Wang, Tong

    2004-01-01

    Normal variations in glomerular filtration induce proportional changes in proximal tubule Na+ reabsorption. This “glomerulotubular balance” derives from flow dependence of Na+ uptake across luminal cell membranes; however, the underlying physical mechanism is unknown. Our hypothesis is that flow-dependent reabsorption is an autoregulatory mechanism that is independent of neural and hormonal systems. It is signaled by the hydrodynamic torque (bending moment) on epithelial microvilli. Such signals need to be transmitted to the terminal web to modulate Na+-H+-exchange activity. To investigate this hypothesis, we examined Na+ transport and tubular diameter in response to different flow rates during the microperfusion of isolated S2 proximal tubules from mouse kidneys. The data were analyzed by using a mathematical model to estimate the microvillous torque as function of flow. In this model, increases in luminal diameter have the effect of blunting the impact of flow velocity on microvillous shear stress and, thus, microvillous torque. We found that variations in microvillous torque produce nearly identical fractional changes in Na+ reabsorption. Furthermore, the flow-dependent Na+ transport is increased by increasing luminal fluid viscosity, diminished in Na+-H+ exchanger isoform 3 knockout mice, and abolished by nontoxic disruption of the actin cytoskeleton. These data support our hypothesis that the “brush-border” microvilli serve a mechanosensory function in which fluid dynamic torque is transmitted to the actin cytoskeleton and modulates Na+ absorption in kidney proximal tubules. PMID:15319475

  20. The kinetochore prevents centromere-proximal crossover recombination during meiosis.

    PubMed

    Vincenten, Nadine; Kuhl, Lisa-Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair Rw; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L

    2015-01-01

    During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. PMID:26653857

  1. Relationships proximate analysis results and higher heating values of lignites

    SciTech Connect

    Demirbas, A.

    2008-07-01

    In this study, the higher heating values (HHVs) of 26 lignite samples were calculated by using the proximate and elemental analyses data. The proximate analysis results such as volatile materials (VM), fixed carbon (FC) and HHV and the elemental analysis results such as carbon, hydrogen (H), oxygen (O), nitrogen (N) and sulfur (S) were determined for 26 lignite samples from different areas of Turkey. The lignite samples have been tested with particle size of 0-0.05 mm. The HHVs of 26 lignite samples obtained from different Turkish sources were determined experimentally and calculated from both ultimate and proximate analyses. HHVs of 26 the lignite samples can be calculated from the equation based modeling. The HHVs (MJ/kg) of the lignite samples as a function of fixed carbon (FC, wt%) or volatile materials (VM, %) was calculated from the following equations: HHV = 0.300FC + 11.117 (1) HHV = -0.323VM + 42.223 (2) where the correlation coefficients for Eqs. (1) and (2) were 0.9907 and 0.9862, respectively. The combustion heats calculated from Eqs. (1) and (2) showed mean differences of +3.9% and +0.3%, respectively. The HHVs (MJ/kg) of the lignite samples as a function of C, H, O, N, and S were calculated from a given equation where the correlation coefficients for the equation was 0.9891. HHVs calculated from this equation showed a mean deviation of +0.1.

  2. Proximity corrected accurate in-die registration metrology

    NASA Astrophysics Data System (ADS)

    Daneshpanah, M.; Laske, F.; Wagner, M.; Roeth, K.-D.; Czerkas, S.; Yamaguchi, H.; Fujii, N.; Yoshikawa, S.; Kanno, K.; Takamizawa, H.

    2014-07-01

    193nm immersion lithography is the mainstream production technology for the 20nm and 14nm logic nodes. Multi-patterning of an increasing number of critical layers puts extreme pressure on wafer intra-field overlay, to which mask registration error is a major contributor [1]. The International Technology Roadmap for Semiconductors (ITRS [2]) requests a registration error below 4 nm for each mask of a multi-patterning set forming one layer on the wafer. For mask metrology at the 20nm and 14nm logic nodes, maintaining a precision-to-tolerance (P/T) ratio below 0.25 will be very challenging. Full characterization of mask registration errors in the active area of the die will become mandatory. It is well-known that differences in pattern density and asymmetries in the immediate neighborhood of a feature give rise to apparent shifts in position when measured by optical metrology systems, so-called optical proximity effects. These effects can easily be similar in magnitude to real mask placement errors, and uncorrected can result in mis-qualification of the mask. Metrology results from KLA-Tencor's next generation mask metrology system are reported, applying a model-based algorithm [3] which includes corrections for proximity errors. The proximity corrected, model-based measurements are compared to standard measurements and a methodology presented that verifies the correction performance of the new algorithm.

  3. Glutamatergic Signaling Maintains the Epithelial Phenotype of Proximal Tubular Cells

    PubMed Central

    Bozic, Milica; de Rooij, Johan; Parisi, Eva; Ortega, Marta Ruiz; Fernandez, Elvira

    2011-01-01

    Epithelial–mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrangement in cells of the central nervous system, but whether it helps maintain the epithelial phenotype of the proximal tubule is unknown. Here, knockdown of NMDAR1 in a proximal tubule cell line (HK-2) induced changes in cell morphology, reduced E-cadherin expression, and increased α-SMA expression. Induction of EMT with TGF-β1 led to downregulation of both E-cadherin and membrane-associated β-catenin, reorganization of F-actin, expression of mesenchymal markers de novo, upregulation of Snail1, and increased cell migration; co-treatment with NMDA attenuated all of these changes. Furthermore, NMDA reduced TGF-β1–induced phosphorylation of Erk1/2 and Akt and the activation of Ras, suggesting that NMDA antagonizes TGF-β1–induced EMT by inhibiting the Ras-MEK pathway. In the unilateral ureteral obstruction model, treatment with NMDA blunted obstruction-induced upregulation of α-SMA, FSP1, and collagen I and downregulation of E-cadherin. Taken together, these results suggest that NMDAR plays a critical role in preserving the normal epithelial phenotype and modulating tubular EMT. PMID:21597037

  4. Risk factors and predictors of mortality for proximal humeral fractures

    PubMed Central

    Gooding, Benjamin WT; Manning, Paul A; Wallace, W Angus; Geoghegan, John M

    2014-01-01

    Background Risk factors for mortality after proximal humeral fracture, including socioeconomic status, are poorly defined. This retrospective review of prospectively collected data defines the epidemiology and predictors of mortality in association with proximal humeral fractures. Methods Patients who sustained proximal humeral fractures were identified from fragility fracture and trauma databases between May 2001 and September 2012. Results In total, 1880 patients with a mean age of 69 years and a male to female ratio of 2 : 3 were identified. Socioeconomic distribution is skewed towards the lowest and highest quintiles. Low-energy mechanisms caused 88% of fractures. Men sustain fractures when they are aged 10 years younger and via higher-energy mechanisms. In total, 536 patients (29%) died within the study period with a 1-year mortality of 9.8%, rising to 28.2% at 5 years. Female gender, increasing age, pathological fracture and increased number of co-morbidities were independent variables for increased mortality. Conclusions The present study, which was conducted over an 11-year period, is the first to combine the epidemiology and risk factors for mortality with socioeconomic rank. One-year mortality risk is twice that of the background matched population. Patient counselling with respect to increased mortality should be considered, especially in higher-risk elderly females with multiple co-morbidities.

  5. The kinetochore prevents centromere-proximal crossover recombination during meiosis

    PubMed Central

    Vincenten, Nadine; Kuhl, Lisa-Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair RW; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L

    2015-01-01

    During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10850.001 PMID:26653857

  6. Thrust Characteristics of Multiple Lifting Jets in Ground Proximity

    NASA Technical Reports Server (NTRS)

    Davenport, Edwin E.; Spreeman, Kenneth P.

    1960-01-01

    An investigation has been made to determine the thrust characteristics within ground proximity of a series of models which might represent vertical take-off-and-landing (VTOL) aircraft with multiple exit jet engines exhausting vertically downward beneath a lifting surface. Variations in simulated engine configurations were provided by a series of nozzle insert plugs in which the number of jet exits, located symmetrically on a fixed circle, was varied, or the diameter of the circle was varied for a given number of jet exits. represent lifting surfaces, and high-pressure air was used to simulate jet-engine exhaust. Plywood plates were used to The results of the investigation showed that increasing the number of exits, such that an annular jet configuration was approached, provided more favorable thrust characteristics within ground proximity than any other variation in the geometry of these multiple jets. Tests of a configuration with two nozzles approximating a fan-in-wing VTOL aircraft with fans located at different spanwise locations indicated that the augmentation in thrust within ground proximity was greater for the arrangement with the more inboard location of the nozzles.

  7. Proximity interactions among centrosome components identify regulators of centriole duplication.

    PubMed

    Firat-Karalar, Elif Nur; Rauniyar, Navin; Yates, John R; Stearns, Tim

    2014-03-17

    The centrosome consists of a pair of centrioles and surrounding pericentriolar material (PCM). Many vertebrate cells also have an array of granules, termed centriolar satellites, that localize around the centrosome and are associated with centrosome and cilium function. Centriole duplication occurs once per cell cycle and is effected by a set of proteins including PLK4, CEP192, CEP152, CEP63, and CPAP. Information on the relationships between these components is limited due to the difficulty in assaying interactions in the context of the centrosome. Here, we used proximity-dependent biotin identification (BioID) to identify proximity interactions among centriole duplication proteins. PLK4, CEP192, and CEP152 BioID identified known physically interacting proteins and a new interaction between CEP152 and CDK5RAP2 consistent with a function of CEP152 in PCM recruitment. BioID for CEP63 and its paralog CCDC67 revealed extensive proximity interactions with centriolar satellite proteins. Focusing on these satellite proteins identified two new regulators of centriole duplication, CCDC14 and KIAA0753. Both proteins colocalize with CEP63 to satellites, bind to CEP63, and identify other satellite proteins by BioID. KIAA0753 positively regulates centriole duplication and CEP63 centrosome localization, whereas CCDC14 negatively regulates both processes. These results suggest that centriolar satellites have a previously unappreciated function in regulating centriole duplication. PMID:24613305

  8. Proximate and elemental analyses of Tinospora cordifolia stem.

    PubMed

    Mahima; Rahal, Anu; Prakash, Atul; Verma, Amit Kumar; Kumar, Vinod; Roy, Debashish

    2014-05-01

    Tinospora cordifolia also known as Giloy or Guduchi, is an indigenous climber plant indigenous to tropical areas of India, Myanmar and Sri Lanka. Its stem is used for treatment of fever, jaundice, emaciation, skin ailments, diabetes, anaemia and various infectious diseases. The study was undertaken to evaluate the proximate and elemental analysis of the stems of Tinospora cordifolia. The proximate analyses were carried out using standard methods, while mineral elements were analyzed using Atomic Absorption Spectrophotometer, equipped with air acetylene flame. The proximate analysis of the stems of Tinospora cordifolia showed that it contained moisture 34.39%, ether extract 0.912%, crude protein 7.74%, crude fibre 56.42%, total ash 7.96%, nitrogen free extract 26.97%, cellulose 23.02% and hemicellulose 3.70%. The mineral analysis of the stems showed that they contain the following essential minerals: Calcium (102.23 ppm), phosphorous (24.81 ppm), iron (26.058 ppm), copper (3.733 ppm), zinc (7.342 ppm) and manganese (12.242 ppm). The study revealed that Tinospora cordifolia stems to be a potential source of nutrition and minerals for man as well as animals. PMID:26031012

  9. Proximal femur segmentation in conventional pelvic x ray

    SciTech Connect

    Pilgram, Roland; Walch, Claudia; Kuhn, Volker; Schubert, Rainer; Staudinger, Roland

    2008-06-15

    A solid and accurate proximal femur segmentation technique using the popular active shape model (ASM) is proposed. For generating an optimal shape prior, the minimum description length, based on 200 supervised manual segmented proximal femur shapes, is used. The segmentation is based on a coarse to fine scaling technique including a profile scale space method. The segmentation results are compared using an optimal defined initial pose and a pose based on a registration technique. Using ideal template initialization, 95% of the shapes have been recovered exactly (average point-to-point error {approx}13 pixels, average point-to-boundary error {approx}7 pixels). Using a template-based initialization based on a registration technique, a successful segmentation rate of {approx}89% is achieved, with an average point-to-point error {approx}12 pixels, and an average point-to-boundary error {approx}8 pixels. With an adequate template initialization and an improved ASM, this method seems to provide an accurate tool for segmentation of the proximal femur shapes on conventional hip overview x-ray images.

  10. Superconducting proximity effect in InAs nanowires

    NASA Astrophysics Data System (ADS)

    Chang, Willy

    First discovered by Holm and Meissner in 1932, the superconducting proximity effect has remained a subject of experimental and theoretical interest. In recent years, it has been proposed that proximity effect in a semiconductor with large g-factor and spin-orbit coupling could lead to exotic phases of superconductivity. This thesis focuses on proximity effect in one of the prime semiconductor candidates---InAs nanowires. The first set of experiments investigates the superconducting phase-dependent tunneling spectrum of a proximitized InAs quantum dot. We observe tunneling resonances of Andreev bound states in the Kondo regime, and induce quantum phase transitions of the quantum dot ground state with gate voltage and phase bias---the latter being the first experimental observation of its kind. An additional zero-bias peak of unknown origin is observed to coexist with the Andreev bounds states. The second set of experiments extends upon the first with sharper tunneling resonances and an increase in the device critical field. By applying an external magnetic field, we observe spin-resolved Andreev bound states in proximitized InAs quantum dots. From the linear splitting of the tunneling resonances, we extract g-factors of 5 and 10 in two different devices. The third set of experiments utilizes a novel type of epitaxial core-shell InAs-Al nanowire. We compare the induced gaps of these nanowires with control devices proximitized with evaporated Al films. Our results show that the epitaxial core-shell nanowires possess a much harder induced gap---up to two orders of magnitude in sub-gap conductance suppression as compared to a factor of five in evaporated control devices. This observation suggests that roughness in S-N interfaces plays a crucial role in the quality of the proximity effect. The fourth set of experiments investigates the gate-tunability of epitaxial half-shell nanowires. In a half-shell nanowire Josephson junction, we measure the normal state resistance

  11. Correction of proximal tibia varus with external fixation.

    PubMed

    Ashfaq, Kashif; Fragomen, Austin T; Nguyen, Joseph T; Rozbruch, S Robert

    2012-11-01

    Correction of proximal tibia varus deformity has been used with success. Our Protocol is to use monolateral frame to correct varus of less than 10 degrees and to use the Taylor spatial frame for deformities greater than 10 degrees and for multiplanar deformities. Is this protocol successful? Ninety-one limbs in 68 patients with proximal tibia varus were treated with percutaneous proximal tibial osteotomy and external fixation. The monolateral and spatial frames were used for 36 and 55 limbs, respectively. Each group was further subdivided into neutral or intentionally overcorrected subgroups. Monolateral group time of correction and time in frame was 15 days (8 to 20) and 101 days (81 to 133), respectively. The preoperative mechanical axis deviation (MAD) was 22 mm medial (10 to 44). Postoperative MAD in the neutral subgroup was 5 mm lateral (2 to 10) and 3 mm medial (0 to 7). Postoperative MAD in the overcorrected subgroup was 10 mm lateral (4 to 20) and one patient was 5 mm medial. Medial proximal tibial angle (MPTA) improved from 85 degrees (79 to 89) to 90 degrees (85 to 96) in the neutral group and to 92 degrees (85 to 98) in the overcorrected group. Spatial frame group time of correction and time in frame was 34 days (7 to 99) and 130 days (95 to 177), respectively. The preoperative MAD was 40 mm medial (range 5 to 155). This improved to 5 mm medial (0 to 30) and 4 mm lateral (0 to 7) in the neutral group, and 17 mm medial (0 to 35) and 11 mm lateral (4 to 28) in the overcorrection group. MPTA improved from 80 degrees (40 to 87) to 88 degrees (83 to 96) in the neutral group and to 84 degrees (89 to 97) in the overcorrected group. In both groups, there was no significant change in the ankle or knee range of motion. There was one refracture in both groups. Our algorithm for treating proximal tibial varus deformities is safe and effective. For simple varus deformities, we recommend use of the monolateral frame. We reserve the use of the spatial frame for large

  12. [Multidimensional corrective osteotomy of the proximal femur using the gamma-nail].

    PubMed

    Moeller, K; Wich, M; Letsch, R

    1998-04-01

    We report on a 57-year-old patient suffering from a complex malposition of proximal femur after osteosynthesis using a condylar plate. For polyaxial correction of the proximal femur we successfully used an intramedullary hip screw system. PMID:9613218

  13. Regulation of a bovine nonclassical major histocompatibility complex class I gene promoter.

    PubMed

    O'Gorman, Grace M; Al Naib, Abdullah; Naib, Abdullah Al; Ellis, Shirley A; Mamo, Solomon; O'Doherty, Alan M; Lonergan, Pat; Fair, Trudee

    2010-08-01

    Studies have shown in humans and other species that the major histocompatibility complex class I (MHC-I) region is involved at a number of levels in the establishment and maintenance of pregnancy. The aim of this study was to characterize how a bovine nonclassical MHC-I gene (NC1) is regulated. Initial serial deletion experiments of a 2-kb fragment of the NC1 promoter identified regions with positive regulatory elements in the proximal promoter and evidence for a silencer module(s) further upstream that cooperatively contributed to constitutive NC1 expression. The cytokines interferon tau (IFNT), interferon gamma (IFNG), and interleukin 4 (IL4) significantly increased luciferase expression in NC1 promoter reporter constructs and endogenous NC1 mRNA levels in a bovine endometrial cell line. In addition, IFNG, IL3, IL4, and progesterone significantly increased Day 7 bovine blastocyst NC1 mRNA expression when supplemented during in vitro embryo culture. Site-directed mutagenesis analysis identified a STAT6 binding site that conferred IL4 responsiveness in the NC1 proximal promoter. Furthermore, methylation treatment of the proximal promoter, which contains a CpG island, completely abrogated constitutive NC1 expression. Overall, the findings presented here suggest that constitutive NC1 expression is regulated positively by elements in the proximal promoter, which are further controlled by upstream silencer modules. The promoter is responsive to IFNT, IFNG, and IL4, suggesting possible roles for these cytokines in bovine preimplantation embryo survival and/or maternal-fetal tolerance. Our studies also suggest that methylation of the proximal promoter, in particular, could play a significant role in regulating NC1 expression. PMID:20427761

  14. Twist to matricing: Restoration of adjacent proximal defects in a novel manner

    PubMed Central

    Chhabra, Naveen; Gyanani, Hitesh; Rathore, Vishnu Pratap Singh; Shah, Purnil

    2016-01-01

    The quality treatment in an efficient way is the road map to successful clinical practice. Various methods are employed to achieve goals. Refurbishment of the adequate marginal ridge, proximal contact, and contour are the prime challenges in restoring two adjacent proximal defects. This paper presents an overview of achieving satisfactory proximal restorations in a time saving innovative manner. PMID:26958530

  15. Proximal tibiofibular synostosis as a possible cause of a pseudoradicular syndrome: a case report.

    PubMed

    van Ooij, Bas; van Ooij, André; Morrenhof, J Wim; van Dijk, C Niek

    2011-12-01

    This paper presents a case report of persistent low back pain and suspected lumbar radiculopathy. A synostosis at the level of the proximal tibiofibular joint was diagnosed. After successful resection of the synostosis, the low back symptoms resolved completely. This is the first report of a proximal tibiofibular synostosis as a possible cause of referred pain proximally. PMID:21222100

  16. Conservation of sigma–core RNA polymerase proximity relationships between the enhancer-independent and enhancer-dependent sigma classes

    PubMed Central

    Wigneshweraraj, Siva R.; Fujita, Nobuyuki; Ishihama, Akira; Buck, Martin

    2000-01-01

    Two distinct classes of RNA polymerase sigma factors (σ) exist in bacteria and are largely unrelated in primary amino acid sequence and their modes of transcription activation. Using tethered iron chelate (Fe-BABE) derivatives of the enhancer-dependent σ54, we mapped several sites of proximity to the β and β′ subunits of the core RNA polymerase. Remarkably, most sites localized to those previously identified as close to the enhancer-independent σ70 and σ38. This indicates a common use of sets of sequences in core for interacting with the two σ classes. Some sites chosen in σ54 for modification with Fe-BABE were positions, which when mutated, deregulate the σ54–holoenzyme and allow activator-independent initiation and holoenzyme isomerization. We infer that these sites in σ54 may be involved in interactions with the core that contribute to maintenance of alternative states of the holoenzyme needed for either the stable closed promoter complex conformation or the isomerized holoenzyme conformation associated with the open promoter complex. One site of σ54 proximity to the core is apparently not evident with σ70, and may represent a specialized interaction. PMID:10856247

  17. Mis-regulation of Mammalian Target of Rapamycin (mTOR) Complexes Induced by Albuminuria in Proximal Tubules*

    PubMed Central

    Peruchetti, Diogo B.; Cheng, Jie; Caruso-Neves, Celso; Guggino, William B.

    2014-01-01

    High albumin concentrations in the proximal tubule of the kidney causes tubulointerstitial injury, but how this process occurs is not completely known. To address the signal transduction pathways mis-regulated in renal injury, we studied the modulation of mammalian target of rapamycin (mTOR) complexes by physiologic and pathophysiologic albumin concentrations in proximal tubule cells. Physiologic albumin concentrations activated the PI3K/mTORC2/PKB/mTORC1/S6 kinase (S6K) pathway, but pathophysiologically high albumin concentrations overactivated mTORC1 and inhibited mTORC2 activity. This control process involved the activation of ERK1/2, which promoted the inhibition of TSC2 and activation of S6K. Furthermore, S6K was crucial to promoting the over activation of mTORC1 and inhibition of mTORC2. Megalin expression at the luminal membrane is reduced by high concentrations of albumin. In addition, knockdown of megalin mimicked all the effects of pathophysiologic albumin concentrations, which disrupt normal signal transduction pathways and lead to an overactivation of mTORC1 and inhibition of mTORC2. These data provide new perspectives for understanding the molecular mechanisms behind the effects of albumin on the progression of renal disease. PMID:24790108

  18. Osmotic diuresis in a mathematical model of the rat proximal tubule.

    PubMed

    Weinstein, A M

    1986-05-01

    Solute reabsorption in the presence of an osmotic load has been examined in a model of the rat proximal convoluted tubule. The model is a computer simulation of a 0.5-cm segment of tubule comprised of compliant cellular and paracellular compartments, which tracks the luminal profiles of Na, K, Cl, HCO3, phosphate, glucose, and urea. In one series of calculations, the peritubular and initial luminal glucose concentrations are varied from 1.0 to 50 mmol/liter. The resulting proximal reabsorption of glucose increases monotonically to 1.5 nmol X s-1 X cm-2. Sodium reabsorption increases with glucose perfusion concentrations between 1.0 and 10 mmol/liter and then declines with greater glucose loads. Above 10 mmol/liter glucose, there is progressive decline in mean luminal Na concentration so that diffusive paracellular backflux, as well as decreased convective reabsorption, are responsible for the natriuresis. Diuresis per se blunts reabsorption of species requiring the development of lumen-to-bath concentration gradients (i.e., K, Cl, and urea). Diminished bicarbonate reabsorption is also predicted with large glucose loads due to intraepithelial alkalinization. This derives both from cellular depolarization and bicarbonate trapping (interspace closure). It is also observed that when interspace closure occurs, a region of intraepithelial K depletion may be formed, promoting diffusive reabsorption of potassium across the tight junction. Thus a 'middle compartment model' for potassium may provide a means of achieving tubule fluid-to-plasma K ratios less than 1.0, in the absence of specific cellular uptake mechanisms. PMID:3706538

  19. Bcl-2–Modifying Factor Induces Renal Proximal Tubular Cell Apoptosis in Diabetic Mice

    PubMed Central

    Lau, Garnet J.; Godin, Nicolas; Maachi, Hasna; Lo, Chao-Sheng; Wu, Shyh-Jong; Zhu, Jian-Xin; Brezniceanu, Marie-Luise; Chénier, Isabelle; Fragasso-Marquis, Joelle; Lattouf, Jean-Baptiste; Ethier, Jean; Filep, Janos G.; Ingelfinger, Julie R.; Nair, Viji; Kretzler, Matthias; Cohen, Clemens D.; Zhang, Shao-Ling; Chan, John S.D.

    2012-01-01

    This study investigated the mechanisms underlying tubular apoptosis in diabetes by identifying proapoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RPTCs) in models of diabetes. Total RNAs isolated from renal proximal tubules (RPTs) of 20-week-old heterozygous db/m+, db/db, and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real-time quantitative PCR assays, immunohistochemistry, and mice rendered diabetic with streptozotocin were used to validate the proapoptotic gene expression in RPTs. Cultured rat RPTCs were used to confirm the apoptotic activity and regulation of proapoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were used to confirm enhanced proapoptotic gene expression in RPTs. Bcl-2–modifying factor (Bmf) was differentially upregulated (P < 0.01) in RPTs of db/db mice compared with db/m+ and db/db CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs coimmunoprecipated with Bcl-2, enhanced caspase-3 activity, and promoted apoptosis. High glucose (25 mmol/L) induced Bmf mRNA expression in RPTCs, whereas rotenone, catalase, diphenylene iodinium, and apocynin decreased it. Knockdown of Bmf with small interfering RNA reduced high glucose–induced apoptosis in RPTCs. More important, enhanced Bmf expression was detected in RPTs of kidneys from patients with diabetes. These data demonstrate differential upregulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes. PMID:22210314

  20. NHE3 Regulatory Factor 1 (NHERF1) Modulates Intestinal Sodium-dependent Phosphate Transporter (NaPi-2b) Expression in Apical Microvilli*

    PubMed Central

    Giral, Hector; Cranston, DeeAnn; Lanzano, Luca; Caldas, Yupanqui; Sutherland, Eileen; Rachelson, Joanna; Dobrinskikh, Evgenia; Weinman, Edward J.; Doctor, R. Brian; Gratton, Enrico; Levi, Moshe

    2012-01-01

    Pi uptake in the small intestine occurs predominantly through the NaPi-2b (SLC34a2) co-transporter. NaPi-2b is regulated by changes in dietary Pi but the mechanisms underlying this regulation are largely undetermined. Sequence analyses show NaPi-2b has a PDZ binding motif at its C terminus. Immunofluorescence imaging shows NaPi-2b and two PDZ domain containing proteins, NHERF1 and PDZK1, are expressed in the apical microvillar domain of rat small intestine enterocytes. Co-immunoprecipitation studies in rat enterocytes show that NHERF1 associates with NaPi-2b but not PDZK1. In HEK co-expression studies, GFP-NaPi-2b co-precipitates with FLAG-NHERF1. This interaction is markedly diminished when the C-terminal four amino acids are truncated from NaPi-2b. FLIM-FRET analyses using tagged proteins in CACO-2BBE cells show a distinct phasor shift between NaPi-2b and NHERF1 but not between NaPi-2b and the PDZK1 pair. This shift demonstrates that NaPi-2b and NHERF1 reside within 10 nm of each other. NHERF1−/− mice, but not PDZK1−/− mice, had a diminished adaptation of NaPi-2b expression in response to a low Pi diet. Together these studies demonstrate that NHERF1 associates with NaPi-2b in enterocytes and regulates NaPi-2b adaptation. PMID:22904329

  1. Effect of proximal and distal venting during intramedullary nailing.

    PubMed

    Martin, R; Leighton, R K; Petrie, D; Ikejiani, C; Smyth, B

    1996-11-01

    During intramedullary manipulation, 2 main phenomena occur. A dramatic rise in intramedullary pressure occurs followed by intravasation of damaged marrow tissue. There are concerns about the development of increased interosseous pressure during reaming and the potential for this to contribute to fat embolism syndrome. The intramedullary pressures generated with various intramedullary devices was determined and the effects of a fracture, with and without proximal and distal venting on these pressures were studied. Pressures generated in 78 embalmed anatomic specimen femurs and tibias were studied, leaving all soft tissues intact. Pressures were recorded for awl, guide rod, reamer, and nail insertion. Venting was done by creating a 4.5-mm hole in the cortex directly opposite the transducer. Proximal venting reduced proximal pressures to 80 mm Hg in the tibia (90% reduction) and 460 mm Hg in the femur (70% reduction). Distal venting reduced distal pressures to 65 mm and 30 mm in the tibias and femurs, respectively (90% reduction in pressures). Intramedullary pressures generated during nail or alignment rod insertion in anatomic specimen bone greatly exceeds the critical thresholds (150 mm Hg) thought to be responsible for fat emboli to the lung in the dogs. The introduction of a vent may reduce the chance of fat embolism. Despite the high association of raised intramedullary pressures and fat emboli in animal studies, there is no known critical threshold for humans. Therefore, although venting seems effective in reducing the intramedullary pressure in anatomic specimen bones, its efficacy in the patient with trauma remains to be determined. PMID:8913148

  2. Proximity Effects and Nonequilibrium Superconductivity in Transition-Edge Sensors

    NASA Technical Reports Server (NTRS)

    Sadleir, John E.; Smith, Stephen J.; Robinson, Ian K.; Finkbeiner, Fred M.; Chervenak, James A.; Bandler, Simon R.; Eckart, Megan E.; Kilbourne, Caroline A.

    2011-01-01

    We have recently shown that normal-metal/superconductor (N/S) bilayer TESs (superconducting Transition-Edge Sensors) exhibit weak-link behavior.l Here we extend our understanding to include TESs with added noise-mitigating normal-metal structures (N structures). We find TESs with added Au structures also exhibit weak-link behavior as evidenced by exponential temperature dependence of the critical current and Josephson-like oscillations of the critical current with applied magnetic field. We explain our results in terms of an effect converse to the longitudinal proximity effect (LoPE) 1, the lateral inverse proximity effect (LaiPE), for which the order parameter in the N/S bilayer is reduced due to the neighboring N structures. Resistance and critical current measurements are presented as a function of temperature and magnetic field taken on square Mol Au bilayer TESs with lengths ranging from 8 to 130 {\\mu}m with and without added N structures. We observe the inverse proximity effect on the bilayer over in-plane distances many tens of microns and find the transition shifts to lower temperatures scale approximately as the inverse square of the in- plane N-structure separation distance, without appreciable broadening of the transition width. We also present evidence for nonequilbrium superconductivity and estimate a quasiparticle lifetime of 1.8 \\times 10-10 s for the bilayer. The LoPE model is also used to explain the increased conductivity at temperatures above the bilayer's steep resistive transition.

  3. Roadway Proximity and Risk of Sudden Cardiac Death in Women

    PubMed Central

    Hart, Jaime E; Chiuve, Stephanie E; Laden, Francine; Albert, Christine M

    2015-01-01

    Background Sudden cardiac death (SCD) is a major source of mortality and is the first manifestation of heart disease for the majority of cases. Thus, there is a definite need to identify risk factors for SCD that can be modified on the population level. Exposure to traffic, measured by residential roadway proximity, has been shown to be associated with an increased risk of cardiovascular disease. Our objective was to determine if roadway proximity was associated with an increased risk of SCD and to compare to the risk of other coronary heart disease (CHD) outcomes. Methods and Results A total of 523 cases of SCD were identified over 26 years of follow-up among 107,130 members of the prospective Nurses’ Health Study. We calculated residential distance to roadways at all residential addresses from 1986–2012. In age- and race-adjusted models, women living within 50 meters of a major roadway had an elevated risk of SCD (HR=1.56; 95%CI: 1.18–2.05). The association was attenuated but still statistically significant after controlling for potential confounders and mediators (HR=1.38; 95%CI:1.04–1.82). The equivalent adjusted HRs for nonfatal myocardial infarction and fatal CHD were 1.08 (95%CI: 0.96–1.23) and 1.24 (95%CI: 1.03–1.50), respectively. Conclusions Among this sample of middle-aged and older women, roadway proximity was associated with an elevated and statistically significant risks of SCD and fatal CHD, even after controlling for other cardiovascular risk factors. PMID:25332277

  4. Lithographic process window optimization for mask aligner proximity lithography

    NASA Astrophysics Data System (ADS)

    Voelkel, Reinhard; Vogler, Uwe; Bramati, Arianna; Erdmann, Andreas; Ünal, Nezih; Hofmann, Ulrich; Hennemeyer, Marc; Zoberbier, Ralph; Nguyen, David; Brugger, Juergen

    2014-03-01

    We introduce a complete methodology for process window optimization in proximity mask aligner lithography. The commercially available lithography simulation software LAB from GenISys GmbH was used for simulation of light propagation and 3D resist development. The methodology was tested for the practical example of lines and spaces, 5 micron half-pitch, printed in a 1 micron thick layer of AZ® 1512HS1 positive photoresist on a silicon wafer. A SUSS MicroTec MA8 mask aligner, equipped with MO Exposure Optics® was used in simulation and experiment. MO Exposure Optics® is the latest generation of illumination systems for mask aligners. MO Exposure Optics® provides telecentric illumination and excellent light uniformity over the full mask field. MO Exposure Optics® allows the lithography engineer to freely shape the angular spectrum of the illumination light (customized illumination), which is a mandatory requirement for process window optimization. Three different illumination settings have been tested for 0 to 100 micron proximity gap. The results obtained prove, that the introduced process window methodology is a major step forward to obtain more robust processes in mask aligner lithography. The most remarkable outcome of the presented study is that a smaller exposure gap does not automatically lead to better print results in proximity lithography - what the "good instinct" of a lithographer would expect. With more than 5'000 mask aligners installed in research and industry worldwide, the proposed process window methodology might have significant impact on yield improvement and cost saving in industry.

  5. Proximate composition and caloric content of eight Lake Michigan fishes

    USGS Publications Warehouse

    Rottiers, Donald V.; Tucker, Robert M.

    1982-01-01

    We measured the proximate composition (percentage lipid, water, fat-free dry material, ash) and caloric content of eight species of Lake Michigan fish: lake trout (Salvelinus namaycush), coho salmon (Oncorhynchus kisutch), lake whitefish (Coregonus clupeaformis), bloater (Coregonus hoyi), alewife (Alosa pseudoharengus), rainbow smelt (Osmerus mordax), deepwater sculpin (Myoxocephalus quadricornis), and slimy sculpin (Cottus cognatus). Except for alewives, proximate composition and caloric content did not differ significantly between males and females. And, for coho salmon, there was no significant difference in composition between fish collected in different years. Lipid and caloric content of lake trout increased directly with age. In all species examined, lipids and caloric contents were significantly lower in small, presumably immature, fish than in larger, older fish. Lipid content of lake trout, lake whitefish, and bloaters (range of means, 16-22%) was nearly 3 times higher than that of coho salmon, sculpins, rainbow smelt, and alewives (range of means, 5.2-7.0%). The mean caloric content ranged from 6.9 to 7.1 kcal/g for species high in lipids and from 5.8 to 6.3 kcal/g for species low in lipids. Although the caloric content of all species varied directly with lipid content and inversely with water content, an increase in lipid content did not always coincide with a proportional increase in caloric content when other components of fish composition were essentially unchanged. This observation suggests that the energy content of fish estimated from the proximate composition by using universal conversion factors may not necessarily be accurate.

  6. The proximate unit in Chinese handwritten character production

    PubMed Central

    Chen, Jenn-Yeu; Cherng, Rong-Ju

    2013-01-01

    In spoken word production, a proximate unit is the first phonological unit at the sublexical level that is selectable for production (O'Seaghdha et al., 2010). The present study investigated whether the proximate unit in Chinese handwritten character production is the stroke, the radical, or something in between. A written version of the form preparation task was adopted. Chinese participants learned sets of two-character words, later were cued with the first character of each word, and had to write down the second character (the target). Response times were measured from the onset of a cue character to the onset of a written response. In Experiment 1, the target characters within a block shared (homogeneous) or did not share (heterogeneous) the first stroke. In Experiment 2, the first two strokes were shared in the homogeneous blocks. Response times in the homogeneous blocks and in the heterogeneous blocks were comparable in both experiments (Experiment 1: 687 vs. 684 ms, Experiment 2: 717 vs. 716). In Experiment 3 and 4, the target characters within a block shared or did not share the first radical. Response times in the homogeneous blocks were significantly faster than those in the heterogeneous blocks (Experiment 3: 685 vs. 704, Experiment 4: 594 vs. 650). In Experiment 5 and 6, the shared component was a Gestalt-like form that is more than a stroke, constitutes a portion of the target character, can be a stand-alone character itself, can be a radical of another character but is not a radical of the target character (e.g., ± in , , , ; called a logographeme). Response times in the homogeneous blocks were significantly faster than those in the heterogeneous blocks (Experiment 5: 576 vs. 625, Experiment 6: 586 vs. 620). These results suggest a model of Chinese handwritten character production in which the stroke is not a functional unit, the radical plays the role of a morpheme, and the logographeme is the proximate unit. PMID:23950752

  7. STARVATION INDUCED PROXIMAL GUT MUCOSAL ATROPHY DIMINISHED WITH AGING

    PubMed Central

    Song, Juquan; Wolf, Steven E.; Wu, Xiao-Wu; Finnerty, Celeste C.; Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

    2013-01-01

    Background Starvation induces small bowel atrophy with increased intestinal epithelial apoptosis and decreased proliferation. Here, we examined these parameters after starvation in aged animals. Methods Sixty-four 6 week-old and 26 month-old C57BL/6 mice were randomly assigned to either an ad libitum fed or fasted group. The small bowel was harvested at 12, 48, and 72 hours following starvation. Proximal gut mucosal height was measured and epithelial cells counted. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Proliferation was determined by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). Comparison of fed vs. fasted and adult vs. old groups was done by one-way ANOVA with Tukey’s test and unpaired t-test. Significance was accepted at p<0.05. Results Aged mice had higher proximal gut weights, mucosal heights and cell numbers at baseline compared with the adult group (p<0.05). The rate of apoptosis was lower in the aged (p<0.05) while proliferation was not different between groups before starvation. After starvation, proximal gut wet weight decreased only in adult mice (p<0.05); Gut mucosal height and mucosal cell number decreased greater in adult than in aged mice (p<0.05). This was related to decreased proliferation only in the adult group (p<0.05). The fold of epithelial apoptosis increased was higher in the aged group than in the adult after starvation (p<0.05). Conclusions Gut mucosal kinetics change with age had lower rates of apoptosis and greater mucosal mass; the character of starvation-induced atrophy is diminished with aging. PMID:19126762

  8. The Proximate Causes of Sexual Size Dimorphism in Phrynocephalus przewalskii

    PubMed Central

    Zhao, Wei; Liu, Nai-fa

    2014-01-01

    Sexual size dimorphism (SSD) is a common phenomenon and is a central topic in evolutionary biology. Recently, the importance of pursuing an ontogenetic perspective of SSD has been emphasized, to elucidate the proximate physiological mechanisms leading to its evolution. However, such research has seldom focused on the critical periods when males and females diverge. Using mark-recapture data, we investigated the development of SSD, sex-specific survivorship, and growth rates in Phrynocephalus przewalskii (Agamidae). We demonstrated that both male and female lizards are reproductively mature at age 10–11 months (including 5 months hibernation). Male-biased SSD in snout-vent length (SVL) was only found in adults and was fully expressed at age 11 months (June of the first full season of activity), just after sexual maturation. However, male-biased SSD in tail length (TL), hind-limb length (LL), and head width (HW) were fully expressed at age 9–10 months, just before sexual maturation. Analysis of age-specific linear growth rates identified sexually dimorphic growth during the fifth growth month (age 10–11 months) as the proximate cause of SSD in SVL. The males experienced higher mortality than females in the first 2 years and only survived better than females after SSD was well developed. This suggests that the critical period of divergence in the sizes of male and female P. przewalskii occurs between 10 and 11 months of age (May to June during the first full season of activity), and that the sexual difference in growth during this period is the proximate cause. However, the sexual difference in survivorship cannot explain the male-biased SSD in SVL. Our results indicate that performance-related characteristics, such as TL, HW, and LL diverged earlier than SVL. The physiological mechanisms underlying the different growth patterns of males and females may reflect different energy allocations associated with their different reproductive statuses. PMID:24465815

  9. Percutaneous Stabilization of Impending Pathological Fracture of the Proximal Femur

    SciTech Connect

    Deschamps, Frederic Farouil, Geoffroy Hakime, Antoine Teriitehau, Christophe Barah, Ali Baere, Thierry de

    2012-12-15

    Objective: Percutaneous osteosynthesis plus cementoplasty (POPC) is a minimally invasive technique that has never been reported before and that we have prospectively evaluated for patients with impending pathological fracture of the proximal femur. Methods: We performed POPC in 12 patients (3 males, 9 females) with metastasis of the proximal femur with a high risk of fracture (Mirels' score {>=}8) between February 2010 and July 2011. Patients were not candidates for standard surgical stabilization. We analyzed the feasibility, duration, and complication of the procedure, the risk of fracture, the decrease in pain (Visual Analog Scale, VAS), and length of stay in hospital. Data were prospectively collected in all patients. Results: The mean Mirels' score was 9.8 {+-} 1.2 (range, 8-11). The technical success was 100%. POPC was performed under general anesthesia (n = 6) or conscious sedation (n = 6). The mean duration was 110 {+-} 43 (range, 60-180) minutes. All patients stood up and walked the second day after the procedure. The average length of stay in the hospital was 4 {+-} 1.6 (range, 2-7) days. We experienced two hematomas in two patients and no thromboembolic complication. For symptomatic patients (n = 8), VAS decreased from 6.5/10 (range, 2-9) before treatment to 1/10 (range, 0-3) 1 month after. No fracture occurred after a median follow-up of 145 (range, 12-608) days. Conclusions: POPC for impending pathological fracture of the proximal femur seems to be a promising alternative for cancer patients who are not candidates for surgical stabilization. Further studies are required to confirm this preliminary experience.

  10. Complications With Long Cemented Stems in Proximal Femoral Replacement.

    PubMed

    Naik, Amish A; Lietman, Steven A

    2016-05-01

    This study attempted to determine whether patients undergoing cemented long-stem proximal femoral replacement had: (1) an increased short-term mortality rate; (2) greater intraoperative hemodynamic instability; (3) a greater need for resuscitation; and (4) a decreased risk of periprosthetic fracture. The current study reviewed intraoperative and short-term events related to clinical outcomes in 24 consecutive patients who were treated at a single institution over a 5-year period. These patients underwent primary long-stem (≥250 mm, n=13) vs short-stem (<250 mm, n=11) cemented proximal femoral replacement. Other than stem length, the 2 groups were not significantly different in terms of patient age, sex, height, weight, body mass index, diagnosis, or preoperative American Society of Anesthesiologists functional score. Primary outcomes were intraoperative death, blood loss, blood transfusions, fluid resuscitation, hypotension, oxygen desaturation, mortality up to 1 year, and need for revision surgery. At 1 year, a significantly increased mortality rate (77% vs 27%, P=.03) was noted in patients receiving long-stem vs short-stem arthroplasty. Patients who received longer stems also required more intraoperative blood transfusions and fluid resuscitation (P=.04) for greater hypotension (P=.04) and oxygen desaturation (P=.04). Two intraoperative deaths occurred in the long-stem group, and none occurred in the short-stem group. The findings suggest that there is an increased risk of intraoperative hemodynamic instability with long-stem vs short-stem proximal femoral replacement, with a need for greater resuscitative efforts and an increased risk of mortality at 1 year. [Orthopedics. 2016; 39(3):e423-e429.]. PMID:27064780

  11. Ultimate Drivers and Proximate Correlates of Polyandry in Predatory Mites

    PubMed Central

    Schausberger, Peter; Patiño-Ruiz, J. David; Osakabe, Masahiro; Murata, Yasumasa; Sugimoto, Naoya; Uesugi, Ryuji; Walzer, Andreas

    2016-01-01

    Polyandry is more widespread than anticipated from Bateman’s principle but its ultimate (evolutionary) causes and proximate (mechanistic) correlates are more difficult to pinpoint than those of polygyny. Here, we combined mating experiments, quantification of reproductive traits and microsatellite genotyping to determine the fitness implications of polyandry in two predatory mite species, where males are highly polygynous (up to 45 fertilized females during life), whereas females range from monandry to various polyandry levels. The medium-level polyandrous (up to eight male mates possible) Neoseiulus californicus received clear direct and indirect benefits: multiply mated females produced more offspring with higher survival chances over longer times than singly mated females. In contrast, singly and multiply mated females of the low-level polyandrous (commonly two male mates at maximum) Phytoseiulus persimilis produced similar numbers of offspring having similar survival chances. In both species, multiple mating resulted in mixed offspring paternities, opening the chance for indirect fitness benefits such as enhanced genetic compatibility, complementarity and/or variability. However, the female re-mating likelihood and the paternity chance of non-first male mates were lower in P. persimilis than in N. californicus. Regarding proximate factors, in both species first mating duration and female re-mating likelihood were negatively correlated. Based on occasional fertilization failure of first male mates in P. persimilis, and mixed offspring paternities in both species, we argue that fertilization assurance and the chance to gain indirect fitness benefits are the ultimate drivers of polyandry in P. persimilis, whereas those of N. californicus are higher offspring numbers coupled with enhanced offspring viability and possibly other indirect fitness benefits. Overall, the adaptive significance and proximate events well reflected the polyandry levels. Our study provides

  12. CIRCUMFERENTIAL PROXIMAL FEMORAL ALLOGRAFTS IN TOTAL HIP ARTHROPLASTY REVISION SURGERY

    PubMed Central

    Roos, Bruno Dutra; Roos, Milton Valdomiro; Júnior, Antero Camisa; Lampert, Henrique Bonotto; da Silva, Matheus Luis

    2015-01-01

    Objective: To evaluate the clinical and radiographic results from patients who underwent femoral reconstruction secondary to loosening of total hip arthroplasty, using circumferential proximal femoral allografts and cemented implants. Methods: A retrospective study was conducted on 32 patients (33 hips) who underwent femoral reconstruction secondary to loosening of total hip arthroplasty, using circumferential proximal femoral allografts and cemented implants. Among these patients, 28 (29 hips) fulfilled all the requirements for this study. The mean follow-up was five years and two months. The clinical evaluation was done in accordance with the Harris Hip Score. Radiographically, the patients were assessed regarding reabsorption and consolidation of the allograft, migration of the greater trochanter, stability of the femoral component and heterotypic calcification. Results: The average preoperative Harris Hip Score was 32 points. At the last postoperative follow-up, the average score was 82 points. Allograft resorption of some degree was seen in nine hips (31%). Regarding consolidation, 24 cases (82.8%) showed full consolidation, three (10.3%) showed partial consolidation and two (6.9%) showed pseudarthrosis. All femoral components were stable. According to the criteria established, 27 cases (93.1%) were considered to be successful reconstructions after a mean follow-up of five years and two months. Conclusion: From the results obtained, it was concluded that use of circumferential proximal femoral allografts in selected cases of femoral reconstruction secondary to loosening of arthroplasty presented a high survival rate from the reconstruction over an average follow-up of five years and two months. PMID:27047896

  13. Rapid population growth and environmental degradation: ultimate versus proximate factors.

    PubMed

    Shaw, R P

    1989-01-01

    This philosophical review of 2 arguments about responsibility for and solutions to environmental degradation concludes that both sides are correct: the ultimate and the proximal causes. Ultimate causes of pollution are defined as the technology responsible for a given type of pollution, such as burning fossil fuel; proximate causes are defined as situation-specific factors confounding the problem, such as population density or rate of growth. Commoner and others argue that developed countries with low or negative population growth rates are responsible for 80% of world pollution, primarily in polluting technologies such as automobiles, power generation, plastics, pesticides, toxic wastes, garbage, warfaring, and nuclear weapons wastes. Distortionary policies also contribute; examples are agricultural trade protection, land mismanagement, urban bias in expenditures, and institutional rigidity., Poor nations are responsible for very little pollution because poverty allows little waste or expenditures for polluting, synthetic technologies. The proximal causes of pollution include numbers and rate of growth of populations responsible for the pollution. Since change in the ultimate cause of pollution remains out of reach, altering the numbers of polluters can make a difference. Predictions are made for proportions of the world's total waste production, assuming current 1.6 tons/capita for developed countries and 0.17 tons/capita for developing countries. If developing countries grow at current rates and become more wealthy, they will be emitting half the world's waste by 2025. ON the other hand, unsustainable population growth goes along with inadequate investment in human capital: education, health, employment, infrastructure. The solution is to improve farming technologies in the 117 non-self-sufficient countries, fund development in the most unsustainable enclaves of growing countries, break institutionalized socio-political rigidity in these enclaves, and focus on

  14. Ultimate Drivers and Proximate Correlates of Polyandry in Predatory Mites.

    PubMed

    Schausberger, Peter; Patiño-Ruiz, J David; Osakabe, Masahiro; Murata, Yasumasa; Sugimoto, Naoya; Uesugi, Ryuji; Walzer, Andreas

    2016-01-01

    Polyandry is more widespread than anticipated from Bateman's principle but its ultimate (evolutionary) causes and proximate (mechanistic) correlates are more difficult to pinpoint than those of polygyny. Here, we combined mating experiments, quantification of reproductive traits and microsatellite genotyping to determine the fitness implications of polyandry in two predatory mite species, where males are highly polygynous (up to 45 fertilized females during life), whereas females range from monandry to various polyandry levels. The medium-level polyandrous (up to eight male mates possible) Neoseiulus californicus received clear direct and indirect benefits: multiply mated females produced more offspring with higher survival chances over longer times than singly mated females. In contrast, singly and multiply mated females of the low-level polyandrous (commonly two male mates at maximum) Phytoseiulus persimilis produced similar numbers of offspring having similar survival chances. In both species, multiple mating resulted in mixed offspring paternities, opening the chance for indirect fitness benefits such as enhanced genetic compatibility, complementarity and/or variability. However, the female re-mating likelihood and the paternity chance of non-first male mates were lower in P. persimilis than in N. californicus. Regarding proximate factors, in both species first mating duration and female re-mating likelihood were negatively correlated. Based on occasional fertilization failure of first male mates in P. persimilis, and mixed offspring paternities in both species, we argue that fertilization assurance and the chance to gain indirect fitness benefits are the ultimate drivers of polyandry in P. persimilis, whereas those of N. californicus are higher offspring numbers coupled with enhanced offspring viability and possibly other indirect fitness benefits. Overall, the adaptive significance and proximate events well reflected the polyandry levels. Our study provides a

  15. [The complications of selective proximal vagotomy and their dietetic correction].

    PubMed

    Matveeva, I I

    1990-01-01

    Complications of selective proximal vagotomy (SPV) in patients operated on for duodenal ulcer were considered in relation to the operation type and the time since it has been performed. The syndromes directly related to parasympathetic denervation of the stomach and varying concomitant digestive disorders were revealed in these patients that necessitated administration of adequate diets. All the patients responded well to the dietotherapy. The observations conducted have proved that to prevent the ulcer relapsing, and digestive disorders, and to maintain working capacity, the patients with SPV complications should keep the diet recommended for a long term. PMID:2346006

  16. A simple method of intramedullary fixation for proximal interphalangeal arthrodesis.

    PubMed

    Canales, Michael B; Razzante, Mark C; Ehredt, Duane J; Clougherty, Coleman O

    2014-01-01

    Lesser digital arthrodesis has become one of the most widely used techniques in foot and ankle surgery. When performing digital arthrodesis, surgeons have an abundance of options for implantable devices. We provide information on a simple method of achieving successful arthrodesis. An intramedullary Kirschner wire is implanted into the proximal phalanx with the intermediate phalanx compressed over the wire for rigid internal fixation to avoid the use of an external device. We have had results similar to those from the published data of more expensive implants. PMID:24846156

  17. Cascading failures in networks with proximate dependent nodes.

    PubMed

    Kornbluth, Yosef; Lowinger, Steven; Cwilich, Gabriel; Buldyrev, Sergey V

    2014-03-01

    We study the mutual percolation of a system composed of two interdependent random regular networks. We introduce a notion of distance to explore the effects of the proximity of interdependent nodes on the cascade of failures after an initial attack. We find a nontrivial relation between the nature of the transition through which the networks disintegrate and the parameters of the system, which are the degree of the nodes and the maximum distance between interdependent nodes. We explain this relation by solving the problem analytically for the relevant set of cases. In the process, we solve a variant of Rényi's parking problem on treelike graphs. PMID:24730900

  18. Inversion of ferromagnetic proximity polarization by MgO interlayers.

    PubMed

    Li, Yan; Chye, Y; Chiang, Y F; Pi, K; Wang, W H; Stephens, J M; Mack, S; Awschalom, D D; Kawakami, R K

    2008-06-13

    We investigate the spin-dependent reflection properties in Fe/MgO/GaAs heterostructures by optical pump-probe measurement of the ferromagnetic proximity polarization (FPP). As a function of MgO thickness, the FPP is initially enhanced (<2.0 A) and then exhibits an unexpected sign reversal at approximately 5.0 A. The identification of two competing thresholds in the intensity dependence of FPP and the observation of FPP sign reversal in Fe/Mg/GaAs suggest that the inversion of FPP is related to an interfacial bonding effect. PMID:18643542

  19. Models of proximate and ultimate causation in psychology.

    PubMed

    Alessi, G

    1992-11-01

    B. F. Skinner saw behavior as a product of three levels of evolution. J. R. Kantor and Gregory Bateson noted similar relations. This article describes and applies basic evolutionary concepts to each level: (a) phylogenic, (b) ontogenic, and (c) cultural evolution. Each level is analyzed in terms of (a) units of selection, (b) variety of units required for the selection process, (c) selection pressures, (d) interactions among levels, and (e) implications for understanding and predicting behavior. Distinguishing between models of proximate and ultimate causation, as in biology, may help clarify research problems posed by, and facilitate better communication among, psychologists. PMID:1482003

  20. Radial shortening following a fracture of the proximal radius

    PubMed Central

    2011-01-01

    Background and purpose The Essex-Lopresti lesion is thought to be rare, with a varying degree of disruption to forearm stability probable. We describe the range of radial shortening that occurs following a fracture of the proximal radius, as well as the short-term outcome in these patients. Patients and methods Over an 18-month period, we prospectively assessed all patients with a radiographically confirmed proximal radial fracture. Patients noted to have ipsilateral wrist pain at initial presentation underwent bilateral radiography to determine whether there was disruption of the distal radio-ulnar joint suggestive of an Essex-Lopresti lesion. Outcome was assessed after a mean of 6 (1.5–12) months using clinical and radiographic results, including the Mayo elbow score (MES) and the short musculoskeletal function assessment (SMFA) questionnaire. One patient with a Mason type-I fracture was lost to follow-up after initial presentation. Results 60 patients had ipsilateral wrist pain at the initial assessment of 237 proximal radial fractures. Radial shortening of ≥ 2mm (range: 2–4mm) was seen in 22 patients (mean age 48 (19–79) years, 16 females). The most frequent mechanism of injury was a fall from standing height (10/22). 21 fractures were classified as being Mason type-I or type-II, all of which were managed nonoperatively. One Mason type-III fracture underwent acute radial head replacement. Functional outcome was assessed in 21 patients. We found an excellent or good MES in 18 of the 20 patients with a Mason type-I or type-II injury. Interpretation The incidence of the Essex-Lopresti lesion type is possibly under-reported as there is a spectrum of injuries, and subtle disruptions often go unidentified. A full assessment of all patients with a proximal radial fracture is required in order to identify these injuries, and the index of suspicion is raised as the complexity of the fracture increases. PMID:21504305

  1. Theory of Casimir Forces without the Proximity-Force Approximation.

    PubMed

    Lapas, Luciano C; Pérez-Madrid, Agustín; Rubí, J Miguel

    2016-03-18

    We analyze both the attractive and repulsive Casimir-Lifshitz forces recently reported in experimental investigations. By using a kinetic approach, we obtain the Casimir forces from the power absorbed by the materials. We consider collective material excitations through a set of relaxation times distributed in frequency according to a log-normal function. A generalized expression for these forces for arbitrary values of temperature is obtained. We compare our results with experimental measurements and conclude that the model goes beyond the proximity-force approximation. PMID:27035293

  2. Theory of Casimir Forces without the Proximity-Force Approximation

    NASA Astrophysics Data System (ADS)

    Lapas, Luciano C.; Pérez-Madrid, Agustín; Rubí, J. Miguel

    2016-03-01

    We analyze both the attractive and repulsive Casimir-Lifshitz forces recently reported in experimental investigations. By using a kinetic approach, we obtain the Casimir forces from the power absorbed by the materials. We consider collective material excitations through a set of relaxation times distributed in frequency according to a log-normal function. A generalized expression for these forces for arbitrary values of temperature is obtained. We compare our results with experimental measurements and conclude that the model goes beyond the proximity-force approximation.

  3. STM/STS on proximity-coupled superconducting graphene

    NASA Astrophysics Data System (ADS)

    Ovadia, Maoz; Ji, Yu; Lee, Gil-Ho; Fang, Wenjing; Hoffman, Jennifer; Jarillo-Herrero, Pablo; Kong, Jing; Kim, Philip

    Graphene in good electrical contact with a superconductor has been observed to have an enhanced proximity effect. Application of a magnetic field is expected to generate an Abrikosov lattice of superconducting vortices, each containing Andreev bound states in its core. With our versatile, homebuilt, low temperature scanning tunneling force microscope (STM/SFM), we investigate the electronic properties of graphene on superconducting NbSe2 in a magnetic field and search for signatures of these vortex core states. This work was supported by the STC Center for Integrated Quantum Materials, NSF Grant No. DMR-1231319.

  4. Distributed proximity sensor system having embedded light emitters and detectors

    NASA Technical Reports Server (NTRS)

    Lee, Sukhan (Inventor)

    1990-01-01

    A distributed proximity sensor system is provided with multiple photosensitive devices and light emitters embedded on the surface of a robot hand or other moving member in a geometric pattern. By distributing sensors and emitters capable of detecting distances and angles to points on the surface of an object from known points in the geometric pattern, information is obtained for achieving noncontacting shape and distance perception, i.e., for automatic determination of the object's shape, direction and distance, as well as the orientation of the object relative to the robot hand or other moving member.

  5. Stress fracture of the proximal phalanx of the great toe.

    PubMed

    Shiraishi, M; Mizuta, H; Kubota, K; Sakuma, K; Takagi, K

    1993-01-01

    Three cases of stress fracture of the proximal phalanx of the great toe occurring in a 12-year-old female volleyball player, a 17-year-old female long distance runner, and a 12-year-old male soccer player are reported. This condition probably develops after repeated forced dorsiflexion of the first metatarsophalangeal joint with changing steps. When athletes who repeatedly run and jump complain of pain in the first metatarsophalangeal joint, and there is no history of trauma, this condition should also be considered. PMID:8425728

  6. Endoluminal vacuum therapy for iatrogenic perforation of the proximal oesophagus.

    PubMed

    Möschler, O; Müller, M K

    2014-03-01

    Iatrogenic perforation of the upper gastrointestinal tract is one of the most serious complications of upper gastrointestinal endoscopy, with high rates of morbidity and mortality. Treatment is challenging because stent placement or surgical repair of the perforation in this area is often impossible. We report on two cases of iatrogenic perforations of the very proximal oesophagus and distal hypopharynx which could be successfully closed by using an endoluminal vacuum sponge treatment for 5 days. Thus, the endoluminal vacuum therapy may be a useful alternative to surgery in such cases of difficultly managable perforations of the upper oesophagus. PMID:24622870

  7. Proximal Humerus Fracture Plating Through the Extended Anterolateral Approach.

    PubMed

    Gardner, Michael J

    2016-08-01

    Several approaches to the proximal humerus for fracture fixation are possible. The traditional utilitarian approach to the shoulder, the deltopectoral, has distinct disadvantages when performing fracture reduction and locked plating. The anterolateral acromial approach exploits the intermuscular plane between the anterior and middle heads of the deltoid. After identifying the position of the axillary nerve as it crosses this interval, fracture reduction and fixation is performed. Direct access to both the greater and the lesser tuberosities is facilitated. The cancellous surface of the humeral head fragment provides an excellent surface for direct manipulation without further endangering the extraosseous soft tissue attachments. PMID:27441923

  8. Electrodiagnosis of brachial plexopathies and proximal upper extremity neuropathies.

    PubMed

    Simmons, Zachary

    2013-02-01

    This article describes the normal anatomy of the brachial plexus and its major terminal branches, as well as the major causes and clinical presentations of lesions of these structures. An approach to electrodiagnosis of brachial plexopathies and proximal upper extremity neuropathies is provided, with an emphasis on those nerve conduction studies and portions of the needle examination, which permit localization of lesions to specific trunks, cords, and terminal branches. The importance of specific sensory nerve conduction studies for differentiating plexopathies from radiculopathies and mononeuropathies is emphasized. PMID:23177028

  9. The Proximal Trajectory Algorithm in SVM Cross Validation.

    PubMed

    Astorino, Annabella; Fuduli, Antonio

    2016-05-01

    We propose a bilevel cross-validation scheme for support vector machine (SVM) model selection based on the construction of the entire regularization path. Since such path is a particular case of the more general proximal trajectory concept from nonsmooth optimization, we propose for its construction an algorithm based on solving a finite number of structured linear programs. Our methodology, differently from other approaches, works directly on the primal form of SVM. Numerical results are presented on binary data sets drawn from literature. PMID:27101080

  10. Ground plane insulating coating for proximity focused devices

    DOEpatents

    Power, G.D.

    1998-07-14

    A thin layer of alumina (aluminum oxide) is coated onto the ground plane of a microchannel plate (MCP) without covering the pores of the MCP so it does not effect the performance. The coating is sputtered onto the ground plane at a very steep angle. The addition of the thin dielectric coating of alumina greatly improves the spatial resolution of proximity focused image intensifiers using a narrow gap between the phosphor screen and the MCP. With the coating on the ground plane and the same gap the phosphor screen can be ran at 9000 volts, as compared to 3 kV without the coating. 3 figs.

  11. Ground plane insulating coating for proximity focused devices

    DOEpatents

    Power, Gary D.

    1998-01-01

    A thin layer of alumina (aluminum oxide) is coated onto the ground plane of a microchannel plate (MCP) without covering the pores of the MCP so it does not effect the performance. The coating is sputtered onto the ground plane at a very steep angle. The addition of the thin dielectric coating of alumina greatly improves the spatial resolution of proximity focused image intensifiers using a narrow gap between the phosphor screen and the MCP. With the coating on the ground plane and the same gap the phosphor screen can be ran at 9000 volts, as compared to 3 kV without the coating.

  12. Retained Urethral Catheter Secondary to Placement in Proximal Ureter

    PubMed Central

    Sharda, Rajan

    2016-01-01

    We present an unusual complication secondary to indwelling urethral catheter placement. Routine catheter placement by the obstetrics team in a postpartum female leads to retention of the catheter and inability of its removal by both the obstetrics and urology teams. Although a retained urinary catheter is relatively common, inability to remove a catheter secondary to placement inadvertently into a ureter is extremely rare. In this paper we will discuss the options in removing a retained catheter and present our case of a retained catheter secondary to placement within the right proximal ureter. PMID:27144050

  13. A General Simulation Method for Multiple Bodies in Proximate Flight

    NASA Technical Reports Server (NTRS)

    Meakin, Robert L.

    2003-01-01

    Methods of unsteady aerodynamic simulation for an arbitrary number of independent bodies flying in close proximity are considered. A novel method to efficiently detect collision contact points is described. A method to compute body trajectories in response to aerodynamic loads, applied loads, and inter-body collisions is also given. The physical correctness of the methods are verified by comparison to a set of analytic solutions. The methods, combined with a Navier-Stokes solver, are used to demonstrate the possibility of predicting the unsteady aerodynamics and flight trajectories of moving bodies that involve rigid-body collisions.

  14. Proximity effect thermometer for local temperature measurements on mesoscopic samples.

    SciTech Connect

    Aumentado, J.; Eom, J.; Chandrasekhar, V.; Baldo, P. M.; Rehn, L. E.; Materials Science Division; Northwestern Univ; Univ. of Chicago

    1999-11-29

    Using the strong temperature-dependent resistance of a normal metal wire in proximity to a superconductor, we have been able to measure the local temperature of electrons heated by flowing a direct-current (dc) in a metallic wire to within a few tens of millikelvin at low temperatures. By placing two such thermometers at different parts of a sample, we have been able to measure the temperature difference induced by a dc flowing in the samples. This technique may provide a flexible means of making quantitative thermal and thermoelectric measurements on mesoscopic metallic samples.

  15. Acute tumor lysis syndrome after proximal splenic artery embolization.

    PubMed

    Salsamendi, Jason T; Doshi, Mehul H; Gortes, Francisco J; Levi, Joe U; Narayanan, Govindarajan

    2016-06-01

    Preoperative splenic artery embolization for massive splenomegaly has been shown to reduce intraoperative hemorrhage during splenectomy. We describe a case of tumor lysis syndrome after proximal splenic artery embolization in a patient with advanced mantle cell lymphoma and splenic involvement. The patient presented initially with hyperkalemia two days after embolization that worsened during splenectomy. He was stabilized, but developed laboratory tumor lysis syndrome with renal failure and expired. High clinical suspicion of tumor lysis syndrome in this setting is advised. Treatment must be started early to avoid serious renal injury and death. Lastly, same day splenectomy and embolization should be considered to decrease the likelihood of developing tumor lysis syndrome. PMID:27257458

  16. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

    PubMed Central

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718

  17. Using image processing techniques on proximity probe signals in rotordynamics

    NASA Astrophysics Data System (ADS)

    Diamond, Dawie; Heyns, Stephan; Oberholster, Abrie

    2016-06-01

    This paper proposes a new approach to process proximity probe signals in rotordynamic applications. It is argued that the signal be interpreted as a one dimensional image. Existing image processing techniques can then be used to gain information about the object being measured. Some results from one application is presented. Rotor blade tip deflections can be calculated through localizing phase information in this one dimensional image. It is experimentally shown that the newly proposed method performs more accurately than standard techniques, especially where the sampling rate of the data acquisition system is inadequate by conventional standards.

  18. Pulse compression grating fabrication by diffractive proximity photolithography.

    PubMed

    Stuerzebecher, Lorenz; Fuchs, Frank; Harzendorf, Torsten; Zeitner, Uwe D

    2014-02-15

    We report about a newly devised throughput-scalable fabrication method for high-quality periodic submicron structures. The process is demonstrated for optical transmission gratings in fused silica with a period of 800 nm (1250  lines/mm) to be used in laser pulse compression. The technology is based on an innovative advancement of i-line proximity photolithography performed in a mask aligner. The aerial image is encoded in a rigorously optimized electron-beam-written three-level phase mask which is illuminated by an adapted multipole configuration of incidence angles. In comparison to conventional proximity lithography, the process enables a significantly higher resolution while maintaining a good depth of focus--in contrast to lithography based on direct Talbot-imaging. Details about the grating fabrication process and characterization of fabricated pulse compression grating wafers are presented. The gratings show a diffraction efficiency of 97% at a wavelength of 1030 nm and a wavefront error comparable to gratings fabricated by electron-beam lithography. PMID:24562273

  19. A method for sex estimation using the proximal femur.

    PubMed

    Curate, Francisco; Coelho, João; Gonçalves, David; Coelho, Catarina; Ferreira, Maria Teresa; Navega, David; Cunha, Eugénia

    2016-09-01

    The assessment of sex is crucial to the establishment of a biological profile of an unidentified skeletal individual. The best methods currently available for the sexual diagnosis of human skeletal remains generally rely on the presence of well-preserved pelvic bones, which is not always the case. Postcranial elements, including the femur, have been used to accurately estimate sex in skeletal remains from forensic and bioarcheological settings. In this study, we present an approach to estimate sex using two measurements (femoral neck width [FNW] and femoral neck axis length [FNAL]) of the proximal femur. FNW and FNAL were obtained in a training sample (114 females and 138 males) from the Luís Lopes Collection (National History Museum of Lisbon). Logistic regression and the C4.5 algorithm were used to develop models to predict sex in unknown individuals. Proposed cross-validated models correctly predicted sex in 82.5-85.7% of the cases. The models were also evaluated in a test sample (96 females and 96 males) from the Coimbra Identified Skeletal Collection (University of Coimbra), resulting in a sex allocation accuracy of 80.1-86.2%. This study supports the relative value of the proximal femur to estimate sex in skeletal remains, especially when other exceedingly dimorphic skeletal elements are not accessible for analysis. PMID:27373600

  20. Cassini at Saturn Proximal Orbits - Attitude Control Challenges

    NASA Technical Reports Server (NTRS)

    Burk, Thomas A.

    2013-01-01

    The Cassini mission at Saturn will come to an end in the spring and summer of 2017 with a series of 22 orbits that will dip inside the rings of Saturn. These are called proximal orbits and will conclude with spacecraft disposal into the atmosphere of the ringed world on September 15, 2017. These unique orbits that cross the ring plane only a few thousand kilometers above the cloud tops of the planet present new attitude control challenges for the Cassini operations team. Crossing the ring plane so close to the inner edge of the rings means that the Cassini orientation during the crossing will be tailored to protect the sensitive electronics bus of the spacecraft. This orientation will put the sun sensors at some extra risk so this paper discusses how the team prepares for dust hazards. Periapsis is so close to the planet that spacecraft controllability with RCS thrusters needs to be evaluated because of the predicted atmospheric torque near closest approach to Saturn. Radiation during the ring plane crossings will likely trigger single event transients in some attitude control sensors. This paper discusses how the attitude control team deals with radiation hazards. The angular size and unique geometry of the rings and Saturn near periapsis means that star identification will be interrupted and this paper discusses how the safe mode attitude is selected to best deal with these large bright bodies during the proximal orbits.

  1. Method to measure tone of axial and proximal muscle.

    PubMed

    Gurfinkel, Victor S; Cacciatore, Timothy W; Cordo, Paul J; Horak, Fay B

    2011-01-01

    The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974

  2. New Advances in the Study of the Proximal Point Algorithm

    NASA Astrophysics Data System (ADS)

    Moroşanu, Gheorghe

    2010-09-01

    Consider in a real Hilbert space H the inexact, Halpern-type, proximal point algorithm xn+1 = αnu+(1-αn)Jβnxn+en, n = 0,1,…, (H—PPA) where u, x∈H are given points, Jβn = (I+βna) for a given maximal monotone operator A, and (en) is the error sequence, under new assumptions on αn∈(0,1) and βn∈(0,1). Several strong convergence results for the H—PPA are presented under the general condition that the error sequence converges strongly to zero, thus improving the classical Rockafellar's summability condition on (‖en‖) that has been extensively used so far for different versions of the proximal point algorithm. Our results extend and improve some recent ones. These results can be applied to approximate minimizers of convex functionals. Convergence rate estimates are established for a sequence approximating the minimum value of such a functional.

  3. Rotor Vortex Wake in Close Proximity of Walls in Hover

    NASA Astrophysics Data System (ADS)

    Konus, Mehmet Fatih; Savas, Omer

    2014-11-01

    Expanding flight envelopes of rotorcraft raise concerns about their behavior in very close proximity of walls or corners where the separation between the wall and the rotor disk can almost vanish. A series of experiments are conducted in a water tank to study the hover behavior of the wake of a 25-cm diameter three-bladed rotor at 8 rev/s. Particle image velocimetry, strain gage force balance measurements and flow visualization are employed. The vortex wake, which is axisymmetric on the average in an unbounded surrounding, is distorted increasingly with decreasing separation from a wall or corner. The vortex wake bends toward the wall and into the corner. The individual helical filaments off the rotor tips are distorted and closely follow the wall. Intermittent reversed vortical flow regions appear upstream of the rotor disk in the proximity of the wall. The mean streamlines indicate that the wake is bent toward the wall or into the corner. The component of the thrust vector along the axis of the rotor decreases. These observation suggest that the thrust vector progressively deviates from the geometric axis of the rotor.

  4. Stress analyses of joint arthroplasty in the proximal humerus.

    PubMed

    Orr, T E; Carter, D R

    1985-01-01

    Finite element stress analyses were performed on the proximal humerus before and after the simulated implantation of stemmed, metallic prosthetic components with porous sintered surfaces for direct bony attachment. Design geometries with surfaces at the prosthetic head/bone interface that were (a) convex, (b) flat, and (c) concave were studied. Analyses for each of the three geometries were conducted to reflect (a) bone ingrowth on all the prosthesis/bone surfaces and (b) bone ingrowth only along the underside of the prosthetic humeral head (assuming the stem was not coated with a porous material). Three loading conditions were used to model various degrees of abduction of the arm. Results indicated that in the normal humerus the compressive joint forces are transmitted from the articular surface through cancellous bone to the inferior cortical shell. Contraction of the rotator cuff muscles created tensile stresses in the superolateral cancellous bone and the superior cortical shell of the humerus. Results of the implanted humeral component models indicated that the use of a prosthesis with bone ingrowth along the stem would cause marked stress shielding proximally whereas the use of implants with porous ingrowth only on the underside of the humeral head replacement produced stress fields more similar to the normal humerus. The convex, flat, and concave surfaces provided similar load transfer from the component to the underlying bone in all loading cases. Other prosthetic head designs that may offer better initial stability produced stress fields similar to those of existing prostheses. PMID:4032107

  5. Restoring proximal caries lesions conservatively with tunnel restorations

    PubMed Central

    Chu, Chun-Hung; Mei, May L; Cheung, Chloe; Nalliah, Romesh P

    2013-01-01

    The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED) and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations. PMID:24019754

  6. Group Problem Solving as a Zone of Proximal Development activity

    NASA Astrophysics Data System (ADS)

    Brewe, Eric

    2006-12-01

    Vygotsky described learning as a process, intertwined with development, which is strongly influenced by social interactions with others that are at differing developmental stages.i These interactions create a Zone of Proximal Development for each member of the interaction. Vygotsky’s notion of social constructivism is not only a theory of learning, but also of development. While teaching introductory physics in an interactive format, I have found manifestations of Vygotsky’s theory in my classroom. The source of evidence is a paired problem solution. A standard mechanics problem was solved by students in two classes as a homework assignment. Students handed in the homework and then solved the same problem in small groups. The solutions to both the group and individual problem were assessed by multiple reviewers. In many cases the group score was the same as the highest individual score in the group, but in some cases, the group score was higher than any individual score. For this poster, I will analyze the individual and group scores and focus on three groups solutions and video that provide evidence of learning through membership in a Zone of Proximal Development. Endnotes i L. Vygotsky -Mind and society: The development of higher mental processes. Cambridge, MA: Harvard University Press. (1978).

  7. Acid-base transport by the renal proximal tubule

    PubMed Central

    Skelton, Lara A.; Boron, Walter F.; Zhou, Yuehan

    2015-01-01

    Each day, the kidneys filter 180 L of blood plasma, equating to some 4,300 mmol of the major blood buffer, bicarbonate (HCO3−). The glomerular filtrate enters the lumen of the proximal tubule (PT), and the majority of filtered HCO3− is reclaimed along the early (S1) and convoluted (S2) portions of the PT in a manner coupled to the secretion of H+ into the lumen. The PT also uses the secreted H+ to titrate non-HCO3− buffers in the lumen, in the process creating “new HCO3−” for transport into the blood. Thus, the PT – along with more distal renal segments – is largely responsible for regulating plasma [HCO3−]. In this review we first focus on the milestone discoveries over the past 50+ years that define the mechanism and regulation of acid-base transport by the proximal tubule. Further on in the review, we will summarize research still in progress from our laboratory, work that addresses the problem of how the PT is able to finely adapt to acid–base disturbances by rapidly sensing changes in basolateral levels of HCO3− and CO2 (but not pH), and thereby to exert tight control over the acid–base composition of the blood plasma. PMID:21170887

  8. Intramedullary screw fixation of proximal fifth metatarsal fractures in athletes

    PubMed Central

    Massada, Marta Maria Teixeira de Oliveira; Pereira, Manuel Alexandre Negrais Pinho Gonçalves; de Sousa, Ricardo Jorge Gomes; Costa, Paulo Guimarães; Massada, José Leandro da Rocha

    2012-01-01

    Objective The purpose of this study was to review the short- and long-term clinical and radiological results of intramedullary compression screw fixation of proximal fifth metatarsal fractures in athletes. Methods Eleven male and six female active patients with fifth metatarsal zone II and zone III fractures fixed with a 4.5-mm cannulated compression screw were evaluated by chart review, review of radiographs, and clinical evaluation. Fifteen of the patients were high-level athletes (soccer: n=11; basketball: n=1; track and field: n=3) and two were recreational-level athletes. Mean follow-up from surgery to evaluation was 54 (38-70) months. Results Mean time to healing as shown on radiographs and mean time to return to full activity after surgery were 7.3 and 7.5 weeks, respectively. All patients were able to return to their previous levels of activity. There were no reports of union delay, nonunion or refracture to date. Conclusion In our patients, cannulated screw fixation of proximal fifth metatarsal fractures was a reliable procedure with low morbidity associated that provided athletes a quick return to activity. Level of Evidence I, Case Series. PMID:24453614

  9. Proximity to pollution sources and risk of amphibian limb malformation.

    PubMed

    Taylor, Brynn; Skelly, David; Demarchis, Livia K; Slade, Martin D; Galusha, Deron; Rabinowitz, Peter M

    2005-11-01

    The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42-3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem. PMID:16263502

  10. Multisensory simultaneity judgment and proximity to the body.

    PubMed

    Noel, Jean-Paul; Lukowska, Marta; Wallace, Mark; Serino, Andrea

    2016-01-01

    The integration of information across different sensory modalities is known to be dependent upon the statistical characteristics of the stimuli to be combined. For example, the spatial and temporal proximity of stimuli are important determinants with stimuli that are close in space and time being more likely to be bound. These multisensory interactions occur not only for singular points in space/time, but over "windows" of space and time that likely relate to the ecological statistics of real-world stimuli. Relatedly, human psychophysical work has demonstrated that individuals are highly prone to judge multisensory stimuli as co-occurring over a wide range of time--a so-called simultaneity window (SW). Similarly, there exists a spatial representation of peripersonal space (PPS) surrounding the body in which stimuli related to the body and to external events occurring near the body are highly likely to be jointly processed. In the current study, we sought to examine the interaction between these temporal and spatial dimensions of multisensory representation by measuring the SW for audiovisual stimuli through proximal-distal space (i.e., PPS and extrapersonal space). Results demonstrate that the audiovisual SWs within PPS are larger than outside PPS. In addition, we suggest that this effect is likely due to an automatic and additional computation of these multisensory events in a body-centered reference frame. We discuss the current findings in terms of the spatiotemporal constraints of multisensory interactions and the implication of distinct reference frames on this process. PMID:26891828

  11. Modulation of hydrophobic interactions by proximally immobilized ions.

    PubMed

    Ma, C Derek; Wang, Chenxuan; Acevedo-Vélez, Claribel; Gellman, Samuel H; Abbott, Nicholas L

    2015-01-15

    The structure of water near non-polar molecular fragments or surfaces mediates the hydrophobic interactions that underlie a broad range of interfacial, colloidal and biophysical phenomena. Substantial progress over the past decade has improved our understanding of hydrophobic interactions in simple model systems, but most biologically and technologically relevant structures contain non-polar domains in close proximity to polar and charged functional groups. Theories and simulations exploring such nanometre-scale chemical heterogeneity find it can have an important effect, but the influence of this heterogeneity on hydrophobic interactions has not been tested experimentally. Here we report chemical force microscopy measurements on alkyl-functionalized surfaces that reveal a dramatic change in the surfaces' hydrophobic interaction strengths on co-immobilization of amine or guanidine groups. Protonation of amine groups doubles the strength of hydrophobic interactions, and guanidinium groups eliminate measurable hydrophobic interactions in all pH ranges investigated. We see these divergent effects of proximally immobilized cations also in single-molecule measurements on conformationally stable β-peptides with non-polar subunits located one nanometre from either amine- or guanidine-bearing subunits. Our results demonstrate the importance of nanometre-scale chemical heterogeneity, with hydrophobicity not an intrinsic property of any given non-polar domain but strongly modulated by functional groups located as far away as one nanometre. The judicious placing of charged groups near hydrophobic domains thus provides a strategy for tuning hydrophobic driving forces to optimize molecular recognition or self-assembly processes. PMID:25592540

  12. Posteromedial approach to proximal tibia for corticotomy in callus distractions.

    PubMed

    Heiss, C; Meissner, S A; Hoesel, L M; Pfeil, J; Schnettler, R

    2006-10-01

    Corticotomy of the tibia using Ilizarov's anterolateral approach is used routinely for callus distraction. This method is associated with impaired callus formation and delayed healing because of marginal soft tissue covering and blood supply to the proximal tibia. We presumed a newly designed posteromedial approach would result in less callus defects and improved healing. In this prospective, randomized study, 31 patients had callus distraction using an anterolateral approach or the newly designed posteromedial approach. Callus formation was assessed radiographically and histologically. Callus defects were classified using serial radiographs. Biopsy specimens were taken from high-grade defect (Grades 3-4) zones to examine the osteogenic potential. Radiographic evaluation showed 13 callus defects; 12 occurred after the anterolateral approach and only one occurred after the posteromedial method. Although low-grade defects (Grades 1-2) healed spontaneously, biopsy specimens taken from Grades 3-4 defects revealed no osteogenic potential and requiring operative revision. Because of low soft tissue covering and impaired blood supply to the anterior tibia during surgical exposure for corticotomy, less callus formation occurred after the anterolateral approach compared with the posteromedial approach. We recommend the less invasive posteromedial approach to reduce callus defects and impaired healing in callus distraction of the proximal tibia. PMID:16760808

  13. Cancer risk and residential proximity to cranberry cultivation in Massachusetts.

    PubMed Central

    Aschengrau, A; Ozonoff, D; Coogan, P; Vezina, R; Heeren, T; Zhang, Y

    1996-01-01

    OBJECTIVES: This study evaluated the relationship between cancer risk and residential proximity to cranberry cultivation. METHODS: A population-based case-control study was conducted. Cases, diagnosed during 1983 through 1986 among residents of the Upper Cape Cod area of Massachusetts, involved incident cancers of the lung (n = 252), breast (n = 265), colon-rectum (n = 326), bladder (n = 63), kidney (n = 35), pancreas (n = 37), and brain (n = 37), along with leukemia (n = 35). Control subjects were randomly selected from among telephone subscribers (n = 184), Medicare beneficiaries (n = 464), and deceased individuals (n = 723). RESULTS: No meaningful increases in risk were seen for any of the cancer sites except for the brain. When latency was considered, subjects who had ever lived within 2600 ft (780 m) of a cranberry bog had a twofold increased risk of brain cancer overall (95% confidence interval [CI] = 0.8, 4.9) and a 6.7-fold increased risk of astrocytoma (95% CI = 1.6, 27.8). CONCLUSIONS: Residential proximity to cranberry bog cultivation was not associated with seven of the eight cancers investigated; however, an association was observed with brain cancer, particularly astrocytoma. Larger, more detailed studies are necessary to elucidate this relationship. PMID:8806382

  14. Preparation of the proximal femur in cementless total hip revision.

    PubMed

    Mallory, T H

    1988-10-01

    With an increased incidence of revision for the failed cemented total hip arthroplasty, techniques of revision surgery need meticulous attention to detail. Although the causes of the failed cemented total hip arthroplasty are many, they tend to follow characteristic patterns. The proximal femur can be exposed through an extensive muscle split incision, which offers a complete circumferential view of the femur. The cement removal is enhanced by controlled perforation using high-speed drills. Classification of bony deficits of the proximal femur can be divided into Type I, including intact cortex and medullary content; Type II, in which there is intact cortex but deficient medullary content; and Type III, in which deficits of both the cortex and medullary canal are present. Prosthetic selection is based on residual bone stock. In general, cementless fixation is advocated, with distal fixation using long-stem devices. Augmentation of bone deficits requires the use of segmental prosthetic replacement or fresh-frozen allografts. One hundred sixty patients were followed for two to six years. Satisfactory results have occurred in over 90% of the patients; better results are anticipated in patients with minimal bone deficits. Aseptic loosening requiring rerevision has occurred in 5% of the patient population. Understanding the dynamics of failure and the residual bone deficits allows one to manage the failed cemented total hip arthroplasty with greater efficiency and predictability. PMID:3416541

  15. Modulation of hydrophobic interactions by proximally immobilized ions

    NASA Astrophysics Data System (ADS)

    Ma, C. Derek; Wang, Chenxuan; Acevedo-Vélez, Claribel; Gellman, Samuel H.; Abbott, Nicholas L.

    2015-01-01

    The structure of water near non-polar molecular fragments or surfaces mediates the hydrophobic interactions that underlie a broad range of interfacial, colloidal and biophysical phenomena. Substantial progress over the past decade has improved our understanding of hydrophobic interactions in simple model systems, but most biologically and technologically relevant structures contain non-polar domains in close proximity to polar and charged functional groups. Theories and simulations exploring such nanometre-scale chemical heterogeneity find it can have an important effect, but the influence of this heterogeneity on hydrophobic interactions has not been tested experimentally. Here we report chemical force microscopy measurements on alkyl-functionalized surfaces that reveal a dramatic change in the surfaces' hydrophobic interaction strengths on co-immobilization of amine or guanidine groups. Protonation of amine groups doubles the strength of hydrophobic interactions, and guanidinium groups eliminate measurable hydrophobic interactions in all pH ranges investigated. We see these divergent effects of proximally immobilized cations also in single-molecule measurements on conformationally stable β-peptides with non-polar subunits located one nanometre from either amine- or guanidine-bearing subunits. Our results demonstrate the importance of nanometre-scale chemical heterogeneity, with hydrophobicity not an intrinsic property of any given non-polar domain but strongly modulated by functional groups located as far away as one nanometre. The judicious placing of charged groups near hydrophobic domains thus provides a strategy for tuning hydrophobic driving forces to optimize molecular recognition or self-assembly processes.

  16. Scintillation proximity assay (SPA) technology to study biomolecular interactions.

    PubMed

    Cook, Neil; Harris, Alison; Hopkins, Alison; Hughes, Kelvin

    2002-05-01

    Scintillation proximity assay (SPA) is a versatile homogeneous technique for radioactive assays which eliminates the need for separation steps. In SPA, scintillant is incorporated into small fluomicrospheres. These microspheres or "beads" are constructed in such a way as to bind specific molecules. If a radioactive molecule is bound to the bead, it is brought into close enough proximity that it can stimulate the scintillant contained within to emit light. Otherwise, the unbound radioactivity is too distant, the energy released is dissipated before reaching the bead, and these disintegrations are not detected. In this unit, the application of SPA technology to measuring protein-protein interactions, Src Homology 2 (SH2) and 3 (SH3) domain binding to specific peptide sequences, and receptor-ligand interactions are described. Three other protocols discuss the application of SPA technology to cell-adhesion-molecule interactions, protein-DNA interactions, and radioimmunoassays. In addition, protocols are given for preparation of SK-N-MC cells and cell membranes. PMID:18429228

  17. Parkinson's Disease Prevalence and Proximity to Agricultural Cultivated Fields

    PubMed Central

    Yitshak Sade, Maayan; Zlotnik, Yair; Kloog, Itai; Novack, Victor; Peretz, Chava; Ifergane, Gal

    2015-01-01

    The risk for developing Parkinson's disease (PD) is a combination of multiple environmental and genetic factors. The Negev (Southern Israel) contains approximately 252.5 km2 of agricultural cultivated fields (ACF). We aimed to estimate the prevalence and incidence of PD and to examine possible geographical clustering and associations with agricultural exposures. We screened all “Clalit” Health Services members in the Negev (70% of the population) between the years 2000 and 2012. Individual demographic, clinical, and medication prescription data were available. We used a refined medication tracer algorithm to identify PD patients. We used mixed Poisson models to calculate the smoothed standardized incidence rates (SIRs) for each locality. We identified ACF and calculate the size and distance of the fields from each locality. We identified 3,792 cases of PD. SIRs were higher than expected in Jewish rural localities (median SIR [95% CI]: 1.41 [1.28; 1.53] in 2001–2004, 1.62 [1.48; 1.76] in 2005–2008, and 1.57 [1.44; 1.80] in 2009–2012). Highest SIR was observed in localities located in proximity to large ACF (SIR 1.54, 95% CI 1.32; 1.79). In conclusion, in this population based study we found that PD SIRs were higher than expected in rural localities. Furthermore, it appears that proximity to ACF and the field size contribute to PD risk. PMID:26357584

  18. Uncertainty quantification for personalized analyses of human proximal femurs.

    PubMed

    Wille, Hagen; Ruess, Martin; Rank, Ernst; Yosibash, Zohar

    2016-02-29

    Computational models for the personalized analysis of human femurs contain uncertainties in bone material properties and loads, which affect the simulation results. To quantify the influence we developed a probabilistic framework based on polynomial chaos (PC) that propagates stochastic input variables through any computational model. We considered a stochastic E-ρ relationship and a stochastic hip contact force, representing realistic variability of experimental data. Their influence on the prediction of principal strains (ϵ1 and ϵ3) was quantified for one human proximal femur, including sensitivity and reliability analysis. Large variabilities in the principal strain predictions were found in the cortical shell of the femoral neck, with coefficients of variation of ≈40%. Between 60 and 80% of the variance in ϵ1 and ϵ3 are attributable to the uncertainty in the E-ρ relationship, while ≈10% are caused by the load magnitude and 5-30% by the load direction. Principal strain directions were unaffected by material and loading uncertainties. The antero-superior and medial inferior sides of the neck exhibited the largest probabilities for tensile and compression failure, however all were very small (pf<0.001). In summary, uncertainty quantification with PC has been demonstrated to efficiently and accurately describe the influence of very different stochastic inputs, which increases the credibility and explanatory power of personalized analyses of human proximal femurs. PMID:26873282

  19. High-accuracy simulation-based optical proximity correction

    NASA Astrophysics Data System (ADS)

    Keck, Martin C.; Henkel, Thomas; Ziebold, Ralf; Crell, Christian; Thiele, J.÷rg

    2003-12-01

    In times of continuing aggressive shrinking of chip layouts a thorough understanding of the pattern transfer process from layout to silicon is indispensable. We analyzed the most prominent effects limiting the control of this process for a contact layer like process, printing 140nm features of variable length and different proximity using 248nm lithography. Deviations of the photo mask from the ideal layout, in particular mask off-target and corner rounding have been identified as clearly contributing to the printing behavior. In the next step, these deviations from ideal behavior have been incorporated into the optical proximity correction (OPC) modeling process. The degree of accuracy for describing experimental data by simulation, using an OPC model modified in that manner could be increased significantly. Further improvement in modeling the optical imaging process could be accomplished by taking into account lens aberrations of the exposure tool. This suggests a high potential to improve OPC by considering the effects mentioned, delivering a significant contribution to extending the application of OPC techniques beyond current limits.

  20. Measurements of the dc Josephson current in proximity systems

    SciTech Connect

    Camerlingo, C.; Monaco, R.; Ruggiero, B.; Russo, M. ); Testa, G. )

    1995-03-01

    Junctions modeled as [ital S]-[ital N]/[ital I]/[ital S] and [ital S]-[ital N]/[ital I]/[ital N]-[ital S] proximity systems (where [ital S], [ital I], and [ital N] indicate a superconductor, an insulator, and a normal metal, respectively) are widely discussed in literature from both the experimental and theoretical point of view. In the present paper experimental aspects concerning Nb/Nb junctions including a proximity bilayer are considered. Nb-[ital M]/[ital I]/Nb and [ital M]-Nb/[ital I]/Nb structures (where [ital M] is a normal metal, a semimetal, or a superconductor) are investigated by using a semimetal (bismuth) and a superconductor (aluminum) as the [ital M] layer. In particular, how the deposition of a back layer influences the behavior of Nb/[ital I]/Nb high-quality junctions is discussed, focusing the interest on measurements of the temperature dependence of the maximum dc Josephson current. Experimental data are discussed in the framework of Kresin's theoretical calculations based on the thermodynamic Green's function method.

  1. Cell osmotic water permeability of isolated rabbit proximal convoluted tubules.

    PubMed

    Carpi-Medina, P; González, E; Whittembury, G

    1983-05-01

    Cell osmotic water permeability, Pcos, of the peritubular aspect of the proximal convoluted tubule (PCT) was measured from the time course of cell volume changes subsequent to the sudden imposition of an osmotic gradient, delta Cio, across the cell membrane of PCT that had been dissected and mounted in a chamber. The possibilities of artifact were minimized. The bath was vigorously stirred, the solutions could be 95% changed within 0.1 s, and small osmotic gradients (10-20 mosM) were used. Thus, the osmotically induced water flow was a linear function of delta Cio and the effect of the 70-microns-thick unstirred layers was negligible. In addition, data were extrapolated to delta Cio = 0. Pcos for PCT was 41.6 (+/- 3.5) X 10(-4) cm3 X s-1 X osM-1 per cm2 of peritubular basal area. The standing gradient osmotic theory for transcellular osmosis is incompatible with this value. Published values for Pcos of PST are 25.1 X 10(-4), and for the transepithelial permeability Peos values are 64 X 10(-4) for PCT and 94 X 10(-4) for PST, in the same units. These results indicate that there is room for paracellular water flow in both nephron segments and that the magnitude of the transcellular and paracellular water flows may vary from one segment of the proximal tubule to another. PMID:6846543

  2. Vision-based proximity detection in retinal surgery.

    PubMed

    Richa, R; Balicki, M; Sznitman, R; Meisner, E; Taylor, R; Hager, G

    2012-08-01

    In retinal surgery, surgeons face difficulties such as indirect visualization of surgical targets, physiological tremor, and lack of tactile feedback, which increase the risk of retinal damage caused by incorrect surgical gestures. In this context, intraocular proximity sensing has the potential to overcome current technical limitations and increase surgical safety. In this paper, we present a system for detecting unintentional collisions between surgical tools and the retina using the visual feedback provided by the opthalmic stereo microscope. Using stereo images, proximity between surgical tools and the retinal surface can be detected when their relative stereo disparity is small. For this purpose, we developed a system comprised of two modules. The first is a module for tracking the surgical tool position on both stereo images. The second is a disparity tracking module for estimating a stereo disparity map of the retinal surface. Both modules were specially tailored for coping with the challenging visualization conditions in retinal surgery. The potential clinical value of the proposed method is demonstrated by extensive testing using a silicon phantom eye and recorded rabbit in vivo data. PMID:22692869

  3. Orion Handling Qualities During ISS Proximity Operations and Docking

    NASA Technical Reports Server (NTRS)

    Stephens, John-Paul; Vos, Gordon A.; Bilimoria, Karl D.; Mueller, Eric R.; Brazzel, Jack; Spehar, Pete

    2011-01-01

    NASA's Orion spacecraft is designed to autonomously rendezvous and dock with many vehicles including the International Space Station. However, the crew is able to assume manual control of the vehicle s attitude and flight path. In these instances, Orion must meet handling qualities requirements established by NASA. Two handling qualities assessments were conducted at the Johnson Space Center to evaluate preliminary designs of the vehicle using a six degree of freedom, high-fidelity guidance, navigation, and control simulation. The first assessed Orion s handling qualities during the last 20 ft before docking, and included both steady and oscillatory motions of the docking target. The second focused on manual acquisition of the docking axis during the proximity operations phase and subsequent station-keeping. Cooper-Harper handling qualities ratings, workload ratings and comments were provided by 10 evaluation pilots for the docking study and 5 evaluation pilots for the proximity operations study. For the docking task, both cases received 90% Level 1 (satisfactory) handling qualities ratings, exceeding NASA s requirement. All ratings for the ProxOps task were Level 1. These evaluations indicate that Orion is on course to meet NASA's handling quality requirements for ProxOps and docking.

  4. The Carbofix™ "Piccolo Proximal femur nail": A new perspective for treating proximal femur lesion. A technique report.

    PubMed

    Zoccali, Carmine; Soriani, Antonella; Rossi, Barbara; Salducca, Nicola; Biagini, Roberto

    2016-12-01

    Metastases to proximal femur are common and surgery is often suggested to prevent fractures; otherwise it is necessary in cases where this has already occurred. Adjuvant radiotherapy is necessary to reduce the risk of local progression. Nevertheless, the success or failure of radiation therapy treatments depends upon the accuracy in which target identification is correct and dose prescription is fulfilled. Unfortunately, the use of titanium nails consistently limits radiation dose; indeed, the presence of ferromagnetic artifacts interferes with target identification. We present the technique for implant a new carbon fiber nail useful to reduce the ferromagnetic artifacts which allows a better adjuvant radiotherapy. PMID:27436924

  5. The functional subunit of a dimeric transcription activator protein depends on promoter architecture.

    PubMed Central

    Zhou, Y; Pendergrast, P S; Bell, A; Williams, R; Busby, S; Ebright, R H

    1994-01-01

    In Class I CAP-dependent promoters, the DNA site for CAP is located upstream of the DNA site for RNA polymerase. In Class II CAP-dependent promoters, the DNA site for CAP overlaps the DNA site for RNA polymerase, replacing the -35 site. We have used an 'oriented heterodimers' approach to identify the functional subunit of CAP at two Class I promoters having different distances between the DNA sites for CAP and RNA polymerase [CC(-61.5) and CC(-72.5)] and at one Class II promoter [CC(-41.5)]. Our results indicate that transcription activation at Class I promoters, irrespective of the distance between the DNA sites for CAP and RNA polymerase, requires the activating region of the promoter-proximal subunit of CAP. In striking contrast, our results indicate that transcription activation at Class II promoters requires the activating region of the promoter-distal subunit of CAP. Images PMID:7925296

  6. Cloning and partial characterization of the mouse glutamine:fructose-6-phosphate amidotransferase (GFAT) gene promoter.

    PubMed Central

    Sayeski, P P; Wang, D; Su, K; Han, I O; Kudlow, J E

    1997-01-01

    Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the enzyme that is rate limiting in the synthesis of glucosamine and hexosamines. Glucosamine has been proposed to contribute to the glucotoxicity of diabetes. Evidence that the gene encoding GFAT is transcriptionally regulated prompted us to clone and characterize its promoter. The position of the mouse GFAT promoter relative to the translational start site was located by primer extension and found to be 149 bp upstream of the translational start site. A 1.9 kb SacI fragment of the GFAT gene was found to contain the promoter and 88 bp of sequence downstream of the transcriptional start site. This promoter segment could drive expression of a luciferase reporter gene, could confer correct transcriptional initiation to the reporter and could confer the EGF-responsiveness previously observed in the native gene. The mouse GFAT promoter lacks a canonical TATA box and has several GC boxes within a highly GC-rich region. Deletional analysis of the promoter indicated that a proximal element extending to -120 relative to the transcriptional start site could confer reporter expression at a level of 57% of the 1.9 kb construct. Detailed analysis of this proximal region by DNase I footprinting, electrophoretic mobility shift assays and site-directed mutagenesis indicated that Sp1 binds to three elements in this proximal promoter segment and plays a vital role in regulation of transcription from this gene. PMID:9060444

  7. Neurons in the Nucleus Accumbens Promote Selection Bias for Nearer Objects

    PubMed Central

    Morrison, Sara E.

    2014-01-01

    Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level. PMID:25319709

  8. Neurons in the nucleus accumbens promote selection bias for nearer objects.

    PubMed

    Morrison, Sara E; Nicola, Saleem M

    2014-10-15

    Both animals and humans often prefer rewarding options that are nearby over those that are distant, but the neural mechanisms underlying this bias are unclear. Here we present evidence that a proximity signal encoded by neurons in the nucleus accumbens drives proximate reward bias by promoting impulsive approach to nearby reward-associated objects. On a novel decision-making task, rats chose the nearer option even when it resulted in greater effort expenditure and delay to reward; therefore, proximate reward bias was unlikely to be caused by effort or delay discounting. The activity of individual neurons in the nucleus accumbens did not consistently encode the reward or effort associated with specific alternatives, suggesting that it does not participate in weighing the values of options. In contrast, proximity encoding was consistent and did not depend on the subsequent choice, implying that accumbens activity drives approach to the nearest rewarding option regardless of its specific associated reward size or effort level. PMID:25319709

  9. Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain

    PubMed Central

    Bargaje, Rhishikesh; Alam, Mohammad Parwez; Patowary, Ashok; Sarkar, Maharnob; Ali, Tamer; Gupta, Shivani; Garg, Manali; Singh, Meghna; Purkanti, Ramya; Scaria, Vinod; Sivasubbu, Sridhar; Brahmachari, Vani; Pillai, Beena

    2012-01-01

    Nucleosome positioning maps of several organisms have shown that Transcription Start Sites (TSSs) are marked by nucleosome depleted regions flanked by strongly positioned nucleosomes. Using genome-wide nucleosome maps and histone variant occupancy in the mouse liver, we show that the majority of genes were associated with a single prominent H2A.Z containing nucleosome in their promoter region. We classified genes into clusters depending on the proximity of H2A.Z to the TSS. The genes with no detectable H2A.Z showed lowest expression level, whereas H2A.Z was positioned closer to the TSS of genes with higher expression levels. We confirmed this relation between the proximity of H2A.Z and expression level in the brain. The proximity of histone variant H2A.Z, but not H3.3 to the TSS, over seven consecutive nucleosomes, was correlated with expression. Further, a nucleosome was positioned over the TSS of silenced genes while it was displaced to expose the TSS in highly expressed genes. Our results suggest that gene expression levels in vivo are determined by accessibility of the TSS and proximity of H2A.Z. PMID:22821566

  10. Pragmatic RCT on the Efficacy of Proximal Caries Infiltration.

    PubMed

    Meyer-Lueckel, H; Balbach, A; Schikowsky, C; Bitter, K; Paris, S

    2016-05-01

    Proximal caries infiltration has been shown to be efficacious in hampering caries lesion progression when performed by dentists working in a university setting. The aim of this randomized split-mouth, placebo-controlled clinical trial was to assess the efficacy of resin infiltration of proximal caries lesions being performed by several dentists in private practices, in combination with individualized oral hygiene plus noninvasive measures compared with these alone. In this study, 87 children and young adults (with 238 pairs of proximal caries lesions radiographically extending into the inner half of the enamel [E2] or the outer third of the dentin [D1]) were randomly allocated to either 1 of 2 treatments. Test lesions were infiltrated, and a mock treatment was performed in control lesions by 5 German private practitioners. All patients received instructions for a noncariogenic diet, flossing and fluoridation, and individualized noninvasive interventions. The primary outcome was radiographic lesion progression (pairwise comparison) evaluated independently by 2 evaluators who were blinded to treatment allocation. After approximately 10 mo (mean ± SD 307 ± 43 d), 92 of 148 lesion pairs in 24 of 38 treated patients who were at high caries risk could be re-evaluated clinically as well as radiographically using individualized bitewing holders, as at baseline; 186 of 204 lesion pairs in 70 of 77 patients (35 of 38 high-risk patients) could be evaluated after 18 mo (mean 542 ± 110 d). No unwanted effects were observed. After 10 mo, progression was recorded in 2 of 92 test lesions (2%) and in 22 of 92 control lesions (24%) (P= 0.001, McNemar/Obuchowski test; relative risk reduction, 91; 95% confidence interval, 62%-98%). After 18 mo, lesion progression was recorded in all included patients in 10 of 186 test lesions (5%) and in 58 of 186 control lesions (31%) (P< 0.001; relative risk reduction, 83; 95% confidence interval, 67%-91%). Thus, resin infiltration seems to be

  11. Childhood leukemia and residential proximity to industrial and urban sites

    SciTech Connect

    García-Pérez, Javier; López-Abente, Gonzalo; Gómez-Barroso, Diana; Morales-Piga, Antonio; Pardo Romaguera, Elena; Tamayo, Ibon; Fernández-Navarro, Pablo; and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  12. Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes

    PubMed Central

    Rosenfeld, Jill A; Traylor, Ryan N; Schaefer, G Bradley; McPherson, Elizabeth W; Ballif, Blake C; Klopocki, Eva; Mundlos, Stefan; Shaffer, Lisa G; Aylsworth, Arthur S

    2012-01-01

    Chromosomal band 1q21.1 can be divided into two distinct regions, proximal and distal, based on segmental duplications that mediate recurrent rearrangements. Microdeletions and microduplications of the distal region within 1q21.1, which are susceptibility factors for a variety of neurodevelopmental phenotypes, have been more extensively studied than proximal microdeletions and microduplications. Proximal microdeletions are known as a susceptibility factor for thrombocytopenia-absent radius (TAR) syndrome, but it is unclear if these proximal microdeletions have other phenotypic consequences. Therefore, to elucidate the clinical significance of rearrangements of the proximal 1q21.1 region, we evaluated the phenotypes in patients identified with 1q21.1 rearrangements after referral for clinical microarray testing. We report clinical information for 55 probands with copy number variations (CNVs) involving proximal 1q21.1: 22 microdeletions and 20 reciprocal microduplications limited to proximal 1q21.1 and 13 microdeletions that include both the proximal and distal regions. Six individuals with proximal microdeletions have TAR syndrome. Three individuals with proximal microdeletions and two individuals with larger microdeletions of proximal and distal 1q21.1 have a ‘partial' TAR phenotype. Furthermore, one subject with TAR syndrome has a smaller, atypical deletion, narrowing the critical deletion region for the syndrome. Otherwise, phenotypic features varied among individuals with these microdeletions and microduplications. The recurrent, proximal 1q21.1 microduplications are enriched in our population undergoing genetic testing compared with control populations. Therefore, CNVs in proximal 1q21.1 can be a contributing factor for the development of abnormal phenotypes in some carriers. PMID:22317977

  13. Developing a Promotional Video

    ERIC Educational Resources Information Center

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  14. Factors affecting minority population proximity to hazardous facilities

    SciTech Connect

    Nieves, L.A.; Nieves, A.L. |

    1995-04-01

    Disproportionate exposure of minority groups to environmental hazards has been attributed to ``environmental racism`` by some authors, without systematic investigation of the factors underlying this exposure pattern. This study examines regional differences in the proximity of African-Americans, Hispanics, Asians, and non-Hispanic Whites to a broad range of facility types and explores the effects of urban and income factors. A statistically significant inverse relationship is found between the percentage of non-Hispanic Whites and virtually all facility categories in all regions. Except for Hispanics in the South, all such associations for minority groups show a direct relationship, though some are nonsignificant. The geographic concentration of facilities is more closely tied to urbanization than to economic factors. Controlling for both urban and economic factors, minority population concentration is still a significant explanatory variable for some facility types in some regions. This finding is most consistent for African-Americans.

  15. Variable reluctance proximity sensors for cryogenic valve position indication

    NASA Technical Reports Server (NTRS)

    Cloyd, R. A.

    1982-01-01

    A test was conducted to determine the performance of a variable reluctance proximity sensor system when installed in a space shuttle external tank vent/relief valve. The sensors were used as position indicators. The valve and sensors were cycled through a series of thermal transients; while the valve was being opened and closed pneumatically, the sensor's performance was being monitored. During these thermal transients, the vent valve was cooled ten times by liquid nitrogen and two times by liquid hydrogen. It was concluded that the sensors were acceptable replacements for the existing mechanical switches. However, the sensors need a mechanical override for the target similar to what is presently used with the mechanical switches. This override could insure contact between sensor and target and eliminate any problems of actuation gap growth caused by thermal gradients.

  16. Fundamental Proximity Effects in Focused electron Beam Induced Deposition

    SciTech Connect

    Plank, Harald; Smith, Daryl; Haber, Thomas; Rack, Philip D; Hofer, Ferdinand

    2012-01-01

    Fundamental proximity effects for electron beam induced deposition processes on nonflat surfaces were studied experimentally and via simulation. Two specific effects were elucidated and exploited to considerably increase the volumetric growth rate of this nanoscale direct write method: (1) increasing the scanning electron pitch to the scale of the lateral electron straggle increased the volumetric growth rate by 250% by enhancing the effective forward scattered, backscattered, and secondary electron coefficients as well as by strong recollection effects of adjacent features; and (2) strategic patterning sequences are introduced to reduce precursor depletion effects which increase volumetric growth rates by more than 90%, demonstrating the strong influence of patterning parameters on the final performance of this powerful direct write technique.

  17. Automobile proximity and indoor residential concentrations of BTEX and MTBE

    SciTech Connect

    Corsi, Dr. Richard; Morandi, Dr. Maria; Siegel, Dr. Jeffrey; Hun, Diana E

    2011-01-01

    Attached garages have been identified as important sources of indoor residential air pollution. However, the literature lacks information on how the proximity of cars to the living area affects indoor concentrations of gasoline-related compounds, and the origin of these pollutants. We analyzed data from the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study and evaluated 114 residences with cars in an attached garage, detached garage or carport, or without cars. Results indicate that homes with cars in attached garages were affected the most. Concentrations in homes with cars in detached garages and residences without cars were similar. The contribution from gasoline-related sources to indoor benzene and MTBE concentrations appeared to be dominated by car exhaust, or a combination of tailpipe and gasoline vapor emissions. Residing in a home with an attached garage could lead to benzene exposures ten times higher than exposures from commuting in heavy traffic.

  18. Computer vision for dual spacecraft proximity operations -- A feasibility study

    NASA Astrophysics Data System (ADS)

    Stich, Melanie Katherine

    A computer vision-based navigation feasibility study consisting of two navigation algorithms is presented to determine whether computer vision can be used to safely navigate a small semi-autonomous inspection satellite in proximity to the International Space Station. Using stereoscopic image-sensors and computer vision, the relative attitude determination and the relative distance determination algorithms estimate the inspection satellite's relative position in relation to its host spacecraft. An algorithm needed to calibrate the stereo camera system is presented, and this calibration method is discussed. These relative navigation algorithms are tested in NASA Johnson Space Center's simulation software, Engineering Dynamic On-board Ubiquitous Graphics (DOUG) Graphics for Exploration (EDGE), using a rendered model of the International Space Station to serve as the host spacecraft. Both vision-based algorithms proved to attain successful results, and the recommended future work is discussed.

  19. Proximal Hamstring Tendinopathy: Clinical Aspects of Assessment and Management.

    PubMed

    Goom, Thomas S H; Malliaras, Peter; Reiman, Michael P; Purdam, Craig R

    2016-06-01

    Synopsis Proximal hamstring tendinopathy (PHT) typically manifests as deep buttock pain at the hamstring common origin. Both athletic and nonathletic populations are affected by PHT. Pain and dysfunction are often long-standing and limit sporting and daily functions. There is limited evidence regarding diagnosis, assessment, and management; for example, there are no randomized controlled trials investigating rehabilitation of PHT. Some of the principles of management established in, for example, Achilles and patellar tendinopathy would appear to apply to PHT but are not as well documented. This narrative review and commentary will highlight clinical aspects of assessment and management of PHT, drawing on the available evidence and current principles of managing painful tendinopathy. The management outline presented aims to guide clinicians as well as future research. J Orthop Sports Phys Ther 2016;46(6):483-493. Epub 15 Apr 2016. doi:10.2519/jospt.2016.5986. PMID:27084841

  20. Fundamental proximity effects in focused electron beam induced deposition.

    PubMed

    Plank, Harald; Smith, Daryl A; Haber, Thomas; Rack, Philip D; Hofer, Ferdinand

    2012-01-24

    Fundamental proximity effects for electron beam induced deposition processes on nonflat surfaces were studied experimentally and via simulation. Two specific effects were elucidated and exploited to considerably increase the volumetric growth rate of this nanoscale direct write method: (1) increasing the scanning electron pitch to the scale of the lateral electron straggle increased the volumetric growth rate by 250% by enhancing the effective forward scattered, backscattered, and secondary electron coefficients as well as by strong recollection effects of adjacent features; and (2) strategic patterning sequences are introduced to reduce precursor depletion effects which increase volumetric growth rates by more than 90%, demonstrating the strong influence of patterning parameters on the final performance of this powerful direct write technique. PMID:22181556

  1. Optical proximity correction: A cross road of data flows

    NASA Astrophysics Data System (ADS)

    De Bisschop, Peter

    2016-06-01

    This paper reviews the various data flows that occur in the generation and verification of optical proximity correction (OPC) for an optical lithography photomask. First we review the models that are or can be used in the OPC model-calibration flow, with some emphasis on those models that are not yet standard practice. Through an efficient selection of calibration structures, the data amounts needed for model calibrations can be usually kept reasonably small. This is much less the case in the OPC verification step (computationally first and on-wafer afterwards), where data volumes can be very large. Especially the inspection of printed test wafer, where the printability of large number of structures needs to be assessed throughout the intended process window, currently presents important challenges as “hotspot” detection and printability quantification needs to be combined with a short turn-around time. We will discuss some of the approaches that are being employed to deal with these conflicting requirements.

  2. Granger causality stock market networks: Temporal proximity and preferential attachment

    NASA Astrophysics Data System (ADS)

    Výrost, Tomáš; Lyócsa, Štefan; Baumöhl, Eduard

    2015-06-01

    The structure of return spillovers is examined by constructing Granger causality networks using daily closing prices of 20 developed markets from 2nd January 2006 to 31st December 2013. The data is properly aligned to take into account non-synchronous trading effects. The study of the resulting networks of over 94 sub-samples revealed three significant findings. First, after the recent financial crisis the impact of the US stock market has declined. Second, spatial probit models confirmed the role of the temporal proximity between market closing times for return spillovers, i.e. the time distance between national stock markets matters. Third, a preferential attachment between stock markets exists, i.e. the probability of the presence of spillover effects between any given two markets increases with their degree of connectedness to others.

  3. Residential Proximity to Environmental Hazards and Adverse Health Outcomes

    PubMed Central

    Maantay, Juliana A.; Chakraborty, Jayajit

    2011-01-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  4. Rendezvous, proximity operations and capture quality function deployment report

    NASA Technical Reports Server (NTRS)

    Lamkin, Stephen L. (Editor)

    1991-01-01

    Rendezvous, Proximity Operations, and Capture (RPOC) is a missions operations area which is extremely important to present and future space initiatives and must be well planned and coordinated. To support this, a study team was formed to identify a specific plan of action using the Quality Function Deployment (QFD) process. This team was composed of members from a wide spectrum of engineering and operations organizations which are involved in the RPOC technology area. The key to this study's success is an understanding of the needs of potential programmatic customers and the technology base available for system implementation. To this end, the study team conducted interviews with a variety of near term and future programmatic customers and technology development sponsors. The QFD activity led to a thorough understanding of the needs of these customers in the RPOC area, as well as the relative importance of these needs.

  5. Induced gap in topological materials from the superconducting proximity effect

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Cole, William

    Topological superconductivity has been of considerable interest lately, with several proposed experimental realizations in solid state systems. A heterostructure of s-wave superconductor and 3D topological insulator is one of the more promising platforms, with topological superconductivity realized on the ''naked'' surface of the topological insulator through the superconducting proximity effect. We theoretically study the induced superconducting gap on the naked surface. Adjusting the Fermi level above the bulk gap (which is the case in experiments), our results for the induced superconducting gap are in agreement with that probed in thin topological insulators (<10nm) in the experiments (Nat. Phys. 10, 943-950 (2014) and Phys. Rev. Lett. 112, 217001 (2014)). We further predict the gap in thick topological insulators (>10nm). This work is supported by LPS-MPO-CMTC, Microsoft Q, and JQI-NSF-PFC.

  6. Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply

    PubMed Central

    O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

    2014-01-01

    Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components. PMID:25487822

  7. Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply

    NASA Astrophysics Data System (ADS)

    O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

    2014-12-01

    Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components.

  8. Solute-Solvent Energetics Based on Proximal Distribution Functions.

    PubMed

    Ou, Shu-Ching; Pettitt, B Montgomery

    2016-08-25

    We consider the hydration structure and thermodynamic energetics of solutes in aqueous solution. On the basis of the dominant local correlation between the solvent and the chemical nature of the solute atoms, proximal distribution functions (pDF) can be used to quantitatively estimate the hydration pattern of the macromolecules. We extended this technique to study the solute-solvent energetics including the van der Waals terms representing excluded volume and tested the method with butane and propanol. Our results indicate that the pDF-reconstruction algorithm can reproduce van der Waals solute-solvent interaction energies to useful kilocalorie per mole accuracy. We subsequently computed polyalanine-water interaction energies for a variety of conformers, which also showed agreement with the simulated values. PMID:27095487

  9. Proximal and point detection of contaminated surfaces using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Guicheteau, Jason A.; Christesen, Steven D.; Tripathi, Ashish; Emmons, Erik D.; Wilcox, Phillip G.; Emge, Darren K.; Pardoe, Ian J.; Fountain, Augustus W., III

    2011-11-01

    We are actively investigating the use of Raman spectroscopy for proximal standoff detection of chemicals and explosive materials on surfaces. These studies include Raman Chemical Imaging of contaminated fingerprints for forensic attribution and the assessments of commercial handheld or portable Raman instruments operating with near-infrared (IR) as well as ultraviolet (UV) laser excitation specifically developed for on-the-move reconnaissance of chemical contamination. As part of these efforts, we have measured the Raman cross sections of chemical agents, toxic industrial chemicals, and explosives from the UV to NIR. We have also measured and modeled the effect interrogation angle has on the Raman return from droplets on man-made surfaces. Realistic droplet distributions have been modeled and tested against variations in surface scan patterns and laser spot size for determining the optimum scan characteristics for detection of relevant surface contamination.

  10. Retroperitoneal Laparoscopic Ureterolithotomy for Proximal Ureteral Calculi in Selected Patients

    PubMed Central

    Hu, Qingfeng; Ding, Weihong; Gou, Yuancheng; Ho, Yatfaat; Xu, Ke; Gu, Bin; Sun, Chuanyu; Xia, Guowei; Ding, Qiang

    2014-01-01

    Objectives. To summarize our experience of retroperitoneal laparoscopic ureterolithotomy for ureteral calculi and evaluate the safety and efficiency of this procedure. Methods. We conducted a retrospective analysis of 197 patients with proximal ureteral calculi who accepted retroperitoneal laparoscopic ureterolithotomy from June 2005 to June 2014. Results. All procedures were performed successfully and the mean operating time and estimated blood loss were 87 min and 64 mL. The clearance rate was 98.5% and the rates of urine leak and ureteral stricture were 2.5% and 1.0%. Conclusions. Retroperitoneal laparoscopic ureterolithotomy is a safe and effective procedure for patients with complex stones or anatomic abnormalities, and, with experience of high volume series, it is also a reasonable choice as the primary treatment for such selected patients. PMID:25548791

  11. Optical proximity correction using a multilayer perceptron neural network

    NASA Astrophysics Data System (ADS)

    Luo, Rui

    2013-07-01

    Optical proximity correction (OPC) is one of the resolution enhancement techniques (RETs) in optical lithography, where the mask pattern is modified to improve the output pattern fidelity. Algorithms are needed to generate the modified mask pattern automatically and efficiently. In this paper, a multilayer perceptron (MLP) neural network (NN) is used to synthesize the mask pattern. We employ the pixel-based approach in this work. The MLP takes the pixel values of the desired output wafer pattern as input, and outputs the optimal mask pixel values. The MLP is trained with the backpropagation algorithm, with a training set retrieved from the desired output pattern, and the optimal mask pattern obtained by the model-based method. After training, the MLP is able to generate the optimal mask pattern non-iteratively with good pattern fidelity.

  12. [Vascular injuries complicating osteosynthesis in proximal femur fractures].

    PubMed

    Manner, M; Rösch, B; Roy, K

    1999-03-01

    While there are quite a number of reports on vascular injuries complicating hip arthropasty by acetabular component screw fixation, retractor tip pressure or extruding bone cement, the incidence of deep femoral vessel injuries in operative fixation of proximal femoral fractures is comparatively seldom described. We report on two patients with per- and subtrochanteric femoral fractures who sustained injuries of deep femoral artery branches during the implantation of a dynamic hip screw (DHS) and a dynamic condylar screw (DCS), which resulted in a massive thigh hematoma and a fist-size pseudoaneurysm respectively and necessitated surgical intervention in either case. We blame these vascular injuries on the pressure of Hohmann retractors exposing the femoral bone or on the drilling of boreholes for plate attachment. After discussing various operative procedures, we conclude that intramedullar implants are safer than plates with regard to potential vascular complications. PMID:10232039

  13. Proximity fingerprint of s{plus_minus} superconductivity.

    SciTech Connect

    Koshelev, A. E.; Stanev, V.

    2011-01-01

    We suggest a straightforward and unambiguous test to identify possible opposite signs of the superconducting order parameter in different bands proposed for iron-based superconductors (s{sub {+-}}-state). We consider the proximity effect in a weakly coupled sandwich composed of a s{sub {+-}}-superconductor and a thin layer of the s-wave superconductor. In such system the s-wave order parameter is coupled differently with different s{sub {+-}}-gaps and it typically aligns with one of these gaps. This forces the other s{sub {+-}}-gap to be anti-aligned with the s-wave gap. In such situation the aligned band induces a peak in the s-wave density of states (DoS), while the anti-aligned band induces a dip. Observation of such contact-induced negative feature in the s-wave DoS would provide a definite proof for s{sub {+-}}-superconductivity.

  14. Orion Rendezvous, Proximity Operations, and Docking Design and Analysis

    NASA Technical Reports Server (NTRS)

    D'Souza, Christopher; Hanak, F. Chad; Spehar, Pete; Clark, Fred D.; Jackson, Mark

    2007-01-01

    The Orion vehicle will be required to perform rendezvous, proximity operations, and docking with the International Space Station (ISS) and the Earth Departure Stage (EDS)/Lunar Landing Vehicle (LLV) stack in Low Earth Orbit (LEO) as well as with the Lunar Landing Vehicle in Low Lunar Orbit (LLO). The RPOD system, which consists of sensors, actuators, and software is being designed to be flexible and robust enough to perform RPOD with different vehicles in different environments. This paper will describe the design and the analysis which has been performed to date to allow the vehicle to perform its mission. Since the RPOD design touches on many areas such as sensors selection and placement, trajectory design, navigation performance, and effector performance, it is inherently a systems design problem. This paper will address each of these issues in order to demonstrate how the Orion RPOD has been designed to accommodate and meet all the requirements levied on the system.

  15. Residential proximity to high voltage transmission lines and depressive symptomatology

    SciTech Connect

    McMahan, S.G.

    1992-01-01

    A number of epidemiological studies indicate an association between depression and proximity to high voltage transmission lines. These studies have been criticized, however, for using surrogate measures of electromagnetic fields (EMFs) and unstandardized measures of depression. In an effort to overcome these limitations, the Center for Epidemiological Studies Depression (CES-D) scale was administered to 152 women living either adjacent to a transmission line or one block away. Results indicate that homes adjacent to the transmission lines have an average EMF level of 4.86 milligauss at their front door and those one block away have an average of 0.68 milligauss. There was no significant difference in CES-D scores between the groups, controlling for demographic variables. There appeared to be an increase in other health effects, including cancer and miscarriages, but these findings were preliminary and need further investigation.

  16. Xanthogranulomatous Osteomyelitis of Proximal Femur Masquerading as Benign Bone Tumor.

    PubMed

    Singh, Shailendra; Batra, Sahil; Maini, Lalit; Gautam, Virender Kumar

    2015-08-01

    We describe a case of xanthogranulomatous osteomyelitis (XO) of the proximal femur in a 65-year-old woman who presented with pain of 6 months' duration in the right hip. Plain radiographs showed a lytic well-defined lesion in the right peritrochanteric region suggestive of a benign neoplastic etiology. The gross and histopathologic examination of the curettage specimen was consistent with XO. Xanthogranulomatous osteomyelitis is a rare chronic inflammatory process that is characterized by the presence of a large number of lipid-containing macrophages with an admixture of lymphocytes, plasma cells, and neutrophils. Gross and radiologic examination of this entity can mimic malignancy, and differentiation should be confirmed by histopathologic evaluation. To the best of our knowledge, XO of the femur has not been reported in the English-language literature. The rarity of this condition and its resemblance to bone tumors form the basis of this case report. PMID:26251942

  17. Extraction of spatial proximity patterns by concept generalization

    SciTech Connect

    Knorr, E.M.; Ng, R.T.

    1996-12-31

    We study the spatial data mining problem of how to extract a special type of proximity relationship-namely that of distinguishing two clusters of points based on the types of their neighboring features. The points in the clusters may represent houses on a map, and the features may represent spatial entities such as schools, parks, golf courses, etc. Classes of features are organized into concept hierarchies. We develop algorithm GenDis which uses concept generalization to identify the distinguishing features or concepts which serve as discriminators. Furthermore, we study the issue of which discriminators are {open_quotes}better{close_quotes} than others by introducing the notion of maximal discriminators, and by using a ranking system to quantitatively weigh maximal discriminators from different concept hierarchies.

  18. Endovascular Treatment of Proximal Anastomotic Aneurysms After Aortic Prosthetic Reconstruction

    SciTech Connect

    Tiesenhausen, Kurt; Hausegger, Klaus A.; Tauss, Josef; Amann, Wilfried; Koch, Guenter

    2001-01-15

    Purpose: To describe the efficacy and value of endovascular stent-grafts for the treatment of aortic anastomotic pseudoaneurysms.Methods: Three patients with proximal aortic anastomotic pseudoaneurysms 8-15 years after prosthetic reconstruction were treated by transfemoral stent-graft implantation. In two patients the pseudoaneurysms were excluded by Talent prostheses [tube graft (n = 1), bifurcated graft (n = 1)]. In one patient an uni iliac Zenith stent-graft was implanted and an extra-anatomic crossover bypass for revascularization of the contralateral lower extremity was performed.Results: All procedures were successful with primary exclusion of the pseudoaneurysms. During the follow-up (mean 16 months) one endoleak occurred due to migration of the tube stent-graft. The endoleak was sealed successfully by implanting an additional bifurcated stent-graft.Conclusion: Stent-graft exclusion of aortic pseudoaneurysms offers a minimally invasive and safe alternative to open surgical reconstruction.

  19. Endovascular treatment of proximal arsastomotic aneurysms after aortic prosthetic reconstruction

    SciTech Connect

    Tiesenhausen, Kurt; Hausegger, Klaus A.; Tauss, Josef; Amann, Wilfried; Koch, Guenter

    2001-01-15

    Purpose: To describe the efficacy and value of endovascular stent-grafts for the treatment of aortic anastomotic pseudo-aneurysms.Methods: Three patients with proximal aortic anastomotic pseudoaneurysms 8-15 years after prosthetic reconstruction were treated by transfemoral stent-graft implantation. In two patients the pseudoaneurysms were excluded by Talent prostheses [tube graft (n=1), bifurcated graft (n=s1)]. In one patient an uniiliac Zenith stent-graft was implanted and an extra-anatomic crossover bypass for revascularization of the contralateral lower extremity was performed.Results: All procedures were successful with primary exclusion of the pseudoaneurysms. During the follow-up (mean 16 months) one endoleak occurred due to migration of the tube stent-graft. The endoleak was sealed successfully by implanting an additional bifurcated stent-graft.Conclusion: Stent-graft exclusion of aortic pseudoaneurysms offers a minimally invasive and safe alternative to open surgical reconstruction.

  20. Anomalous magnetization reversal due to proximity effect of antiphase boundaries

    NASA Astrophysics Data System (ADS)

    Sofin, R. G. S.; Wu, Han-Chun; Shvets, I. V.

    2011-12-01

    Here we report anomalous double switching hysteresis loop and high coercivity (˜0.1 T) in Fe3O4(110) thin films. Our analytical model based on spin chains confined within small antiphase boundary domains (APBDs) suggests a significant proximity effect of antiferromagnetic antiphase boundaries (APBs). Furthermore, the calculated domain size (D) follows the well-known scaling relation D=Ct. The results suggest that the interface exchange coupling between neighboring magnetic domains through antiferromagnetic APBs is responsible for the double switching hysteresis. Our findings could help advance the studies of anomalous properties of magnetic materials originating from growth defects. This effect can be utilized for the tunability of exchange bias in devices.